Digital health program improves quality of life in rheumatoid arthritis: a retrospective analysis of real-world data.

OBJECTIVES: Sidekick Health launched a 16-week digital support programme for people with rheumatoid arthritis in 2021. The objective of this retrospective analysis was to understand whether quality of life (QoL; sleep quality, energy and stress levels) improved for users engaged with the programme in a real-world setting. METHODS: This analysis included 635 users who engaged with the programme after the first week, out of 1541 who enrolled. Users self-reported QoL up to four times per week on their phones. Survival bias was investigated by comparing pre-post QoL scores of the full analysis set (all users) and the complete case set (programme completers). Users were divided into highly-engaged and less-engaged groups based on the weekly average number of in-app activities by iterative K-means clustering. Mixed models for repeated measures were used to estimate changes in QoL for highly-versus less-engaged groups. RESULTS: Both the full analysis set and the complete case set had significant pre-post improvements in energy and stress; this suggested that survival bias did not have a substantial effect on these real-world data. Both the highly- and less-engaged groups experienced significant longitudinal improvements in all QoL outcomes. Highly-engaged users achieved better scores in energy, stress, and sleep than less-engaged users. Moreover, a significant time-group interaction for sleep showed that highly-engaged users not only had better sleep scores, but also experienced larger improvements over time than less-engaged users. CONCLUSIONS: These findings demonstrate that a 16-week digital support programme improves self-reported QoL measures, supporting the 2021 EULAR recommendations to incorporate digital healthcare into routine practice. Noteworthy is the study's relevance in the context of the increasing importance of patient empowerment in managing chronic diseases.

User Engagement, Acceptability, and Clinical Markers in a Digital Health Program for Nonalcoholic Fatty Liver Disease: Prospective, Single-Arm Feasibility Study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in the world. Common comorbidities are central obesity, type 2 diabetes mellitus, dyslipidemia, and metabolic syndrome. Cardiovascular disease is the most common cause of death among people with NAFLD, and lifestyle changes can improve health outcomes. OBJECTIVE: This study aims to explore the acceptability of a digital health program in terms of engagement, retention, and user satisfaction in addition to exploring changes in clinical outcomes, such as weight, cardiometabolic risk factors, and health-related quality of life. METHODS: We conducted a prospective, open-label, single-arm, 12-week study including 38 individuals with either a BMI >30, metabolic syndrome, or type 2 diabetes mellitus and NAFLD screened by FibroScan. An NAFLD-specific digital health program focused on disease education, lowering carbohydrates in the diet, food logging, increasing activity level, reducing stress, and healthy lifestyle coaching was offered to participants. The coach provided weekly feedback on food logs and other in-app activities and opportunities for participants to ask questions. The coaching was active throughout the 12-week intervention period. The primary outcome was feasibility and acceptability of the 12-week program, assessed through patient engagement, retention, and satisfaction with the program. Secondary outcomes included changes in weight, liver fat, body composition, and other cardiometabolic clinical parameters at baseline and 12 weeks. RESULTS: In total, 38 individuals were included in the study (median age 59.5, IQR 46.3-68.8 years; n=23, 61% female). Overall, 34 (89%) participants completed the program and 29 (76%) were active during the 12-week program period. The median satisfaction score was 6.3 (IQR 5.8-6.7) of 7. Mean weight loss was 3.5 (SD 3.7) kg (P<.001) or 3.2% (SD 3.4%), with a 2.2 (SD 2.7) kg reduction in fat mass (P<.001). Relative liver fat reduction was 19.4% (SD 23.9%). Systolic blood pressure was reduced by 6.0 (SD 13.5) mmHg (P=.009). The median reduction was 0.14 (IQR 0-0.47) mmol/L for triglyceride levels (P=.003), 3.2 (IQR 0.0-5.4) µU/ml for serum insulin (s-insulin) levels (P=.003), and 0.5 (IQR -0.7 to 3.8) mmol/mol for hemoglobin A1c (HbA1c) levels (P=.03). Participants who were highly engaged (ie, who used the app at least 5 days per week) had greater weight loss and liver fat reduction. CONCLUSIONS: The 12-week-long digital health program was feasible for individuals with NAFLD, receiving high user engagement, retention, and satisfaction. Improved liver-specific and cardiometabolic health was observed, and more engaged participants showed greater improvements. This digital health program could provide a new tool to improve health outcomes in people with NAFLD. TRIAL REGISTRATION: Clinicaltrials.gov NCT05426382; https://clinicaltrials.gov/study/NCT05426382.

A New Digital Health Program for Patients With Inflammatory Bowel Disease: Preliminary Program Evaluation.

BACKGROUND: Inflammatory bowel disease (IBD) causes chronic inflammation of the gastrointestinal tract. IBD is characterized by an unpredictable disease course that varies greatly between individuals and alternates between the periods of relapse and remission. A low energy level (fatigue) is a common symptom, whereas stress and reduced sleep quality may be the triggering factors. Therapeutic guidelines call for effective disease assessment, early intervention, and personalized care using a treat-to-target approach, which may be difficult to achieve through typical time- and resource-constrained standard care. Providing patients with a digital health program that incorporates helpful self-management features and patient support to complement standard care may be optimal for improving the disease course. OBJECTIVE: This study aimed to perform a preliminary program evaluation, analyzing engagement and preliminary effectiveness and the effect on participants' energy levels (fatigue), stress, and sleep quality, of a newly developed 16-week digital health program (SK-311 and SK-321) for patients with IBD. METHODS: Adults with IBD were recruited to participate in a real-world, live, digital health program via Finnish IBD patient association websites and social media. No inclusion or exclusion criteria were applied for this study. Baseline characteristics were entered by the participants upon sign-up. Platform engagement was measured by tracking the participants' event logs. The outcome measures of stress, energy levels (fatigue), and quality of sleep were reported by participants through the platform. RESULTS: Of the 444 adults who registered for the digital health program, 205 (46.2%) were included in the intention-to-treat sample. The intention-to-treat participants logged events on average 41 times per week (5.9 times per day) during the weeks in which they were active on the digital platform. More women than men participated in the intervention (126/205, 88.7%). The mean age of the participants was 40.3 (SD 11.5) years, and their mean BMI was 27.9 (SD 6.0) kg/m2. In total, 80 people provided the required outcome measures during weeks 12 to 16 (completers). Treatment completion was strongly predicted by the number of active days in week 1. Analysis of the completers (80/205, 39%) showed significant improvements for stress (t79=4.57; P<.001; percentage change=-23.26%) and energy levels (t79=-2.44; P=.017; percentage change=9.48%); however, no significant improvements were observed for quality of sleep (t79=-1.32; P=.19). CONCLUSIONS: These results support the feasibility of a digital health program for patients with IBD (SK-311 and SK-321) and suggest that treatment completion might have a substantial positive effect on patient-reported stress and energy levels in a real-world setting. These findings are promising and provide initial support for using the Sidekick Health digital health program to supplement standard care for patients with IBD.

Engagement, Retention, and Acceptability in a Digital Health Program for Atopic Dermatitis: Prospective Interventional Study.

BACKGROUND: Patients with atopic dermatitis can experience chronic eczema with pruritus, skin pain, sleep problems, anxiety, and other problems that reduce their quality of life (QoL). Current treatments aim to improve these symptoms and reduce inflammation, but poor treatment adherence and disease understanding are key concerns in the long-term management of atopic dermatitis. Digital therapeutics can help with these and support patients toward a healthier lifestyle to improve their overall QoL. OBJECTIVE: The aim of the study is to test the feasibility of a digital health program tailored for atopic dermatitis through program engagement, retention, and acceptability. METHODS: Adults with atopic dermatitis were recruited in Iceland for a 6-week digital health program delivered through a smartphone app. Key components of the digital program were disease and trigger education; medication reminders; patient-reported outcomes (PROs) on energy levels, stress levels, and quality of sleep (referred to as QoL PROs); atopic dermatitis symptom PROs; guided meditation; and healthy lifestyle coaching. The primary outcome was program feasibility, as assessed by in-app retention and engagement. User satisfaction was assessed by the mHealth (ie, mobile health) App Usability Questionnaire (MAUQ). RESULTS: A total of 21 patients were recruited (17 female, mean age 31 years), 20 (95%) completed the program. On average, users were active in the app 6.5 days per week and completed 8.2 missions per day. The education content, medication reminders, and PROs had high user engagement and retention; all users who were exposed to the QoL PROs (n=17) interacted with these, and 20/21 (95%) users were continuously engaged with the education missions, medication missions, and symptom PROs. Continued engagement with the step counter and mind missions among exposed users was lower (17/21 and 13/20 participants, respectively). Medication reminder and education task completion remained high over time (at least 18/20, 90%), but weekly interactions declined. All assigned users completed atopic dermatitis symptom PROs on weeks 1-5 and only one did not do so on week 6; the reported number and total severity of atopic dermatitis symptoms reduced during the program. Regarding the QoL PROs, 16/17 (94%) and 14/17 (82%) users interacted with these at least 3 times in the first and last week of the program, respectively, and all reported improvements over time. User satisfaction was high with a total score of 6.2/7. CONCLUSIONS: We found high overall engagement and retention in a targeted digital health program among patients with atopic dermatitis, as well as high compliance with missions relating to medication reminders, patient education, and PROs. Symptom number and severity were reduced, and QoL PROs improved over time. We conclude that a digital health program is feasible and may provide added benefits for patients with atopic dermatitis, including the tracking and improvement of atopic dermatitis symptoms.

Improving outpatient care for heart failure through digital innovation: a feasibility study.

BACKGROUND: Heart failure (HF) affects over 26 million people worldwide. Multidisciplinary management strategies that include symptom monitoring and patient self-care support reduce HF hospitalization and mortality rates. Ideally, HF follow-up and self-care support includes lifestyle-change recommendations and remote monitoring of weight and HF symptoms. Providing these via a digital solution may be ideal for improving HF disease outcomes and reducing the burden on providers and healthcare systems. This study's main objective was to assess the feasibility of a digital solution including remote monitoring, lifestyle-change, and self-care support for HF outpatients in Iceland. METHODS: Twenty HF patients (mean age 57.5 years, 80% males) participated in an 8-week study. They were provided with a digital solution (SK-141), including lifestyle-change and disease self-care support, a remote symptom monitoring system, and a secure messaging platform between healthcare providers and patients. This feasibility study aimed to assess patient acceptability of this new intervention, retention rate, and to evaluate trends in clinical outcomes. To assess the acceptability of SK-141, participants completed a questionnaire about their experience after the 8-week study. Participants performed daily assigned activities (missions), including self-reporting symptoms. Clinical outcomes were assessed with the Hospital Anxiety and Depression Scale and the Kansas City Cardiomyopathy Questionnaire at the study's beginning and end with an online survey. RESULTS: Of the 24 patients invited, 20 were elected to participate. The retention rate of participants throughout the 8-week period was high (80%). At the end of the 8 weeks, thirteen participants completed a questionnaire about their experience and acceptability of the SK-141. They rated their experience positively including on questions whether they would recommend the solution to others (6.8 on a scale of 1-7), whether the solution had improved their life and well-being (5.7 on a scale of 1-7), and whether it was user friendly (5.5 on a scale of 1-7). Many of the clinical parameters studied exhibited a promising trend towards improvement over the 8-week period. CONCLUSION: The digital solution, SK-141, was very acceptable to patients and also showed promising clinical results in this small feasibility study. These results encourage us to conduct a longer, more extensive, adequately powered, randomized-controlled study to assess whether this digital solution can improve the quality of life and clinical outcomes among HF patients.

Clinical Efficacy of a Digital Intervention for Patients with Atopic Dermatitis: a Prospective Single-Center Study.

INTRODUCTION: Improving disease awareness and treatment adherence is key for the long-term management of atopic dermatitis (AD). Digital interventions can support patients in disease self-management and adopting a healthier lifestyle through behavioral modifications. We aimed to test the clinical efficacy of a digital program in patients with AD. METHODS: Adults with mild-to-severe AD were recruited for a 6-week feasibility study. The intervention was delivered through a mobile app and consisted of symptom and trigger education, treatment reminders, lifestyle coaching, and healthy lifestyle support. Here we report the secondary outcomes of intervention efficacy on clinical symptoms, as assessed by Scoring Atopic Dermatitis (SCORAD) and Patient-Oriented Eczema Measure (POEM), on health-related quality of life (HR QoL) as assessed by Dermatology Life Quality Index (DLQI), and changes in behaviors related to disease management as assessed by a six-item questionnaire. RESULTS: Twenty of 21 patients (95.2%) completed the program (81% female, mean age 31.4 years, mean time from diagnosis 26.8 years). Clinical symptoms and patient-reported global severity improved by 44% and 46%, respectively, while HR QoL improved by 41% (p < 0.001 for all measures). Adherence to treatments and preventive measures improved from pre- to post-intervention, including skincare, avoidance of triggers, and disease-related knowledge. A significant interaction was observed between increased treatment adherence and clinical improvement, such that larger clinical improvements were observed in patients with higher treatment adherence. CONCLUSION: Patients with AD are open to and can benefit from a digitally delivered targeted intervention, as demonstrated by significant improvements in treatment adherence and related clinical outcomes.

Evaluating the Feasibility of a Digital Therapeutic Program for Patients With Cancer During Active Treatment: Pre-Post Interventional Study.

BACKGROUND: Increasing evidence shows that lifestyle interventions can improve the symptoms, quality of life (QoL), and even overall survival of patients with cancer. Digital therapeutics (DTx) can help implement behavioral modifications and empower patients through education, lifestyle support, and remote symptom monitoring. OBJECTIVE: We aimed to test the feasibility of a DTx program for patients with cancer, as measured by engagement, retention, and acceptability. In addition, we explored the effects of the program on cancer-related QoL. METHODS: We conducted a 4-week single-arm trial in Iceland, where DTx was delivered through a smartphone app. The intervention consisted of patient education about mindfulness, sleep, stress, and nutrition; lifestyle coaching; and the completion of daily missions for tracking physical activity and exercise, reporting patient-reported outcomes (PROs), practicing mindfulness, and logging healthy food intake. Information on program engagement and retention, step goal attainment, as well as PROs were collected throughout the study. QoL was measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 at baseline and follow-up. RESULTS: In total, 30 patients with cancer undergoing active therapy were enrolled, and 29 registered in the app (23 female, 18 with breast cancer; mean age 52.6, SD 11.5 years). Overall, 97% (28/29) of participants were active in 3 of the 4 weeks and completed the pre- and postprogram questionnaires. The weekly active days (median) were 6.8 (IQR 5.8-6.8), and 72% (21/29) of participants were active at least 5 days a week. Users interacted with the app on average 7.7 (SD 1.9) times per day. On week 1, all 29 participants used the step counter and logged an average of 20,306 steps; 21 (72%) participants reached their step goals of at least 3000 steps per day. On week 4, of the 28 active users, 27 (96%) were still logging their steps, with 19 (68%) reaching their step goals. Of the 28 participants who completed the satisfaction questionnaire, 25 (89%) were likely to recommend the program, 23 (82%) said the program helped them deal with the disease, and 24 (86%) said it helped them remember their medication. QoL assessment showed that the average global health status, functioning, and symptom burden remained stable from baseline to follow-up. In all, 50% (14/28) of participants reported less pain, and the average pain score decreased from 31 (SD 20.1) to 22.6 (SD 23.2; P=.16). There was no significant change in PROs on the quality of sleep, energy, and stress levels from the first to the last week. CONCLUSIONS: The high retention, engagement, and acceptability found in this study demonstrate that multidisciplinary DTx is feasible for patients with cancer. A longer, full-scale randomized controlled trial is currently being planned to evaluate the efficacy of the intervention.

Randomized Trial for Weight Loss Using a Digital Therapeutic Application.

BACKGROUND: Smartphones present a near-ubiquitous channel through which structured lifestyle change can reduce risk or progression of the most common noncommunicable diseases. We explored whether a digital structured lifestyle program enhances weight loss. METHODS: We randomized overweight and obese participants attending a four-month lifestyle change program to either standard weekly coaching sessions (controls), or standard treatment supplemented with a digital therapeutic mobile application (intervention). Changes in body mass index after four months were the main outcome measure. Odds ratios of achieving 5% weight loss were estimated with unconditional logistic regression. RESULTS: Of 234 eligible persons, 146 (62%) agreed to participate, were block-randomized, showed up for the baseline measures, and constituted the intention-to-treat (ITT) sample (n = 95 intervention group, n = 51 control group). In the intervention group, 70 (74%) downloaded the mobile application and completed the program (intervention per-protocol). Significant weight loss and BMI reduction were observed for both the intention-to-treat intervention group (P < 0.05, P = 0.01) and the per-protocol intervention group (P < 0.0001, P < 0.0001). For the intervention per-protocol group, the odds ratio of achieving 5% weight loss, compared to not treated per-protocol, was 3.3 (95% CI 1.3-8.2), adjusting for age and weight at baseline.Attendance to weekly coaching sessions decreased by 18% during the program in the control group while it increased by 3% amongst the per-protocol group (P = 0.004). CONCLUSIONS: These preliminary findings support the benefit of a digital therapeutic to enhance weight reduction and attendance in a structured lifestyle change program. Larger trials of longer duration are needed to confirm these findings.

[Outcome of myocardial revascularisation in Iceland]. / Árangur kransaedahjáveituadgerda á Íslandi 2002-2006.

INTRODUCTION: In Iceland over 3500 coronary artery bypass operations have been performed, both On-Pump, using cardiopulmonary bypass and Off-Pump, surgery on a beating heart. The aim was to study their outcome. MATERIAL AND METHODS: This was a retrospective study on 720 consecutive patients who underwent surgical revascularisation at Landspítali-The National University Hospital of Iceland between 2002-2006; 513 On-Pump and 207 Off-Pump patients. Complications and operative mortality (<30 days) were compared between the groups and predictors of survival identified using multivariate analysis. RESULTS: The number of males was significantly higher in the On-Pump group, but other risk factors of coronary artery disease, including age and high body mass index, were comparable, as were the number of distal anastomoses and EuroSCORE. The Off-Pump procedure took 25 minutes longer on average and chest tube output was significantly increased, but the amount of transfusions administered was similar. The rate of minor complications was higher in the On-Pump group. Of the major complications, stroke rates were similar in both groups (2%) but the rate of reoperation for bleeding was higher in the On-Pump group. Mean length of hospital stay was one day longer for On-Pump patients but operative mortality was similar for both groups (4% vs. 3%, p=0.68) as was 5 year survival (92% in both groups). In multivariate analysis both EuroSCORE and age predicted outcome of operative mortality and long term survival but type of surgery (On-Pump vs. Off-Pump) was not a predictive variant. CONCLUSIONS: Outcome of myocardial revascularisation in Iceland is good as regards operative mortality and long term survival. This applies to both conventional On-Pump and Off-Pump procedures.

Lower mortality following coronary arterial revascularization in patients taking statins.

OBJECTIVES: Numerous studies have suggested that statins have beneficial non-lipid-lowering effects, including reduction of systemic inflammatory response following surgery. We wanted to evaluate the effect of preoperative statin treatment on complications and operative mortality after coronary arterial revascularization. DESIGN: We performed a retrospective study of 720 consecutive patients who underwent on-pump coronary artery bypass grafting (CABG) (n = 513) or off-pump (OPCAB) (n = 207) in Iceland from 2002-2006. Patients taking statins preoperatively (n = 529) were compared with those not taking statins (n = 191). Predictors of complications and operative mortality were evaluated by univariate and multivariate analysis. RESULTS: Cardiovascular risk profiles were similar. However, hypertension was more common in the statin group but EuroSCORE was slightly lower. Operative mortality was significantly lower in patients taking statins (1.7% vs. 5.8%, p < 0.001). There were no significant differences in the incidence of major complications. Multivariate analysis showed that preoperative statin treatment was an independent predictor of lower operative mortality (OR = 0.33, p = 0.043), even after adjusting for EuroSCORE, acute operations, advanced age, or other medications. CONCLUSIONS: In this non- randomized study, patients taking statins had lower operative mortality than the controls after adjusting for multiple confounders. The reason for this might be linked to pleiotropic effects of statins.

[Impact of obesity on surgical outcomes following coronary artery bypass graft surgery]. / Tengsl offitu við árangur kransæðahjáveituaðgerða.

INTRODUCTION: Obesity has been related to increased postoperative morbidity and mortality following open-heart surgery. However, recent studies have shown no association or even a more favourable outcome in obese patients. This relationship was investigated in a well-defined cohort of patients that underwent myocardial revascularisation in Iceland. MATERIAL AND METHODS: A retrospective study including all patients that underwent isolated myocardial revascularisation in Iceland from 2002 to 2006. Altogether 720 patients were divided into two groups, an obese group, with BMI >30 kg/m2 (n=207, 29%), and a non-obese group with BMI ≤30 kg/m2 (n=513, 71%). Patient demographics, complications, operative mortality and long term survival of both groups were compared. RESULTS: Demographics were comparable between the groups. Obese patients were 2.4 years younger, more likely to use statins (83,3% vs. 71,2%, had a significantly lower EuroSCORE (4.3 vs. 5.0) but a slightly longer operation time. Pleural fluid was less often drained in obese patients (8.2 vs. 15.0%) but rates for other complications were similar in both groups, as was operative mortality ≤30 days (2.0% vs. 3.7%), 1 and 5 year survival. In a multivariate analysis obesity was not an independent risk factor for minor or major complications, operative mortality or long term survival. CONCLUSION: The rate of complications and operative mortality after myocardial revascularisation is not significantly higher in obese patients and the same applies to long term survival. This is true even after correcting for confounding factors in a multivariate analysis.

[Pulmonary sequestration in Iceland - two case reports]. / Adskilinn lungnahluti (pulmonary sequestration) med tengsl vid meltingarveg. Tvö sjúkratilfelli sem rökstydja ad um medfaeddan galla sé ad raeda.

Pulmonary sequestration (PS) is a rare disease where non-functioning lung tissue is separated from the normal bronchopulmonary tree and vasularized by an aberrant systemic artery. The origin of PS is not fully understood. Here we describe two unique cases of PS that support the hypothesis that PS is a congenital malformation rather than an acquired one. These are also the first Icelandic cases of PS reported.

Bilateral extralobar pulmonary sequestration communicating with the upper gastrointestinal system in a newborn with duodenal atresia.

We report a rare form of bilateral pulmonary sequestration (PS) that was directly connected to the gastroesophageal junction with a well-formed aberrant bronchus-like structure. An upper gastrointestinal contrast series was performed directly after birth, and a unique PS bronchogram was identified, along with duodenal atresia. The PS was successfully resected and the duodenal atresia was corrected.

[Desmoid tumor of chest wall--an important differential diagnosis to malignancies]. / Desmoid-aexli í brjóstvegg--mikilvaeg mismunagreining vieth illkynja mein.

Desmoid tumors are rare solid tumors that arise from musculoaponeurotic tissues. They are classified as benign as they do not metastasize. Desmoid tumors can, however, exhibit rapid local growth and clinically they can mimic sarcomas. Their histological appearance can also resemble some malignant neoplasms such as low grade sarcomas, rendering the differential diagnosis difficult. The present report describes a 60-year-old woman with a history of left mastectomy, performed for a lymph node negative adenocarcinoma. At follow-up 4 years later, a solid nodule was palpated below the right breast. The tumor increased in size over several weeks and caused local radiating chest pain. Clinically a breast cancer metastasis was suspected. Open biopsy revealed a desmoid tumor. The tumor was resected together with a part of the anterior hemithorax, and the defect in the chest wall covered with a Goretex-patch. Six months postoperatively, the patient is doing well with no signs of locally recurrent disease.

TGF-beta type II receptor-deficient thymocytes develop normally but demonstrate increased CD8+ proliferation in vivo.

We have taken advantage of the Cre/lox system to generate a mouse model with inducible deficiency of transforming growth factor beta receptor II (TbetaRII). Using this approach, transforming growth factor beta (TGF-beta) signaling deficiency can be restricted to the hematopoietic system by bone marrow transplantation. Mice that received transplants with TbetaRII-/- bone marrow develop a lethal inflammatory disorder closely resembling that of TGF-beta1-null mice. Previous in vitro studies have suggested multiple roles for TGF-beta in T-cell development, including proliferation, apoptosis, and differentiation. We used our transplantation model to ask whether T-cell development is normal in the absence of TGF-beta signaling. The findings show for the first time in vivo and in fetal thymus organ culture (FTOC) that TGF-beta is not required for thymocytes to differentiate along the entire pathway of thymic T-cell development, as defined by the expression patterns of CD4, CD8, CD25, and CD44. In contrast to previous investigations, no increase of thymocyte apoptosis was observed. However, TbetaRII-deficient CD8+ thymocytes displayed a 2-fold increase in proliferation rate, as determined by bromodeoxyuridine (BrdU) incorporation in vivo. These results reinforce the importance of TGF-beta as an immune regulator critical for T-cell function.