Epidemiology of clinically significant forms of alpha- and beta-thalassemia: A global map of evidence and gaps.

This systematic literature review assessed the global prevalence and birth prevalence of clinically significant forms of alpha- and beta-thalassemia. Embase, MEDLINE, and the Cochrane Library were searched for observational studies published January 1, 2000, to September 21, 2021. Of 2093 unique records identified, 69 studies reported across 70 publications met eligibility criteria, including 6 records identified from bibliography searches. Thalassemia prevalence estimates varied across countries and even within countries. Across 23 population-based studies reporting clinically significant alpha-thalassemia (e.g., hemoglobin H disease and hemoglobin Bart's hydrops fetalis) and/or beta-thalassemia (beta-thalassemia intermedia, major, and/or hemoglobin E/beta-thalassemia), prevalence estimates per 100 000 people ranged from 0.2 in Spain (over 2014-2017) to 27.2 in Greece (2010-2015) for combined beta- plus alpha-thalassemia; from 0.03 in Spain (2014-2017) to 4.5 in Malaysia (2007-2018) for alpha-thalassemia; and from 0.2 in Spain (2014-2017) to 35.7 to 49.6 in Iraq (2003-2018) for beta-thalassemia. Overall, the estimated prevalence of thalassemia followed the predicted pattern of being higher in the Middle East, Asia, and Mediterranean than in Europe or North America. However, population-based prevalence estimates were not found for many countries, and there was heterogeneity in case definitions, diagnostic methodology, type of thalassemia reported, and details on transfusion requirements. Limited population-based birth prevalence data were found. Twenty-seven studies reported thalassemia prevalence from non-population-based samples. Results from such studies likely do not have countrywide generalizability as they tended to be from highly specific groups. To fully understand the global prevalence of thalassemia, up-to-date, population-based epidemiological data are needed for many countries.

Endoscopic Findings in Patients with Moderate to Severe COVID-19: A Cross-sectional Study

Introduction: Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection has diverse gastrointestinal manifestations, often requiring endoscopy. Objective: The primary objective is to describe the need for endoscopic procedures from a sample of hospitalized patients with moderate to severe coronavirus disease 2019 (COVID-19). The secondary objective is to describe the characteristics, findings, and interventions. Materials and methods: An observational, descriptive, cross-sectional study was conducted from May 2020 to December 2021 about indications, endoscopic findings, interventions, anesthesia requirements, and adverse events from a sample of patients with moderate to severe COVID-19 in whom gastrointestinal endoscopic procedures were performed for any indication. Results: Of 2,312 hospitalized patients with moderate to severe COVID-19, 2.72% required endoscopic procedures, with a predominance of men (75%), an average age of 65.7 years, and the majority for upper gastrointestinal endoscopy (68%). The most frequent indications were gastrointestinal bleeding (62%) and enteral access (28.3%). An ischemic compromise was documented in three patients. Of those with digestive bleeding, 9.5% required hemostatic therapy, and 65% were on ventilatory support and sedation during the endoscopic procedure. In half of these cases, anesthesiology support was required without periprocedural adverse events, nor was a negative pressure room required in any procedure. Conclusions: In patients with moderate to severe COVID-19 requiring gastrointestinal endoscopy, clinical judgment is necessary to define the relevance of the procedure; in many cases, conservative management may be considered.

Introducción: la infección por coronavirus del síndrome respiratorio agudo grave de tipo 2 (SARS-CoV-2) tiene manifestaciones gastrointestinales diversas, que en muchas ocasiones requieren de endoscopia. Objetivo: como objetivo primario, describir la necesidad de procedimientos endoscópicos a partir de una muestra de pacientes hospitalizados con enfermedad por coronavirus de 2019 (COVID-19) moderado a grave, y como objetivo secundario, describir en detalle las características, los hallazgos y las intervenciones. Materiales y métodos: estudio observacional descriptivo de corte trasversal desde mayo de 2020 a diciembre de 2021 acerca de las indicaciones, hallazgos endoscópicos, intervenciones, requerimiento de anestesia y eventos adversos a partir de una muestra de pacientes con COVID-19 moderado a grave en quienes se realizaron procedimientos endoscópicos gastrointestinales por cualquier indicación. Resultados: de 2312 pacientes hospitalizados con COVID-19 moderado a grave, 2,72% requirió procedimientos endoscópicos, con predominio de los hombres (75%), edad promedio de 65,7 años y la mayoría para endoscopia digestiva alta (68%). Las indicaciones más frecuentes fueron hemorragia gastrointestinal (62%) y acceso enteral (28,3%). Se documentó compromiso isquémico en tres pacientes. En aquellos con sangrado digestivo, 9,5% requirió terapia hemostática, 65% se encontraba con soporte ventilatorio y sedación al momento del procedimiento endoscópico, y en la mitad de estos casos se requirió el apoyo de anestesiología, sin presentarse eventos adversos periprocedimentales, ni requerimiento de sala de presión negativa en ningún procedimiento. Conclusiones: en el paciente con COVID-19 moderado a grave con requerimiento de endoscopia gastrointestinal es necesario un juicio clínico para definir la pertinencia del procedimiento, y en muchos casos puede plantearse un manejo conservador.

Cost-sharing and adherence, clinical outcomes, health care utilization, and costs: A systematic literature review.

BACKGROUND: US health plans are adopting benefit designs that shift greater financial burden to patients through higher deductibles, additional copay tiers, and coinsurance. Prior systematic reviews found that higher cost was associated with reductions in both appropriate and inappropriate medications. However, these reviews were conducted prior to contemporary benefit design and medication utilization. OBJECTIVE: To assess the relationship and factors associated with cost-sharing and (1) medication adherence, (2) clinical outcomes, (3) health care resource utilization (HRU), and (4) costs. METHODS: A systematic review of literature published between January 2010 and August 2020 was conducted to identify the relationship between cost-sharing and medication adherence, clinical outcomes, HRU, and health care costs. Data were extracted using a standardized template and were synthesized by key questions of interest. RESULTS: From 1,995 records screened, 79 articles were included. Most studies, 71 of 79 (90%), reported the relationship between cost-sharing and treatment adherence, persistence and/or discontinuation; 16 (20%) reported data on cost-sharing and HRU or medication initiation, 11 (14%) on costsharing and health care costs, and 6 (8%) on cost-sharing and clinical outcomes. The majority of publications found that, regardless of disease area, increased cost-sharing was associated with worse adherence, persistence, or discontinuation. The aggregate data suggested the greater the magnitude of cost-sharing, the worse the adherence. Among studies examining clinical outcomes, cost-sharing was associated with worse outcomes in 1 study and the remaining 3 found no significant differences. Regarding HRU, higher-cost-sharing trended toward decreased outpatient and increased inpatient utilization. The available evidence suggested higher cost-sharing has an overall neutral to negative impact on total costs. Studies evaluating elimination of copays found either decreased or no impact in total costs. CONCLUSIONS: The published literature shows consistent impacts of higher cost sharing on initiation and continuation of medications, and the greater the cost-sharing, the worse the medication adherence. The evidence is limited regarding the impact of cost-sharing on clinical outcomes, HRU, and costs. Limited evidence suggests increased cost-sharing is associated with more inpatient care and less outpatient care; however, a neutral to no difference was suggested for other outcomes. Although increased costsharing is intended to decrease total costs, studies evaluating reducing or eliminating cost-sharing found that total costs did not rise. Today's growing cost-containment environment should carefully consider the broader impact cost-sharing has on treatment adherence, clinical outcomes, resource use, and total costs. It may be that cost-sharing is a blunt, rather than precise, tool to curb health care costs, affecting both necessary and unnecessary health care use. DISCLOSURES: This study and the development of this article were funded by the National Pharmaceutical Council. Mr Sils is an employee of the National Pharmaceutical Council. Dr Graff is a former employee of the National Pharmaceutical Council. Drs Fusco and Kistler and Ms Ruiz are employees of Xcenda. Xcenda received funding to conduct the literature review.

Analysis of COVID-19 on Diagnosis, Vaccine, Treatment, and Pathogenesis with Clinical Scenarios.

As the world continues to suffer from an ever-growing number of confirmed cases of the SARS-CoV-2 novel coronavirus, researchers are at the forefront of developing the best plan to overcome this pandemic through analyzing the pathogenesis, prevention, and treatment options pertaining to the virus. In the midst of a pandemic, the main route for detection of the virus has been conducting antigen tests for rapid results, using qRT-PCR, and conducting more accurate molecular tests, using rRT-PCR, on samples from patients. Most common treatments for those infected with COVID-19 include Remdesivir, an antiviral, dexamethasone, a steroid, and rarely, monoclonal antibody treatments. Although these treatments exist and are used commonly in hospitals all around the globe, clinicians often challenge the efficacy and benefit of these remedies for the patient. Furthermore, targeted therapies largely focus on interfering with or reducing the binding of viral receptors and host cell receptors affected by the SARS-CoV-2 novel coronavirus. In addition to treatment, the most efficacious method of preventing the spread of COVID-19 is the development of multiple vaccines that have been distributed as well as the development of multiple vaccine candidates that are proving hopeful in preventing severe symptoms of the virus. The exaggerated immune response to the virus proves to be a worrying complication due to widespread inflammation and subsequent clinical sequela. The medical and scientific community as a whole will be expected to respond with the latest in technology and research, and further studies into the pathogenesis, clinical implications, identification, diagnosis, and treatment of COVID-19 will push society past this pandemic.

A toolbox of immunoprecipitation-grade monoclonal antibodies to human transcription factors.

A key component of efforts to address the reproducibility crisis in biomedical research is the development of rigorously validated and renewable protein-affinity reagents. As part of the US National Institutes of Health (NIH) Protein Capture Reagents Program (PCRP), we have generated a collection of 1,406 highly validated immunoprecipitation- and/or immunoblotting-grade mouse monoclonal antibodies (mAbs) to 737 human transcription factors, using an integrated production and validation pipeline. We used HuProt human protein microarrays as a primary validation tool to identify mAbs with high specificity for their cognate targets. We further validated PCRP mAbs by means of multiple experimental applications, including immunoprecipitation, immunoblotting, chromatin immunoprecipitation followed by sequencing (ChIP-seq), and immunohistochemistry. We also conducted a meta-analysis that identified critical variables that contribute to the generation of high-quality mAbs. All validation data, protocols, and links to PCRP mAb suppliers are available at http://proteincapture.org.

Patient-reported outcomes in moderate-to-severe allergic asthmatics treated with omalizumab: a systematic literature review of randomized controlled trials.

OBJECTIVE: Randomized controlled trials (RCTs) have established the safety and efficacy of omalizumab on clinical parameters, and have also evaluated its impact on patient-reported outcomes (PROs). The purpose of this systematic literature review was to review published data based on PRO endpoints in order to determine the benefit of omalizumab as add-on therapy to inhaled corticosteroids in patients with moderate-to-severe persistent allergic asthma. METHODS: A systematic literature review was conducted of reference databases and recent conferences. RCTs of add-on omalizumab therapy in adults, adolescents, and children with moderate-to-severe persistent asthma were included. Two researchers independently screened and reviewed articles with regards to inclusion and exclusion criteria for relevant studies. RESULTS: Twenty-six trials met the criteria for inclusion. Of these, PRO measures were included in 19 trials to capture the impact of omalizumab on symptoms, 11 assessed patients for health-related quality-of-life (HRQoL), and four evaluated asthma control. Other PROs related to global evaluation of treatment effectiveness and work productivity. Overall, results demonstrated a significant difference across most PROs in favor of omalizumab add-on therapy vs placebo or comparators. CONCLUSIONS: PROs are an integral part of outcome assessment in clinical trials related to asthma. The RCTs reviewed demonstrate that omalizumab treatment improves PROs in patients with moderate-to-severe persistent allergic asthma, particularly symptom control and HRQoL.

Efficacy and safety of omalizumab in children and adolescents with moderate-to-severe asthma: A systematic literature review.

BACKGROUND: There are limited pediatric data about the use of omalizumab, especially the effectiveness and safety of omalizumab in the real-world management of allergic asthma. OBJECTIVE: The objective of this study was to summarize the safety and efficacy of omalizumab in both randomized clinical trials (RCT) used for U.S. Food and Drug Administration registration and real-world studies (RWS) based on clinical care of children with moderate-to-severe asthma. METHODS: Studies that evaluated omalizumab use in patients <18 years old and with asthma, published between January 2003 and October 2016, were retrieved from medical literature data bases. Assessed outcomes included the following: exacerbation rates, spirometric indices, changes in asthma medication use, asthma control, patient-reported outcomes, and health care resource utilization. RESULTS: A total of five RWS were identified; outcomes reported were compared with three omalizumab RCTs. Overall, the mean rate of annual exacerbations was significantly lower after 6 months to 2 years of treatment with omalizumab in both RCTs and RWS. In two RCTs and three RWS, inhaled corticosteroid use was significantly reduced in patients who used omalizumab. Similar reductions in the use of rescue medication were also observed in the RCTs and RWS on omalizumab. Real-world evidence demonstrated improvement in forced expiratory volume in the first second of expiration (% predicted) in patients treated with omalizumab as well as significant improvement in the level of asthma control observed over 1 year. There also was evidence that omalizumab treatment reduced health care resource utilization, including fewer hospitalizations, emergency department visits, and unscheduled medical visits. Safety outcomes in all five RWS showed no new safety signals and demonstrated that omalizumab was well tolerated. CONCLUSION: Overall, RCT evidence strongly supported omalizumab efficacy and safety as add-on treatment in children 6 to 11 years old with moderate-to-severe persistent allergic asthma. RWS data confirmed these findings in an extended patient population of children and adolescents that is more generalizable to the actual day-to-day management of these patients.

Direct medical costs and resource use for treating central and branch retinal vein occlusion in commercially insured working-age and Medicare populations.

PURPOSE: To quantify the burden of illness for incident branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO) in a commercially insured working-age (commercial) and Medicare US population. METHODS: Retrospective cohort analysis of health care claims from 2003 through 2008 from commercial and Medicare patients with ≥2 outpatient diagnoses for BRVO or CRVO. The index date was the first retinal vein occlusion diagnosis. Patients with medical and pharmacy benefits were followed ≥1 year preindex and then between 1 year and 3 years postindex. Incidence and prevalence of retinal vein occlusion was determined. Burden of illness was compared with matched control subjects without retinal vein occlusion. RESULTS: The commercial sample comprised 1,188 CRVO and 2,252 BRVO cases, whereas the Medicare sample had 2,739 CRVO and 4,573 BRVO cases. Adjusted ratio of case-to-control, all-cause expenditures for commercial patients at 1 year and 3 years postindex were 1.88 and 1.68, respectively, for BRVO and 1.42 and 1.36, respectively, for CRVO. For Medicare patients, these were 1.29 and 1.13, respectively, for BRVO and 1.23 and 1.14, respectively, for CRVO. All comparisons were significant (P < 0.001). CONCLUSION: Health care utilization and expenditures for commercially insured working-age and Medicare patients with BRVO or CRVO were significantly greater than those for control subjects. Retinal vein occlusion development may be a marker for the increased severity of systemic vascular disease.

Insulin use and persistence in patients with type 2 diabetes adding mealtime insulin to a basal regimen: a retrospective database analysis.

BACKGROUND: The objective of this study was to characterize insulin use and examine factors associated with persistence to mealtime insulin among patients with type 2 diabetes (T2D) on stable basal insulin therapy initiating mealtime insulin therapy. METHODS: Insulin use among patients with T2D initiating mealtime insulin was investigated using Thomson Reuters MarketScan® research databases from July 2001 through September 2006. The first mealtime insulin claim preceded by 6 months with 2 claims for basal insulin was used as the index event. A total of 21 months of continuous health plan enrollment was required. Patients were required to have a second mealtime insulin claim during the 12-month follow-up period. Persistence measure 1 defined non-persistence as the presence of a 90-day gap in mealtime insulin claims, effective the date of the last claim prior to the gap. Persistence measure 2 required 1 claim per quarter to be persistent. Risk factors for non-persistence were assessed using logistic regression. RESULTS: Patients initiating mealtime insulin (n = 4752; 51% male, mean age = 60.3 years) primarily used vial/syringe (87%) and insulin analogs (60%). Patients filled a median of 2, 3, and 4 mealtime insulin claims at 3, 6, and 12 months, respectively, with a median time of 76 days between refills. According to measure 1, persistence to mealtime insulin was 40.7%, 30.2%, and 19.1% at 3, 6, and 12 months, respectively. Results for measure 2 were considerably higher: 74.3%, 55.3%, and 42.2% of patients were persistent at 3, 6, and 12 months, respectively. Initiating mealtime insulin with human insulin was a risk factor for non-persistence by both measures (OR < 0.80, p < 0.01). Additional predictors of non-persistence at 12 months included elderly age, increased insulin copayment, mental health comorbidity, and polypharmacy (p < 0.05 for all). CONCLUSIONS: Mealtime insulin use and persistence were both considerably lower than expected, and were significantly lower for human insulin compared to analogs.

A retrospective database analysis of insulin use patterns in insulin-naïve patients with type 2 diabetes initiating basal insulin or mixtures.

OBJECTIVE: To describe insulin persistence among patients with type 2 diabetes initiating insulin therapy with basal insulin or insulin mixtures and determine factors associated with nonpersistence. RESEARCH DESIGN AND METHODS: The Thomson Reuters MarketScan((R)) databases were used to retrospectively analyze insulin-naïve patients with type 2 diabetes by initiating insulin therapy. Insulin use was described using a variety of measures. The persistence to insulin was described using both a gap-based measure and the number of claims measure. RESULTS: Patients in the basal insulin cohort (N = 15,255) primarily used insulin analogs (88.1%) and vial and syringe (97%). Patients in the mixture cohort (N = 2,732) were more likely to initiate on human insulin mixtures (62.5%) and vial and syringe (68.1%). Average time between insulin refills was 80 and 71 days for basal and mixture initiators, respectively. Nearly, 75% of basal insulin initiators and 65% of insulin mixture initiators had a 90-day gap in insulin prescriptions. More than half of all the patients had at least one insulin prescription per quarter. Patients initiating with insulin analogs were more likely to be persistent compared with those initiating with human insulin across both cohorts and measures of persistence (P < 0.001). CONCLUSION: Persistence to insulin therapy is poorer than one would anticipate, but appears to be higher in users of insulin analogs and insulin mixtures.

Productivity losses among treated depressed patients relative to healthy controls.

OBJECTIVES: Estimate the productivity-related cost of depression in an employed population. METHODS: By using administrative data, annual short-term disability (STD) and absenteeism costs ($2005) were compared for patients with depression and treated with antidepressants and for a matched control group without depression. RESULTS: Mean annual STD costs were $1038 among treated depressed patients versus $325 among controls and $1685 among a subgroup of severely depressed treated patients versus $340 among their controls. After controlling for demographic and employment characteristics, treated patients with depression had STD costs that were $356 higher per patient and those with severe depression had costs that were $861 higher. The marginal impact of treated depression on absenteeism was $377. CONCLUSIONS: Even when depressed patients are treated with antidepressants, there are substantial productivity losses. Therapies that can better manage depression may provide opportunities for savings to employers.

Impact of neutropenic complications on short-term disability in patients with cancer receiving chemotherapy.

OBJECTIVES: The study examined the impact of chemotherapy-induced neutropenic complications (CINC), defined as neutropenia with fever or infection, on short-term disability (STD) among cancer patients receiving chemotherapy. METHODS: The key outcome metrics were average monthly STD days and associated indirect costs. Patients with and without CINC were propensity score (PS) matched. Multivariate regressions were conducted on PS-matched cohorts to estimate the marginal impact of CINC. RESULTS: A total of 280 patients with CINC were PS-matched to 280 patients without CINC. Compared with matched patients, patients with CINC on average experienced 0.9 more STD day (3.2 vs. 2.3, p=0.046) and $155 more in indirect costs ($549 vs. 394, p=0.050) per month. After multivariate adjustment, patients with CINC experienced 1.0 more STD day (p=0.029), and incurred $200 more in indirect cost (p=0.016) per month. CONCLUSIONS: Patients with CINC experience significantly greater STD leave than patients with no neutropenic complications from cancer chemotherapy. The overall study sample only included patients from large self-insured employers in the US and may not reflect the work loss experience of all employed patients in the US or other countries. Indirect costs associated with absenteeism and presenteeism were not measured.