Sickle cell disease (SCD) is an inherited blood disorder that affects about 100,000 people in the U.S., primarily Blacks/African-Americans. A multitude of complications negatively impacts quality of ...life. Hydroxyurea has been FDA approved since 1998 as a disease-modifying therapy for SCD, but is underutilized. Negative and uninformed perceptions of hydroxyurea and barriers to its use hinder adherence and promotion of the medication. As the largest real-world study to date that assessed hydroxyurea use for children and adults with SCD, we gathered and analyzed perspectives of providers, individuals with SCD, and families. Participants provided information about socio-demographics, hospital and emergency admissions for pain, number of severe pain episodes interfering with daily activities, medication adherence, and barriers to hydroxyurea. Providers reported on indications for hydroxyurea, reasons not prescribed, and current laboratory values. We found that hydroxyurea use was reported in over half of eligible patients from this large geographic region in the U.S., representing a range of sickle cell specialty clinical settings and practices. Provider and patient/caregiver reports about hydroxyurea use were consistent with one another; adults 26 years and older were least likely to be on hydroxyurea; and the likelihood of being on hydroxyurea decreased with one or more barriers. Using the intentional and unintentional medication nonadherence framework, we found that, even for patients on hydroxyurea, challenges to taking the medicine at the right time and forgetting were crucial unintentional barriers to adherence. Intentional barriers such as worry about side effects and “tried and it did not work” were important barriers for young adults and adults. For providers, diagnoses other than HgbSS or HgbS-β0 thalassemia were associated with lower odds of prescribing, consistent with evidence-based guidelines. Our results support strengthening provider understanding and confidence in implementing existing SCD guidelines, and the importance of shared decision making. Our findings can assist providers in understanding choices and decisions of families; guide individualized clinical discussions regarding hydroxyurea therapy; and help with developing tailored interventions to address barriers. Addressing barriers to hydroxyurea use can inform strategies to minimize similar barriers in the use of emerging and combination therapies for SCD.
Previous global analyses, with known underdiagnosis and single cause per death attribution systems, provide only a small insight into the suspected high population health effect of sickle cell ...disease. Completed as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, this study delivers a comprehensive global assessment of prevalence of sickle cell disease and mortality burden by age and sex for 204 countries and territories from 2000 to 2021.
We estimated cause-specific sickle cell disease mortality using standardised GBD approaches, in which each death is assigned to a single underlying cause, to estimate mortality rates from the International Classification of Diseases (ICD)-coded vital registration, surveillance, and verbal autopsy data. In parallel, our goal was to estimate a more accurate account of sickle cell disease health burden using four types of epidemiological data on sickle cell disease: birth incidence, age-specific prevalence, with-condition mortality (total deaths), and excess mortality (excess deaths). Systematic reviews, supplemented with ICD-coded hospital discharge and insurance claims data, informed this modelling approach. We employed DisMod-MR 2.1 to triangulate between these measures—borrowing strength from predictive covariates and across age, time, and geography—and generated internally consistent estimates of incidence, prevalence, and mortality for three distinct genotypes of sickle cell disease: homozygous sickle cell disease and severe sickle cell β-thalassaemia, sickle-haemoglobin C disease, and mild sickle cell β-thalassaemia. Summing the three models yielded final estimates of incidence at birth, prevalence by age and sex, and total sickle cell disease mortality, the latter of which was compared directly against cause-specific mortality estimates to evaluate differences in mortality burden assessment and implications for the Sustainable Development Goals (SDGs).
Between 2000 and 2021, national incidence rates of sickle cell disease were relatively stable, but total births of babies with sickle cell disease increased globally by 13·7% (95% uncertainty interval 11·1–16·5), to 515 000 (425 000–614 000), primarily due to population growth in the Caribbean and western and central sub-Saharan Africa. The number of people living with sickle cell disease globally increased by 41·4% (38·3–44·9), from 5·46 million (4·62–6·45) in 2000 to 7·74 million (6·51–9·2) in 2021. We estimated 34 400 (25 000–45 200) cause-specific all-age deaths globally in 2021, but total sickle cell disease mortality burden was nearly 11-times higher at 376 000 (303 000–467 000). In children younger than 5 years, there were 81 100 (58 800–108 000) deaths, ranking total sickle cell disease mortality as 12th (compared to 40th for cause-specific sickle cell disease mortality) across all causes estimated by the GBD in 2021.
Our findings show a strikingly high contribution of sickle cell disease to all-cause mortality that is not apparent when each death is assigned to only a single cause. Sickle cell disease mortality burden is highest in children, especially in countries with the greatest under-5 mortality rates. Without comprehensive strategies to address morbidity and mortality associated with sickle cell disease, attainment of SDG 3.1, 3.2, and 3.4 is uncertain. Widespread data gaps and correspondingly high uncertainty in the estimates highlight the urgent need for routine and sustained surveillance efforts, further research to assess the contribution of conditions associated with sickle cell disease, and widespread deployment of evidence-based prevention and treatment for those with sickle cell disease.
Bill & Melinda Gates Foundation.
Background Food protein–induced enterocolitis syndrome (FPIES) is a non–IgE-mediated food allergy. FPIES diagnosis is frequently delayed because of the absence of classic allergic symptoms and lack ...of biomarkers. Objective We sought to characterize the clinical features and resolution of FPIES in patients evaluated in our practice. Methods Subjects 6 months to 45 years of age with FPIES were prospectively recruited for oral food challenges (OFCs). Medical records were searched to identify the subjects who did not participate in OFCs. Results Among 160 subjects, 54% were male; median age at diagnosis was 15 months. We performed 180 OFCs to 15 foods in 82 subjects; 30% of the study population had FPIES confirmed based on OFC results. The most common foods were cow's milk (44%), soy (41%), rice (22.5%), and oat (16%). The majority (65%) reacted to 1 food, 26% reacted to 2 foods, and 9% reacted to 3 or more foods. The majority were atopic, and 39% had IgE sensitization to another food. Thirty-nine (24%) subjects had positive specific IgE levels to the food inducing FPIES. Among children with specific IgE to cow's milk, 41% changed from a milk FPIES to an IgE-mediated phenotype over time. The median age when tolerance was established was 4.7 years for rice, 4 years for oat, and 6.7 years for soy. Median age when milk tolerance was established for subjects with undetectable milk-specific IgE levels was 5.1 years, whereas none of the subjects with detectable milk-specific IgE became tolerant to milk during the study ( P = .003). Conclusion FPIES typically resolves by age 5 years. Milk FPIES, especially with detectable food-specific IgE, can have a protracted course and eventually transition to acute reactions.
sPHENIX is a new experiment under construction for the Relativistic Heavy Ion Collider at Brookhaven National Laboratory which will study the quark-gluon plasma to further the understanding of ...quantum chromodynamics (QCP) matter and interactions. A prototype of the sPHENIX electromagnetic calorimeter (EMCal) was tested at the Fermilab Test Beam Facility in Spring 2018 as experiment T-1044. The EMCal prototype corresponds to a solid angle of <inline-formula> <tex-math notation="LaTeX">\Delta \eta \times \Delta \phi = 0.2 \times 0.2 </tex-math></inline-formula> centered at pseudo-rapidity <inline-formula> <tex-math notation="LaTeX">\eta = 1 </tex-math></inline-formula>. The prototype consists of scintillating fibers embedded in a mix of tungsten powder and epoxy. The fibers project back approximately to the center of the sPHENIX detector, giving 2-D projectivity. The energy response of the EMCal prototype was studied as a function of position and input energy. The energy resolution of the EMCal prototype was obtained after applying a position-dependent energy correction and a beam profile correction. Two separate position-dependent corrections were considered. The EMCal energy resolution was found to be <inline-formula> <tex-math notation="LaTeX">\sigma (E)/\langle E\rangle = 3.5(0.1) \oplus 13.3(0.2)/\sqrt {E} </tex-math></inline-formula> based on the hodoscope position-dependent correction, and <inline-formula> <tex-math notation="LaTeX">\sigma (E)/\langle E\rangle = 3.0(0.1) \oplus 15.4(0.3)/\sqrt {E} </tex-math></inline-formula> based on the cluster position-dependent correction. These energy resolution results meet the requirements of the sPHENIX physics program.
Organophosphorus (OP) compounds are detectable in the environment for years after use and endanger many populations. Although the effects of acutely toxic doses of many OP compounds are well ...described, much less is known about repeated low-level exposures. The purpose of these studies was to further evaluate potential toxicological effects of the extensively used OP pesticide chlorpyrifos (CPF) in rats. CPF, across a range of subthreshold doses (i.e., for acute toxicity), reduced rearing and sniffing activity and the magnitude of weight gain over 14 days of repeated exposure. Performance in a spatial learning task was impaired after 14 days of exposure to CPF (18.0 and 25.0 mg/kg) when testing was initiated 24 h after the last injection but not after a 14-day washout. However, inhibition of both fast anterograde and retrograde axonal transport was observed for up to 20 days after exposure to 25.0 mg/kg CPF. Studies using hippocampal cultures indicated that 8 days of continuous exposure to the parent compound, CPF (> or =100 micro M), resulted in cell toxicity and death. Furthermore, a dose (2.5 mg/kg) of CPF that had no effects on weight gain or memory performance when administered 5 days per week over 38 days impaired forelimb grip strength in the later days of testing. Collectively, these results indicate that repeated exposures to subthreshold doses of CPF may lead to growth retardation, behavioral abnormalities, and muscle weakness. Some of these symptoms may be attributed to effects of the OP on axonal transport.
The ACR BI-RADS experience: learning from history Burnside, Elizabeth S; Sickles, Edward A; Bassett, Lawrence W ...
Journal of the American College of Radiology,
12/2009, Letnik:
6, Številka:
12
Journal Article
Recenzirano
Odprti dostop
The Breast Imaging Reporting and Data System (BI-RADS) initiative, instituted by the ACR, was begun in the late 1980s to address a lack of standardization and uniformity in mammography practice ...reporting. An important component of the BI-RADS initiative is the lexicon, a dictionary of descriptors of specific imaging features. The BI-RADS lexicon has always been data driven, using descriptors that previously had been shown in the literature to be predictive of benign and malignant disease. Once established, the BI-RADS lexicon provided new opportunities for quality assurance, communication, research, and improved patient care. The history of this lexicon illustrates a series of challenges and instructive successes that provide a valuable guide for other groups that aspire to develop similar lexicons in the future.
The super Pioneering High Energy Nuclear Interaction eXperiment (sPHENIX) at the Relativistic Heavy Ion Collider will perform high-precision measurements of jets and heavy flavor observables for a ...wide selection of nuclear collision systems, elucidating the microscopic nature of strongly interacting matter ranging from nucleons to the strongly coupled quark-gluon plasma. A prototype of the sPHENIX calorimeter system was tested at the Fermilab Test Beam Facility as experiment T-1044 in the spring of 2016. The electromagnetic calorimeter (EMCal) prototype is composed of scintillating fibers embedded in a mixture of tungsten powder and epoxy. The hadronic calorimeter (HCal) prototype is composed of tilted steel plates alternating with the plastic scintillator. Results of the test beam reveal the energy resolution for electrons in the EMCal is <inline-formula> <tex-math notation="LaTeX">2.8\%\oplus 15.5\%/\sqrt {E} </tex-math></inline-formula> and the energy resolution for hadrons in the combined EMCal plus HCal system is <inline-formula> <tex-math notation="LaTeX">13.5\%\oplus 64.9\%/\sqrt {E} </tex-math></inline-formula>. These results demonstrate that the performance of the proposed calorimeter system satisfies the sPHENIX specifications.
Although there currently is no evidence of reduced breast cancer mortality for screening women at high risk with mammography, magnetic resonance (MR) imaging, or ultrasonography (US), the presumptive ...evidence of early cancer detection provided by numerous observational studies has led to the publication of guidelines and recommendations for the selective use of these imaging modalities. In general, annual screening mammography is recommended for women of appropriately high risk beginning at age 30 years, supplemental screening with MR imaging is recommended for a subset of women at very high risk, and screening US is suggested for women for whom MR imaging is appropriate but unavailable, impractical, or poorly tolerated. The use of screening US remains controversial among women who have no substantial risk factors other than dense breasts.
Fifty children who had symptomatic sickle cell disease received matched sibling marrow allografts between September 1991 and March 1999, with Kaplan-Meier probabilities of survival and event-free ...survival of 94% and 84%, respectively. Twenty-six patients (16 male, 10 female) had at least 2 years of follow-up after transplantation and were evaluated for late effects of transplantation and for its impact on sickle cell-related central nervous system (CNS) and pulmonary disease. Patients ranged between 3.3 and 14.0 (median, 9.4) years of age and had a median follow-up of 57.9 (range 38-95) months after transplantation. Among 22 of 26 patients who had stable donor engraftment, complications related to sickle cell disease resolved, and none experienced further episodes of pain, stroke, or acute chest syndrome. All 10 engrafted patients with a prior history of stroke had stable or improved cerebral magnetic resonance imaging results. Pulmonary function tests were stable in 22 of the 26 patients, worse in two, and not studied in two. Seven of eight patients transplanted for recurrent acute chest syndrome had stable pulmonary function. Linear growth measured by median height standard deviation score improved from −0.7 before transplantation to −0.2 after transplantation. An adverse effect of busulfan conditioning on ovarian function was demonstrated in five of seven evaluable females who are currently at least 13 years of age. None of the four males tested had elevated serum gonadotropin levels. These data confirm that allogenic bone marrow transplantation establishes normal erythropoiesis and is associated with improved growth and stable CNS imaging and pulmonary function in most patients.
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