Jasmine Zia

Poly(2-alkylacrylic acid) polymers deliver molecules to the cytosol by pH-sensitive disruption of endosomal vesicles

The permeability barrier posed by cell membranes represents a challenge for the delivery of hydrophilic molecules into cells. We previously proposed that poly(2-alkylacrylic acid)s are endocytosed by cells into acidified vesicles and are there triggered by low pH to disrupt membranes and release the contents of endosomes/lysosomes to the cytosol. If this hypothesis is correct, these polymers could be valuable in drug-delivery applications. The present paper reports functional comparisons of a family of three poly(2-alkylacrylic acid)s. Poly(2-propylacrylic acid) (PPAA), poly(2-ethylacrylic acid) (PEAA) and poly(2-methylacrylic acid) (PMAA) were compared in red-blood-cell haemolysis assays and in a lipoplex (liposome-DNA complex) assay. We also directly examined the ability of these polymers to disrupt endosomes and lysosomes in cultured human cells. Our results show that: (i) unlike membrane-disruptive peptides, the endosomal-disruptive ability of poly(2-alkylacrylic acid)s cannot necessarily be predicted from their haemolytic activity at low pH, (ii) PPAA (but not PEAA or PMAA) potently facilitates gene transfection by cationic lipoplexes and (iii) endocytosed poly(2-alkylacrylic acid)s are triggered by luminal acidification to selectively disrupt endosomes (not lysosomes) and release their contents to the cytosol. These results will facilitate the rational design of future endosomal-disrupting polymers for drug delivery.

Boundary Negotiating Artifacts in Personal Informatics: Patient-Provider Collaboration with Patient-Generated Data

Patient-generated data is increasingly common in chronic disease care management. Smartphone applications and wearable sensors help patients more easily collect health information. However, current commercial tools often do not effectively support patients and providers in collaboration surrounding these data. This paper examines patient expectations and current collaboration practices around patient-generated data. We survey 211 patients, interview 18 patients, and re-analyze a dataset of 21 provider interviews. We find that collaboration occurs in every stage of self- tracking and that patients and providers create boundary negotiating artifacts to support the collaboration. Building upon current practices with patient-generated data, we use these theories of patient and provider collaboration to analyze misunderstandings and privacy concerns as well as identify opportunities to better support these collaborations. We reflect on the social nature of patient-provider collaboration to suggest future development of the stage-based model of personal informatics and the theory of boundary negotiating artifacts.

A framework for self-experimentation in personalized health

OBJECTIVE To describe an interdisciplinary and methodological framework for applying single case study designs to self-experimentation in personalized health. The authors examine the frameworks applicability to various health conditions and present an initial case study with irritable bowel syndrome (IBS). METHODS AND MATERIALS An in-depth literature review was performed to develop the framework and to identify absolute and desired health condition requirements for the application of this framework. The authors developed mobile application prototypes, storyboards, and process flows of the framework using IBS as the case study. The authors conducted three focus groups and an online survey using a human-centered design approach for assessing the frameworks feasibility. RESULTS All 6 focus group participants had a positive view about our framework and volunteered to participate in future studies. Most stated they would trust the results because it was their own data being analyzed. They were most concerned about confounds, nonmeaningful measures, and erroneous assumptions on the timing of trigger effects. Survey respondents (N = 60) were more likely to be adherent to an 8- vs 12-day study length even if it meant lower confidence results. DISCUSSION Implementation of the self-experimentation framework in a mobile application appears to be feasible for people with IBS. This framework can likely be applied to other health conditions. Considerations include the learning curve for teaching self-experimentation to non-experts and the challenges involved in operationalizing and customizing study designs. CONCLUSION Using mobile technology to guide people through self-experimentation to investigate health questions is a feasible and promising approach to advancing personalized health.

Supporting Patient-Provider Collaboration to Identify Individual Triggers using Food and Symptom Journals

Patient-generated data can allow patients and providers to collaboratively develop accurate diagnoses and actionable treatment plans. Unfortunately, patients and providers often lack effective support to make use of such data. We examine patient-provider collaboration to interpret patient-generated data. We focus on irritable bowel syndrome (IBS), a chronic illness in which particular foods can exacerbate symptoms. IBS management often requires patient-provider collaboration using a patients food and symptom journal to identify the patients triggers. We contribute interactive visualizations to support exploration of such journals, as well as an examination of patient-provider collaboration in interpreting the journals. Drawing upon individual and collaborative interviews with patients and providers, we find that collaborative review helps improve data comprehension and build mutual trust. We also find a desire to use tools like our interactive visualizations within and beyond clinic appointments. We discuss these findings and present guidance for the design of future tools.

Sleep measures predict next-day symptoms in women with irritable bowel syndrome.

STUDY OBJECTIVES Patients with irritable bowel syndrome (IBS) often report sleep disturbances. Previously, we have shown that self-reported sleep difficulties predicted exacerbations of next-day IBS symptoms, mood disturbance, and fatigue. The purpose of this study was to explore whether objectively measured sleep using actigraphy, as well as self-report, predicts next-day symptoms in women with IBS and to explore whether or not symptoms also predict self-report and objective sleep. METHODS Women aged 18-45 years with IBS were community-recruited (n = 24, mean age = 32 ± 8 years). Participants completed sleep and IBS symptom diaries for one menstrual cycle and wore Actiwatch-64 actigraphs for 7 days at home. Statistical analyses used generalized estimating equation (GEE) models. RESULTS Poorer self-reported sleep quality significantly (p < 0.05) predicted higher next-day abdominal pain, anxiety, and fatigue, but was not significant for gastrointestinal (GI) symptoms or depressed mood. Actigraphic sleep efficiency (SEF) significantly predicted worsening next-day anxiety and fatigue, but not abdominal pain, GI symptoms, or depressed mood. On temporally reversed analyses, none of the symptoms significantly predicted subsequent sleep, except that GI symptoms significantly predicted higher actigraphic sleep efficiency. CONCLUSION This small exploratory study supports previous findings that self-reported sleep disturbance predicted exacerbation of next-day symptoms in women with IBS and extends this relationship using an objective sleep measure. The study adds further evidence that sleep quality predicts subsequent IBS symptoms, but not the converse. The findings from this small study support the importance of additional longitudinal research to further understand the relationships between sleep and IBS.

Balance of Autonomic Nervous System Predicts Who Benefits from a Self-management Intervention Program for Irritable Bowel Syndrome.

Background/Aims To determine if potential biomarkers can be used to identify subgroups of people with irritable bowel syndrome (IBS) who will benefit the most or the least from a comprehensive self-management (CSM) intervention. Methods In a two-armed randomized controlled trial a CSM (n = 46) was compared to a usual care (n = 46) group with follow-up at 3 and 6 months post randomization. Biomarkers obtained at baseline included heart rate variability, salivary cortisol, interleukin-10 produced by unstimulated peripheral blood mononuclear cells, and lactulose/mannitol ratio. Linear mixed models were used to test whether these biomarkers predicted improvements in the primary outcomes including daily abdominal pain, Gastrointestinal Symptom score and IBS-specific quality of life. Results The nurse-delivered 8-session CSM intervention is more effective than usual care in reducing abdominal pain, reducing Gastrointestinal Symptom score, and enhancing quality of life. Participants with lower nighttime high frequency heart rate variability (vagal modulation) and increased low frequency/high frequency ratio (sympathovagal balance) had less benefit from CSM on abdominal pain. Salivary cortisol, IL-10, and lactulose/mannitol ratio were not statistically significant in predicting CSM benefit. Baseline symptom severity interacts with treatment, namely the benefit of CSM is greater in those with higher baseline symptoms. Conclusions Cognitively-focused therapies may be less effective in reducing abdominal pain in IBS patients with higher sympathetic tone. Whether this a centrally-mediated patient characteristic or related to heightened arousal remains to be determined.

TummyTrials: A Feasibility Study of Using Self-Experimentation to Detect Individualized Food Triggers

Diagnostic self-tracking, the recording of personal information to diagnose or manage a health condition, is a common practice, especially for people with chronic conditions. Unfortunately, many who attempt diagnostic self tracking have trouble accomplishing their goals. People often lack knowledge and skills needed to design and conduct scientifically rigorous experiments, and current tools provide little support. To address these shortcomings and explore opportunities for diagnostic self tracking, we designed, developed, and evaluated a mobile app that applies a self experimentation framework to support patients suffering from irritable bowel syndrome (IBS) in identifying their personal food triggers. TummyTrials aids a person in designing, executing, and analyzing self experiments to evaluate whether a specific food triggers their symptoms. We examined the feasibility of this approach in a field study with 15 IBS patients, finding that participants could use the tool to reliably undergo a self-experiment. However, we also discovered an underlying tension between scientific validity and the lived experience of self experimentation. We discuss challenges of applying clinical research methods in everyday life, motivating a need for the design of self experimentation systems to balance rigor with the uncertainties of everyday life.

Feasibility and Usability Pilot Study of a Novel Irritable Bowel Syndrome Food and Gastrointestinal Symptom Journal Smartphone App.

OBJECTIVES:Seventy percent of patients with irritable bowel syndrome (IBS) identify certain foods as triggers for their symptom flare-ups. To help identify potential trigger foods, practitioners often rely on patient food and gastrointestinal (GI) symptom journaling. The aim of the study was to evaluate the feasibility and usability of a novel food and symptom journal app, specifically designed for patients with IBS. Secondary aims were to explore the effect of using the app on GI symptoms and to describe associations between diet and GI symptoms suggested by individual patient data.METHODS:The feasibility and usability of the novel app was studied in 11 IBS patients (8 women), aged 21–65 years. Participants were asked to log GI symptoms (abdominal pain, bloating, diarrhea, constipation) using a 100-point color-graded sliding scale (green=none, red=severe) four times a day and to log every meal/snack they ate (at least three times a day) over a 2-week period. The app’s feasibility as a data collection tool was evaluated by daily completion, compliance, data hoarding, and fatigability rates. Usability was evaluated with the System Usability Scale (SUS). To explore potential impact of using the app on bowel distress, we compared before and after intervention IBS-Symptom Severity Scale (IBS-SSS) scores. Meal entries were analyzed for nutrients using the Nutrition Data System for Research. Regression analyses were conducted for each participant journal to explore relationships between meal nutrients and subsequent GI symptoms.RESULTS:Daily average completion rates of the minimum requested entries for meal and GI symptoms were 112±47% and 78±44%, respectively. Average 24-h compliance rates were 90±19% and 94±12%, respectively. The SUS score was above average (mean 83, range 65–97.5; n=10). Most participants did not have a clinically significant decrease in IBS-SSS. At least one strong association (P≤0.05) between GI symptoms and a meal nutrient was found in 73% of participants. The mean number of associations was 2 (range 0–7; n=11). Patterns of associations differed between individual participants.CONCLUSIONS:Our app appeared to be a feasible and usable tool for IBS patients. Our findings are in line with anecdotes that most IBS patients have food triggers and that these vary by individual. Future studies can explore whether individualized dietary changes guided by an app can result in IBS symptom improvement.

A Comprehensive Self-Management Irritable Bowel Syndrome Program Produces Sustainable Changes in Behavior After 1 Year

BACKGROUND & AIMS We developed a comprehensive self-management (CSM) program that combines cognitive behavioral therapy with relaxation and dietary strategies; 9 sessions (1 hour each) over 13 weeks were shown to reduce gastrointestinal symptoms and increase quality of life in a randomized trial of patients with irritable bowel syndrome (IBS), compared with usual care. The aims of this study were to describe strategies patients with IBS selected and continued to use, 12 months after the CSM program began. METHODS We performed a cohort study to continue to follow 81 adults with IBS (87% female; mean age, 45 ± 15 years old) who received the CSM program in the previous clinical trial. During the last CSM session, participants selected strategies they intended to continue using to manage their IBS. CSM strategies were categorized into subthemes of diet (composition, trigger foods, meal size or timing, and eating behaviors), relaxation (specific relaxation strategies and lifestyle behaviors), and alternative thoughts (identifying thought distortions, challenging underlying beliefs, and other strategies). Twelve months later, participants were asked how often they used each strategy (not at all or rarely, occasionally, often, very often, or almost always). RESULTS At the last CSM session, 95% of the patients selected the subthemes of specific relaxation strategies, 90% selected diet composition, and 90% identified thought distortions for continued use. At 12 months, 94% of the participants (76 of 81) were still using at least 6 strategies, and adherence was greater than 79% for all subthemes. CONCLUSIONS We developed a CSM program to reduce symptoms and increase quality of life in patients with IBS that produced sustainable behavioral changes in almost all patients (94%) after 1 year of follow-up.

Opportunities and challenges for self-experimentation in self-tracking

Personal informatics applications support capture and access of data related to an increasing variety of dimensions of everyday life. However, such applications often fail to effectively support diagnostic self-tracking, wherein people seek to answer a specific question about themselves. Current approaches are therefore difficult, tedious, and error-prone. This workshop paper discusses our ongoing efforts to develop methods for self-experimentation in self-tracking. We examine how self-experimentation situates within existing models of personal informatics processes, discuss our current focus on personal food triggers in patients suffering from Irritable Bowel Syndrome, and highlight open challenges for self-experimentation more broadly.