An evaluation of deferiprone as twice-a-day tablets or in combination therapy for the treatment of transfusional iron overload in thalassemia syndromes.

INTRODUCTION: Regular blood transfusions in patients with thalassemia syndromes can cause iron overload resulting in complications including cirrhosis, heart problems, or endocrine abnormalities. To prevent iron overload toxicity in these patients, three iron chelators are currently FDA-approved for use: deferoxamine, deferasirox, and deferiprone. In the United States, deferiprone has been approved for three times daily dosing since 2011 and has recently gained approval for twice-daily administration. AREAS COVERED: A PubMed literature search was performed with the keywords 'deferiprone' and 'thalassemia.' Relevant original research studying deferiprone's effects on transfusional iron overload in patients with thalassemia syndromes was included. Exclusion criteria included case reports and review papers. Deferiprone is effective at reducing serum ferritin levels in patients with iron overload. Twice-daily administration provides a similar level of iron chelation as three times daily dosing with a comparable side effect profile and increased patient acceptability. EXPERT OPINION: New studies are highlighting deferiprone's potential for combination therapy with either deferoxamine or deferasirox to improve iron chelation. Deferiprone's ability to significantly decrease cardiac and liver iron content can be utilized in other transfusion-dependent hematologic conditions, as evidenced by its recent approval for use in the United States for sickle cell disease or other anemias.

Telemedicine in Malignant and Nonmalignant Hematology: Systematic Review of Pediatric and Adult Studies.

BACKGROUND: Telemedicine, including video-, web-, and telephone-based interventions, is used in adult and pediatric populations to deliver health care and communicate with patients. In the realm of hematology, telemedicine has recently been used to safely and efficiently monitor treatment side-effects, perform consultations, and broaden the reach of subspecialty care. OBJECTIVE: We aimed to synthesize and analyze information regarding the feasibility, acceptability, and potential benefits of telemedicine interventions in malignant and nonmalignant hematology, as well as assess the recognized limitations of these interventions. METHODS: Studies were identified through a comprehensive Medical Subject Headings (MeSH) search on the PubMed MEDLINE, Controlled Register of Clinical Trials (Cochrane CENTRAL from Wiley), Embase, and CINAHL (EBSCO) databases on February 7, 2018. A second search, utilizing the same search strategy, was performed on October 1, 2020. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in the reporting of included evidence. Included studies were original articles researching the feasibility, acceptability, and clinical outcomes of telemedicine or telehealth interventions in pediatric or adult populations with malignant or nonmalignant hematological conditions. Data items in the extraction form included first author name, publication year, country, malignant or nonmalignant hematological condition or disease focus of the study, participant age, participant age subgroup (pediatric or adult), study design and setting, telemedicine intervention type and description, study purpose, and main study outcomes. RESULTS: A total of 32 articles met the preset criteria and were included in this study. Most (25/32) studies were conducted in adults, and the remaining (7/32) were conducted in the pediatric population. Of the 32 studies, 12 studied malignant hematological conditions, 18 studied nonmalignant conditions, and two studied both malignant and nonmalignant conditions. Study types included pilot study (11/32), retrospective study (9/32), randomized controlled trial (6/32), cross-sectional study (2/32), case study (1/32), pre-post study (1/32), noncomparative prospective study (1/32), and prospective cohort study (1/32). The three main types of telemedicine interventions utilized across all studies were video-based (9/32), telephone-based (9/32), and web-based interventions (14/32). Study results showed comparable outcomes between telemedicine and traditional patient encounter groups across both pediatric and adult populations for malignant and nonmalignant hematological conditions. CONCLUSIONS: Evidence from this review suggests that telemedicine use in nonmalignant and malignant hematology provides similar or improved health care compared to face-to-face encounters in both pediatric and adult populations. Telemedicine interventions utilized in the included studies were well received in both pediatric and adult settings. However, more research is needed to determine the efficacy of implementing more widespread use of telemedicine for hematological conditions.

Telemedicine in Pediatrics: Systematic Review of Randomized Controlled Trials.

BACKGROUND: Telemedicine modalities, such as videoconferencing, are used by health care providers to remotely deliver health care to patients. Telemedicine use in pediatrics has increased in recent years. This has resulted in improved health care access, optimized disease management, progress in the monitoring of health conditions, and fewer exposures to patients with illnesses during pandemics (eg, the COVID-19 pandemic). OBJECTIVE: We aimed to systematically evaluate the most recent evidence on the feasibility and accessibility of telemedicine services, patients' and care providers' satisfaction with these services, and treatment outcomes related to telemedicine service use among pediatric populations with different health conditions. METHODS: Studies were obtained from the PubMed database on May 10, 2020. We followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. In this review, we included randomized controlled trials from the last 10 years that used a telemedicine approach as a study intervention or assessed telemedicine as a subspecialty of pediatric care. Titles and abstracts were independently screened based on the eligibility criteria. Afterward, full texts were retrieved and independently screened based on the eligibility criteria. A standardized form was used to extract the following data: publication title, first author's name, publication year, participants' characteristics, study design, the technology-based approach that was used, intervention characteristics, study goals, and study findings. RESULTS: In total, 11 articles met the inclusion criteria and were included in this review. All studies were categorized as randomized controlled trials (8/11, 73%) or cluster randomized trials (3/11, 27%). The number of participants in each study ranged from 22 to 400. The health conditions that were assessed included obesity (3/11, 27%), asthma (2/11, 18%), mental health conditions (1/11, 9%), otitis media (1/11, 9%), skin conditions (1/11, 9%), type 1 diabetes (1/11, 9%), attention deficit hyperactivity disorder (1/11, 9%), and cystic fibrosis-related pancreatic insufficiency (1/11). The telemedicine approaches that were used included patient and doctor videoconferencing visits (5/11, 45%), smartphone-based interventions (3/11, 27%), telephone counseling (2/11, 18%), and telemedicine-based screening visits (1/11, 9%). The telemedicine interventions in all included studies resulted in outcomes that were comparable to or better than the outcomes of control groups. These outcomes were related to symptom management, quality of life, satisfaction, medication adherence, visit completion rates, and disease progression. CONCLUSIONS: Although more research is needed, the evidence from this review suggests that telemedicine services for the general public and pediatric care are comparable to or better than in-person services. Patients, health care professionals, and caregivers may benefit from using both telemedicine services and traditional, in-person health care services. To maximize the potential of telemedicine, future research should focus on improving patients' access to care, increasing the cost-effectiveness of telemedicine services, and eliminating barriers to telemedicine use.

Genomic Survey of E. coli From the Bladders of Women With and Without Lower Urinary Tract Symptoms.

Urinary tract infections (UTIs) are one of the most common human bacterial infections. While UTIs are commonly associated with colonization by Escherichia coli, members of this species also have been found within the bladder of individuals with no lower urinary tract symptoms (no LUTS), also known as asymptomatic bacteriuria. Prior studies have found that both uropathogenic E. coli (UPEC) strains and E. coli isolates that are not associated with UTIs encode for virulence factors. Thus, the reason(s) why E. coli sometimes causes UTI-like symptoms remain(s) elusive. In this study, the genomes of 66 E. coli isolates from adult female bladders were sequenced. These isolates were collected from four cohorts, including women: (1) without lower urinary tract symptoms, (2) overactive bladder symptoms, (3) urgency urinary incontinence, and (4) a clinical diagnosis of UTI. Comparative genomic analyses were conducted, including core and accessory genome analyses, virulence and motility gene analyses, and antibiotic resistance prediction and testing. We found that the genomic content of these 66 E. coli isolates does not correspond with the participant's symptom status. We thus looked beyond the E. coli genomes to the composition of the entire urobiome and found that the presence of E. coli alone was not sufficient to distinguish between the urobiomes of individuals with UTI and those with no LUTS. Because E. coli presence, abundance, and genomic content appear to be weak predictors of UTI status, we hypothesize that UTI symptoms associated with detection of E. coli are more likely the result of urobiome composition.

Chronic circadian misalignment results in reduced longevity and large-scale changes in gene expression in Drosophila.

BACKGROUND: Circadian clocks are found in nearly all organisms, from bacteria to mammals, and ensure that behavioral and physiological processes occur at optimal times of day and in the correct temporal order. It is becoming increasingly clear that chronic circadian misalignment (CCM), such as occurs in shift workers or as a result of aberrant sleeping and eating schedules common to modern society, has profound metabolic and cognitive consequences, but the proximate mechanisms connecting CCM with reduced organismal health are unknown. Furthermore, it has been difficult to disentangle whether the health effects are directly induced by misalignment or are secondary to the alterations in sleep and activity levels that commonly occur with CCM. Here, we investigated the consequences of CCM in the powerful model system of the fruit fly, Drosophila melanogaster. We subjected flies to daily 4-h phase delays in the light-dark schedule and used the Drosophila Activity Monitoring (DAM) system to continuously track locomotor activity and sleep while simultaneously monitoring fly lifespan. RESULTS: Consistent with previous results, we find that exposing flies to CCM leads to a ~ 15% reduction in median lifespan in both male and female flies. Importantly, we demonstrate that the reduced longevity occurs independent of changes in overall sleep or activity. To uncover potential molecular mechanisms of CCM-induced reduction in lifespan, we conducted whole body RNA-sequencing to assess differences in gene transcription between control and misaligned flies. CCM caused progressive, large-scale changes in gene expression characterized by upregulation of genes involved in response to toxic substances, aging and oxidative stress, and downregulation of genes involved in regulation of development and differentiation, gene expression and biosynthesis. CONCLUSIONS: Many of these gene expression changes mimic those that occur during natural aging, consistent with the idea that CCM results in premature organismal decline, however, we found that genes involved in lipid metabolism are overrepresented among those that are differentially regulated by CCM and aging. This category of genes is also among the earliest to exhibit CCM-induced changes in expression, thus highlighting altered lipid metabolism as a potentially important mediator of the negative health consequences of CCM.