Doctor of Philosophy

dissertationTreatment adherence remains a major challenge in tuberculosis (TB) control. Mobile phone text messaging is a promising tool to support TB treatment adherence. The purpose of this study was to develop a text messaging intervention to promote TB treatment adherence, assess feasibility and acceptability, and to explore initial efficacy. A collaborative team of clinicians, administrators and patients in treatment developed the intervention. Content analysis, based on the Information-Motivation-Behavioral Skills (IMB) model, guided educational message selection. To identify considerations for a larger trial a socio-technical evaluation model adapted from Conford, and Barber and associates was applied. The intervention was implemented as a mixed-method, randomized controlled pilot-study at a public pulmonary-specialized hospital in Argentina. Patients newly diagnosed with TB who were18 or older, without drug resistance or HIV, and had access to a mobile phone were recruited. Participants were randomized to usual care plus either medication calendar (n=19) or text messaging intervention (n=18) for the first 2 months of treatment. Data were obtained through interviews, field notes, self-reported adherence, sputum microscopy, and treatment outcomes. Most potential participants had access to mobile phones and knew how to send a text, supporting feasibility of the intervention. The majority of the participants (60%) indicated not being adequately informed about disease or treatment. Participants identified themes of feeling cared for, responsible for their treatment and valued the option to ask questions and receive quick answers. Texting group participants reported adherence 77% of the days (SD 23.5, range 22-100), whereas only 53% in the control group returned calendars. Sputum conversion and treatment outcomes were similar in both groups. Considerations for conducting a larger trial included reducing cost, improving the automated features, and strengthening capacity to return patients to treatment. A collaborative approach and application of the IMB model to guide development was supported. Overall the texting intervention was well accepted and feasible, daily reporting was superior, and adherence was monitored in real time. Although there was not clear evidence that the texting intervention was more efficacious, feasibility and acceptability results suggest that there is value in assessing this interactive intervention in a larger-scale study

Effects of mindfulness-based cognitive therapy on mental disorders: a systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: Mindfulness-based cognitive therapy (MBCT) is a programme developed to prevent depression relapse, but has been applied for other disorders. Our objective was to systematically review and meta-analyse the evidence on the effectiveness and safety of MBCT for the treatment of mental disorders. METHODS: Searches were completed in CENTRAL, MEDLINE, EMBASE, LILACS, PsychINFO, and PsycEXTRA in March 2011 using a search strategy with the terms 'mindfulness-based cognitive therapy', 'mindfulness', and 'randomised controlled trials' without time restrictions. Selection criteria of having a randomised controlled trial design, including patients diagnosed with mental disorders, using MBCT according to the authors who developed MBCT and providing outcomes that included changes in mental health were used to assess 608 reports. Two reviewers applied the pre-determined selection criteria and extracted the data into structured tables. Meta-analyses and sensitivity analyses were completed. RESULTS: Eleven studies were included. Most of them evaluated depression and compared additive MBCT against usual treatment. After 1 year of follow-up MBCT reduced the rate of relapse in patients with three or more previous episodes of depression by 40% (5 studies, relative risk [95% confidence interval]: 0.61 [0.48, 0.79]). Other meta-analysed outcomes were depression and anxiety, both with significant results but unstable in sensitivity analyses. Methodological quality of the reports was moderate. CONCLUSION: Based on this review and meta-analyses, MBCT is an effective intervention for patients with three or more previous episodes of major depression

Smartphone Applications to Support Tuberculosis Prevention and Treatment: Review and Evaluation

Background: Tuberculosis (TB) remains a major global health problem and is the leading killer due to a single infectious disease. Mobile health (mHealth)–based tools such as smartphone apps have been suggested as tools to support TB control efforts (eg, identification, contact tracing, case management including patient support). Objective: The purpose of this review was to identify and assess the functionalities of mobile apps focused on prevention and treatment of TB. Methods: We searched 3 online mobile app stores. Apps were included if they were focused on TB and were in English, Spanish, or Portuguese. For each included app, 11 functionalities were assessed (eg, inform, instruct, record), and searches were conducted to identify peer-review publications of rigorous testing of the available apps. Results: A total of 1332 potentially relevant apps were identified, with 24 meeting our inclusion criteria. All of the apps were free to download, but 7 required login and password and were developed for specific clinics, regional sites, or research studies. Targeted users were mainly clinicians (n=17); few (n=4) apps were patient focused. Most apps (n=17) had 4 or fewer functions out of 11 (range 1-6). The most common functionalities were inform and record (n=15). Although a number of apps were identified with various functionalities to support TB efforts, some had issues such as incorrect spelling and grammar, inconsistent responses to data entry, problems with crashing, or links to features that had no data. Of more concern, some apps provided potentially harmful information to patients, such as links to natural remedies for TB and natural healers. One-third of the apps (8/24) had not been updated for more than a year and may no longer be supported. Peer-reviewed publications were identified for only two of the included apps. In the gray literature (not found in the app stores), three TB-related apps were identified as in progress, being launched, or tested. Conclusions: Apps identified for TB prevention and treatment had minimal functionality, primarily targeted frontline health care workers, and focused on TB information (eg, general information, guidelines, and news) or data collection (eg, replace paper-based notification or tracking). Few apps were developed for use by patients and none were developed to support TB patient involvement and management in their care (eg, follow-up alerts/reminders, side effects monitoring) or improve interaction with their health care providers, limiting the potential of these apps to facilitate patient-centered care. Our evaluation shows that more refined work is needed to be done in the area of apps to support patients with active TB. Involving TB patients in treatment in the design of these apps is recommended

mHealth intervention development to support patients with active tuberculosis

Background: Mobile Health (mHealth) based interventions have been increasingly used to improve a broad range of health outcomes. However, few researchers have reported on the process or the application of theory to guide the development of mHealth based interventions, or specifically for tuberculosis (TB) treatment management. Aims: To describe the steps, process, and considerations in developing a text messaging-based intervention to promote treatment adherence and provide support to patients with active TB. Methods: Traditional qualitative techniques, including semi-structured interviews, field notes, content analysis, iterative coding, and thematic analysis, were used to design and document the intervention development with a multidisciplinary team of researchers, clinicians, administrators, and patients who were in active TB treatment. The Information-Motivation-Behavioral Skills (IMB) model was used to guide the coding scheme for content analysis of patient-directed TB educational material and intervention development. Results: The development steps included: a) establishing intervention components, including justifications, considerations, timing and frequency of components; b) developing educational messages, including cultural adaption, text or short message service (SMS) formatting, and prioritizing message delivery order; and c) determining implementation protocol. A set of 16 IMB-based messages were developed for the educational component. Final intervention development was achieved in 3 months. Conclusion: A collaborative approach and application of a theory to guide the intervention design and development is supported. Although a collaborative approach was more time consuming, it resulted in a more responsive, culturally appropriate, and comprehensive intervention. Considerations for developing a text messaging based intervention are provided and may serve as a guide for similar interventions. Further empirical evidence is needed for applying the IMB model for adherence-promotion in TB efforts

Glacial lakes of the Central and Patagonian Andes

The prevalence and increased frequency of high-magnitude Glacial Lake Outburst Floods (GLOFs) in the Chilean and Argentinean Andes suggests this region will be prone to similar events in the future as glaciers continue to retreat and thin under a warming climate. Despite this situation, monitoring of glacial lake development in this region has been limited, with past investigations only covering relatively small regions of Patagonia. This study presents new glacial lake inventories for 1986, 2000 and 2016, covering the Central Andes, Northern Patagonia and Southern Patagonia. Our aim was to characterise the physical attributes, spatial distribution and temporal development of glacial lakes in these three sub-regions using Landsat satellite imagery and image datasets available in Google Earth and Bing Maps. Glacial lake water volume was also estimated using an empirical area-volume scaling approach. Results reveal that glacial lakes across the study area have increased in number (43%) and areal extent (7%) between 1986 and 2016. Such changes equate to a glacial lake water volume increase of 65?km3 during the 30-year observation period. However, glacial lake growth and emergence was shown to vary sub-regionally according to localised topography, meteorology, climate change, rate of glacier change and the availability of low gradient ice areas. These and other factors are likely to influence the occurrence of GLOFs in the future. This analysis represents the first large-scale census of glacial lakes in Chile and Argentina and will allow for a better understanding of lake development in this region, as well as, providing a basis for future GLOF risk assessments.authorsversionPeer reviewe

Comparison of a User-Centered Design, Self-Management App to Existing mHealth Apps for Persons Living With HIV

Background: There is preliminary evidence that mobile health (mHealth) apps are feasible, attractive, and an effective platform for the creation of self-management tools for persons living with HIV (PLWH). As a foundation for the current study, we conducted formative research using focus groups, participatory design sessions, and usability evaluation methods to inform the development of a health management app for PLWH. The formative research resulted in identification of the following functional requirements of a mHealth app for self-management: (1) communication between providers and peers, (2) medication reminders, (3) medication log, (4) lab reports, (5) pharmacy information, (6) nutrition and fitness, (7) resources (eg, social services, substance use, video testimonials), (8) settings, and (9) search function. Objective: The purpose of this study was to conduct an ecological review of the existing apps for PLWH and to compare the functionality of existing apps with the app specifications identified in our formative work. Methods: We searched two mobile app stores (Google Play and iTunes) and found a total of 5606 apps. We reviewed the apps, narrowed our search terms, and found a total of 112 apps. Of these, we excluded 97 (86.6%) apps that were either not in English (10/112, 8.9%), not HIV focused (32/112, 28.9%), or focused only on HIV prevention (2/112, 7.8%); targeted health care providers (26/112, 23.2%); provided information only on conference schedules and events (7/112, 6.3%), fundraisers (7/112, 6.3%), specific clinics (7/112, 6.3%), international or narrow local resources (3/112, 2.7%); or were identified in the first search but were no longer on the market at the next review (4/112, 3.6%). The 15 apps meeting inclusion criteria were then evaluated for inclusion of the nine functionalities identified in our earlier work. Results: Of the 15 apps that we included in our final review, none had all of the functionalities that were identified in our formative work. The apps that we identified included the following functionalities: communication with providers and/or peers (4/15, 27%), medication reminders (6/15, 40%), medication logs (7/15, 47%), lab reports (5/15, 33%), pharmacy information (4/15, 27%), resources (7/15, 47%), settings (11/15, 73%), and search function (6/15, 40%). No apps included nutrition or fitness information. Conclusions: Currently, there are only a small number of apps that have been designed for PLWH to manage their health. Of the apps that are currently available, none have all of the desired functionalities identified by PLWH and experts in our formative research. Findings from this work elucidate the need to develop and evaluate mobile apps that meet PLWH’s desired functional specifications

Cost of community-based human papillomavirus self-sampling in Peru : A micro-costing study

Declaration of Interest The authors declare no conflict of interest. Thomas Francis Jr. Fellowship provided funding for data collection. The Hope Project was funded by grants from Grand Challenges Canada (TTS-1812-21131), Uniting for Health Innovation, Global Initiative Against HPV and Cervical Cancer, University of Manitoba, and the John E. Fogarty International Center (5D43TW009375-05). None of the funders had any role in the study design, implementation, the process of data collection, data analysis, interpretation, or writing of the manuscript or the decision to submit it for publication. No authors have been paid to write this article by a pharmaceutical company or other agency. The authors were not precluded from accessing data in the study, and they accept responsibility to submit for publication. Publisher Copyright: © 2021 The Author(s)Background: Cost data of human papillomavirus (HPV) self-sampling programs from low-and-middle-income countries is limited. We estimated the total and unit costs associated with the Hope Project, a community-based HPV self-sampling social entrepreneurship in Peru. Methods: We conducted a micro-costing analysis from the program perspective to determine the unit costs of (1) recruitment/training of community women (Hope Ladies); (2) Hope Ladies distributing HPV self-sampling kits in their communities and the laboratory testing; and (3) Hope Ladies linking screened women with follow-up care. A procedural manual was used to identify the program's activities. A structured questionnaire and in-depth interviews were conducted with administrators to estimate the resource/time associated with activities. We obtained unit costs for each input previously identified from budgets and expenditure reports. Findings: From November 2018 to March 2020, the program recruited and trained 62 Hope Ladies who distributed 4,882 HPV self-sampling kits in their communities. Of the screened women, 586 (12%) tested HPV positive. The annual cost per Hope Lady recruited/trained was $147·51 (2018 USD). The cost per HPV self-sampling kit distributed/tested was$45·39, the cost per woman followed up with results was $55·64, and the cost per HPV-positive woman identified was$378·14. Personnel and laboratory costs represented 56·1% and 24·7% of the total programmatic cost, respectively. Interpretation: Our findings indicate that implementation of a community-based HPV self-sampling has competitive prices, which increases its likelihood to be feasible in Peru. Further economic evaluation is needed to quantify the incremental benefits of HPV self-sampling compared to more established options such as Pap tests. Funding: Thomas Francis Jr. Fellowship provided funding for data collection. The Hope Project was funded by grants from Grand Challenges Canada (TTS-1812-21131), Uniting for Health Innovation, Global Initiative Against HPV and Cervical Cancer, University of Manitoba, and the John E. Fogarty International Center (5D43TW009375-05).Peer reviewe

Evaluation of Women's Empowerment in a Community-Based Human Papillomavirus Self-Sampling Social Entrepreneurship Program (Hope Project) in Peru : A Mixed-Method Study

Funding Information: This work was supported by the University of Washington: School of Nursing, the United States Agency for International Development (USAID-DIV 7200AA19FA00001), Duke Universities Bass Connections project titled Analysis of Bringing Elements of Referral Services to Community Care, and GMaP Region 5 program of the Fred Hutch/University of Washington Cancer Consortium 3P30CA015704-46S5. Publisher Copyright: Copyright © 2022 Shin, Garcia, Dotson, Valderrama, Chiappe, Ramanujam, Krieger, Ásbjörnsdóttir, Barnabas, Iribarren and Gimbel.Introduction: Understanding community women's relational and financial empowerment in social entrepreneurship could be the key to scaling up community-based human papillomavirus (HPV) self-sampling programs in low- and middle-income countries. The Hope Project, social entrepreneurship in Peru, trains women (Hope Ladies) to promote HPV self-sampling among other women in their communities. This study aims to evaluate the Hope Ladies' relational and financial empowerment after participating in the program. Materials and Methods: We evaluated the Hope Ladies' experiences of empowerment in social entrepreneurship using a parallel convergent mixed methods design. The Hope Ladies participated in semi-structured in-depth interviews (n = 20) and an eight-questions five-point Likert scale survey that evaluated their relational (n = 19)/financial (n = 17) empowerment. The interview and the survey questions were developed using three empowerment frameworks: Kabeer's conceptual framework, International Center for Research on Women's economic empowerment indicators, and the Relational Leadership Theory. Deductive content analysis was used to evaluate the interviews with pre-determined codes and categories of empowerment. Descriptive statistics were used to analyze the survey results. Qualitative and quantitative data were integrated through a cross-case comparison of emergent themes and corresponding survey responses during the results interpretation. Results: All Hope Ladies reported experiencing increased empowerment in social entrepreneurship. Interviews: The women reported challenges and improvement in three categories of empowerment: (1) resources (balancing between household and Hope Lady roles, recognition from the community as a resource, camaraderie with other Hope Ladies); (2) agency (increased knowledge about reproductive health, improved confidence to express themselves, and ability to speak out against male-dominant culture); and (3) achievement (increased economic assets, improved ability to make financial decisions, and widened social network and capital, and technology skills development). Survey: All (100%) agreed/totally agreed an increase in social contacts, increased unaccompanied visits to a healthcare provider (86%), improved confidence in discussing reproductive topics (100%), improved ability to make household decisions about money (57% pre-intervention vs. 92% post-intervention). Conclusions: The Hope Ladies reported improved relational and financial empowerment through participating in community-based social entrepreneurship. Future studies are needed to elucidate the relationship between empowerment and worker retention/performance to inform the scale-up of HPV self-sampling social entrepreneurship programs.Peer reviewe

Social Class Differences in Secular Trends in Established Coronary Risk Factors over 20 Years: A Cohort Study of British Men from 1978–80 to 1998–2000

Background: Coronary heart disease (CHD) mortality in the UK since the late 1970s has declined more markedly among higher socioeconomic groups. However, little is known about changes in coronary risk factors in different socioeconomic groups. This study examined whether changes in established coronary risk factors in Britain over 20 years between 1978-80 and 1998-2000 differed between socioeconomic groups.Methods and Findings: A socioeconomically representative cohort of 7735 British men aged 40-59 years was followed-up from 1978-80 to 1998-2000; data on blood pressure (BP), cholesterol, body mass index (BMI) and cigarette smoking were collected at both points in 4252 survivors. Social class was based on longest-held occupation in middle-age. Compared with men in non-manual occupations, men in manual occupations experienced a greater increase in BMI (mean difference=0.33 kg/m(2); 95%CI 0.14-0.53; p for interaction=0.001), a smaller decline in non-HDL cholesterol (difference in mean change=0.18 mmol/l; 95%CI 0.11-0.25, p for interaction <= 0.0001) and a smaller increase in HDL cholesterol (difference in mean change=0.04 mmol/l; 95%CI 0.02-0.06, p for interaction <= 0.0001). However, mean systolic BP declined more in manual than non-manual groups (difference in mean change=3.6; 95%CI 2.1-5.1, p for interaction <= 0.0001). The odds of being a current smoker in 1978-80 and 1998-2000 did not differ between non-manual and manual social classes (p for interaction = 0.51).Conclusion: Several key risk factors for CHD and type 2 diabetes showed less favourable changes in men in manual occupations. Continuing priority is needed to improve adverse cardiovascular risk profiles in socially disadvantaged groups in the UK

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.