Sherif M. Badawy

Subtle differences in CTL cytotoxicity determine susceptibility to hemophagocytic lymphohistiocytosis in mice and humans with Chediak-Higashi syndrome.

Perforin-mediated cytotoxicity is important for controlling viral infections, but also for limiting immune reactions. Failure of this cytotoxic pathway leads to hemophagocytic lymphohistiocytosis (HLH), a life-threatening disorder of uncontrolled T-cell and macrophage activation. We studied susceptibility to HLH in 2 mouse strains (souris and beige(J)) and a cohort of patients with partial defects in perforin secretion resulting from different mutations in the LYST gene. Although both strains lacked NK-cell cytotoxicity, only souris mice developed all clinical and histopathologic signs of HLH after infection with lymphocytic choriomeningitis virus. The 2 strains showed subtle differences in CTL cytotoxicity in vitro that had a large impact on virus control in vivo. Whereas beige(J) CTLs eliminated lymphocytic choriomeningitis virus infection, souris CTLs failed to control the virus, which was associated with the development of HLH. In LYST-mutant patients with Chediak-Higashi syndrome, CTL cytotoxicity was reduced in patients with early-onset HLH, whereas it was retained in patients who later or never developed HLH. Thus, the risk of HLH development is set by a threshold that is determined by subtle differences in CTL cytotoxicity. Differences in the cytotoxic capacity of CTLs may be predictive for the risk of Chediak-Higashi syndrome patients to develop HLH.

Technology Access and Smartphone App Preferences for Medication Adherence in Adolescents and Young Adults With Sickle Cell Disease

Hydroxyurea is the only Food and Drug Administration approved medication for sickle cell disease (SCD) with short‐ and long‐term benefits for both morbidity and mortality. However, hydroxyurea underutilization and adherence remain challenges for patients with SCD. The objectives of this study were to determine access to technology among adolescents and young adults (AYA) with SCD and to identify their preferred technology‐based strategies for improving medication adherence.

Text Messaging and Mobile Phone Apps as Interventions to Improve Adherence in Adolescents With Chronic Health Conditions: A Systematic Review

Background The number of adolescents with chronic health conditions (CHCs) continues to increase. Medication nonadherence is a global challenge among adolescents across chronic conditions and is associated with poor health outcomes. While there has been growing interest in the use of mHealth technology to improve medication adherence among adolescents with CHCs, particularly text messaging and mobile phone apps, there has been no prior systematic review of their efficacy. Objective The purpose of this review was to systematically evaluate the most recent evidence for the efficacy of text messaging and mobile phone apps as interventions to promote medication adherence among adolescents with CHCs. Methods PubMed, Embase, CENTRAL, PsycINFO, Web of Science, Google Scholar, and additional databases were searched from 1995 until November 2015. An additional hand search of related themes in the Journal of Medical Internet Research was also conducted. The Preferred Reporting Results of Systematic Reviews and Meta-Analyses guidelines were followed. Two reviewers independently screened titles/abstracts, assessed full-text articles, extracted data from included articles, and assessed their quality using Grades of Recommendation, Assessment, Development, and Evaluation criteria. Included studies were described in original research articles that targeted adherence in adolescents with CHCs (12-24 years-old). Results Of the 1423 records examined, 15 met predefined criteria: text messaging (n=12) and mobile phone apps (n=3). Most studies were performed in the United States (11/15, 73%), were randomized-controlled trials (8/15, 53%), had a sample size <50 (11/15, 73%), and included adherence self-report and/or biomarkers (9/15, 60%). Only four studies were designed based on a theoretical framework. Approaches for text messaging and mobile phone app interventions varied across studies. Seven articles (7/15, 47%) reported significant improvement in adherence with moderate to large standardized mean differences. Most of the included studies were of low or moderate quality. Studies varied in sample size, methods of adherence assessment, and definition of adherence, which prohibited performing a meta-analysis. Conclusions The use of text messaging and mobile phone app interventions to improve medication adherence among adolescents with CHCs has shown promising feasibility and acceptability, and there is modest evidence to support the efficacy of these interventions. Further evaluation of short- and long-term efficacy and cost-effectiveness of these interventions is warranted given the early and evolving state of the science.

Texting and Mobile Phone App Interventions for Improving Adherence to Preventive Behavior in Adolescents: A Systematic Review

Background Many preventable behaviors contribute to adolescent mortality and morbidity. Non-adherence to preventive measures represents a challenge and has been associated with worse health outcomes in this population. The widespread use of electronic communication technologies by adolescents, particularly the use of text messaging (short message service, SMS) and mobile phones, presents new opportunities to intervene on risk and preventive risk behavior, but little is known about their efficacy. Objective This study aimed to systematically evaluate evidence for the efficacy of text messaging and mobile phone app interventions to improve adherence to preventive behavior among adolescents and describe intervention approaches to inform intervention development. Methods This review covers literature published between 1995 and 2015. Searches included PubMed, Embase, CENTRAL, PsycINFO, CINAHL, INSPEC, Web of Science, Google Scholar, and additional databases. The search strategy sought articles on text messaging and mobile phone apps combined with adherence or compliance, and adolescents and youth. An additional hand search of related themes in the Journal of Medical Internet Research was also conducted. Two reviewers independently screened titles and abstracts, assessed full-text articles, and extracted data from articles that met inclusion criteria. Included studies reflect original research—experimental or preexperimental designs with text messaging or mobile phone app interventions—targeting adherence to preventive behavior among adolescents (12-24 years old). The preferred reporting items of systematic reviews and meta-analyses (PRISMA) guidelines were followed for reporting results, and findings were critically appraised against the Oxford Centre for Evidence-based Medicine criteria. Results Of 1454 records, 19 met inclusion criteria, including text messaging (n=15) and mobile phone apps (n=4). Studies targeted clinic attendance, contraceptive use, oral health, physical activity and weight management, sun protection, human papillomavirus (HPV) vaccination, smoking cessation, and sexual health. Most studies were performed in the United States (47%, 9/19), included younger adolescents (63%, 12/19), and had sample size <100 (63%, 12/19). Although most studies were randomized controlled trials (RCTs; 58%, 11/19), only 5 followed an intent-to-treat analysis. Only 6 of 19 studies (32%) incorporated a theoretical framework in their design. Most studies reported good feasibility with high acceptability and satisfaction. About half of the included studies (42%, 8/19) demonstrated significant improvement in preventive behavior with moderate standardized mean differences. As early efforts in this field to establish feasibility and initial efficacy, most studies were low to moderate in quality. Studies varied in sample size and methods of preventive behavior adherence or outcome assessment, which prohibited performing a meta-analysis. Conclusions Despite the promising feasibility and acceptability of text messaging and mobile phone apps in improving preventive behavior among adolescents, overall findings were modest in terms of efficacy. Further research evaluating the efficacy, effectiveness, and cost-effectiveness of these intervention approaches in promoting preventive behavior among adolescents is needed.

Economic Evaluation of Text-Messaging and Smartphone-Based Interventions to Improve Medication Adherence in Adolescents with Chronic Health Conditions: A Systematic Review

Background The rate of chronic health conditions (CHCs) in children and adolescents has doubled in the past 20 years, with increased health care costs. Technology-based interventions have demonstrated efficacy to improving medication adherence. However, data to support the cost effectiveness of these interventions are lacking. Objective The objective of this study is to conduct an economic evaluation of text-messaging and smartphone-based interventions that focus on improving medication adherence in adolescents with CHCs. Methods Searches included PubMed MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, Web of Science, and Inspec. Eligibility criteria included age (12-24 years old), original articles, outcomes for medication adherence, and economic outcomes. Results Our search identified 1118 unique articles that were independently screened. A total of 156 articles met inclusion criteria and were then examined independently with full-text review. A total of 15 articles met most criteria but lacked economic outcomes such as cost effectiveness or cost-utility data. No articles met all predefined criteria to be included for final review. Only 4 articles (text messaging [n=3], electronic directly observed therapy [n=1]) described interventions with possible future cost-saving but no formal economic evaluation. Conclusions The evidence to support the cost effectiveness of text-messaging and smartphone-based interventions in improving medication adherence in adolescents with CHCs is insufficient. This lack of research highlights the need for comprehensive economic evaluation of such interventions to better understand their role in cost-savings while improving medication adherence and health outcomes. Economic evaluation of technology-based interventions can contribute to more evidence-based assessment of the scalability, sustainability, and benefits of broader investment of such technology tools in adolescents with CHCs.

Health-related quality of life and adherence to hydroxyurea in adolescents and young adults with sickle cell disease

Complications related to sickle cell disease (SCD) result in significant declines in health‐related quality of life (HRQOL). While hydroxyurea reduces SCD complications, adherence remains suboptimal. The studys objectives were to assess the feasibility of Internet‐based electronic assessment of HRQOL in SCD clinic and to examine the relationship between HRQOL and hydroxyurea adherence in adolescents and young adults (AYAs) with SCD.

Barriers to hydroxyurea adherence and health-related quality of life in adolescents and young adults with sickle cell disease

To identify barriers to hydroxyurea adherence (negative beliefs, access, and/or recall barriers), and their relationship to adherence rates and health‐related quality of life (HRQOL) among adolescents and young adults (AYA) with sickle cell disease (SCD).

Assessment of musculoskeletal function and mood in haemophilia A adolescents: a cross‐sectional study

Summary.  Haemophilia A is characterized by the occurrence of frequent spontaneous intra‐articular and intramuscular bleeding. If inadequately treated, it results in progressive damage to joints and muscles leading to crippling deformities and musculoskeletal dysfunction. These complications result in lifelong chronic pain and disability that may greatly affect the patients’ mood. We aimed to evaluate the musculoskeletal function in our haemophilia A patients and its correlation to depressed mood in these patients and determine the impact of degree of factor VIII deficiency, different replacement therapy regimens and frequency of hemarthrosis, on both musculoskeletal function and mood. A cross‐sectional study was carried out on 50 adolescent haemophilia A patients. Musculoskeletal function was assessed using Functional Independence Score for Hemophilia (FISH) and mood status was assessed using Beck Depression Inventory—Short Form (BDI‐SF). The mean FISH score was 23.32 ± 4.69 (range 13–28) and the tasks that obtained lower scores were step climbing, squatting and walking. Of our 50 patients included, 16(32%) were not depressed, 18(36%) were with mild depression, 11(22%) were with moderate depression and 5(10%) were with severe depression. There was a highly significant negative correlation between mean FISH score and mean BDI‐SF score (P < 0.001). The better the replacement therapy regimen, the better the musculoskeletal function that could be obtained in haemophilia A patients and the better the mood.

Assessing cardiac and liver iron overload in chronically transfused patients with sickle cell disease.

Transfusional iron overload represents a substantial challenge in the management of patients with sickle cell disease (SCD) who receive chronic or episodic red blood cell transfusions. Iron‐induced cardiomyopathy is a leading cause of death in other chronically transfused populations but rarely seen in SCD. Study objectives were to: (i) examine the extent of myocardial and hepatic siderosis using magnetic resonance imaging (MRI) in chronically transfused SCD patients, and (ii) evaluate the relationship between long‐term (over the 5 years prior to enrolment) mean serum ferritin (MSF), spot‐ferritin values and liver iron content (LIC) measured using MRI and liver biopsy. Thirty‐two SCD patients (median age 15 years) with transfusional iron overload were recruited from two U.S. institutions. Long‐term MSF and spot‐ferritin values significantly correlated with LIC by MRI‐R2* (r = 0·77, P < 0·001; r = 0·82, P < 0·001, respectively). LIC by MRI‐R2* had strong positive correlation with LIC by liver biopsy (r = 0·98, P < 0·001) but modest inverse correlation with cardiac MRI‐T2* (r = −0·41, P = 0·02). Moderate to severe transfusional iron overload in SCD was not associated with aberrations in other measures of cardiac function based on echocardiogram or serum biomarkers. Our results suggest that SCD patients receiving chronic transfusions may not demonstrate significant cardiac iron loading irrespective of ferritin trends, LIC and erythropoiesis suppression.

Pediatric and Teen Ovarian Tissue Removed for Cryopreservation Contains Follicles Irrespective of Age, Disease Diagnosis, Treatment History, and Specimen Processing Methods

PURPOSE Fertility preservation in a pediatric and teen female population is challenging because standard technologies of egg and embryo freezing may not be possible due to premenarcheal status. Ovarian tissue cryopreservation (OTC) with the intent of future ovarian tissue transplantation or in vitro follicle growth may be the only option to preserve fertility. The purpose of this study was to add to the general understanding of primordial follicle dynamics in young patients. METHODS First, the unique infrastructure of the Oncofertility Consortium National Physicians Cooperative (OC-NPC) is described, which simultaneously drives clinical fertility preservation and basic research to explore and expand the reproductive options for those in need. Then, the OC-NPC research resource is used to perform a histological evaluation of ovarian tissue from 24 participants younger than 18 years of age. RESULTS Primordial follicles, which comprise the ovarian reserve, were observed in all participant tissues, irrespective of variables, including age, diagnosis, previous treatment history, tissue size, and tissue processing methods. Primordial follicles were present in ovarian tissue, even in participants who had a previous history of exposure to chemotherapy and/or radiation treatment regimens, which placed them at risk for iatrogenic infertility or premature ovarian failure. CONCLUSION Primordial follicles were observed in ovarian tissue from all participants examined, despite population and tissue heterogeneity. These results increase the understanding of human follicle dynamics and support OTC as a promising fertility preservation modality in the young female population. Future studies to evaluate follicle quality within these tissues are warranted.