Reassessing the approach to informed consent: The case of unrelated hematopoietic stem cell transplantation in adult thalassemia patients

Introduction: The informed consent process is the legal embodiment of the fundamental right of the individual to make decisions affecting his or her health., and the patient's permission is a crucial form of respect of freedom and dignity, it becomes extremely important to enhance the patient's understanding and recall of the information given by the physician. This statement acquires additional weight when the medical treatment proposed can potentially be detrimental or even fatal. This is the case of thalassemia patients pertaining to class 3 of the Pesaro classification where Allogenic hematopoietic stem cell transplantation (HSCT) remains the only potentially curative treatment. Unfortunately, this kind of intervention is burdened by an elevated transplantation-related mortality risk (TRM: all deaths considered related to transplantation), equal to 30% according to published reports. In thalassemia, the role of the patient in the informed consent process leading up to HSCT has not been fully investigated. This study investigated the hypothesis that information provided by physicians in the medical scenario of HSCT is not fully understood by patients and that misunderstanding and communication biases may affect the clinical decision-making process.Methods: A questionnaire was either mailed or given personally to 25 patients. A second questionnaire was administered to the 12 physicians attending the patients enrolled in this study. Descriptive statistics were used to evaluate the communication factors.Results: The results pointed out the difference between the risks communicated by physicians and the risks perceived by patients. Besides the study highlighted the mortality risk considered to be acceptable by patients and that considered to be acceptable by physicians.Conclusions: Several solutions have been suggested to reduce the gap between communicated and perceived data. A multi-disciplinary approach may possibly help to attenuate some aspects of communication bias. Several tools have also been proposed to fill or to attenuate the gap between communicated and perceived data. But the most important tool is the ability of the physician to comprehend the right place of conscious consent in the relationship with the patient

Beta-thalassemia

Beta-thalassemias are a group of hereditary blood disorders characterized by anomalies in the synthesis of the beta chains of hemoglobin resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. The total annual incidence of symptomatic individuals is estimated at 1 in 100,000 throughout the world and 1 in 10,000 people in the European Union. Three main forms have been described: thalassemia major, thalassemia intermedia and thalassemia minor. Individuals with thalassemia major usually present within the first two years of life with severe anemia, requiring regular red blood cell (RBC) transfusions. Findings in untreated or poorly transfused individuals with thalassemia major, as seen in some developing countries, are growth retardation, pallor, jaundice, poor musculature, hepatosplenomegaly, leg ulcers, development of masses from extramedullary hematopoiesis, and skeletal changes that result from expansion of the bone marrow. Regular transfusion therapy leads to iron overload-related complications including endocrine complication (growth retardation, failure of sexual maturation, diabetes mellitus, and insufficiency of the parathyroid, thyroid, pituitary, and less commonly, adrenal glands), dilated myocardiopathy, liver fibrosis and cirrhosis). Patients with thalassemia intermedia present later in life with moderate anemia and do not require regular transfusions. Main clinical features in these patients are hypertrophy of erythroid marrow with medullary and extramedullary hematopoiesis and its complications (osteoporosis, masses of erythropoietic tissue that primarily affect the spleen, liver, lymph nodes, chest and spine, and bone deformities and typical facial changes), gallstones, painful leg ulcers and increased predisposition to thrombosis. Thalassemia minor is clinically asymptomatic but some subjects may have moderate anemia. Beta-thalassemias are caused by point mutations or, more rarely, deletions in the beta globin gene on chromosome 11, leading to reduced (beta+) or absent (beta0) synthesis of the beta chains of hemoglobin (Hb). Transmission is autosomal recessive; however, dominant mutations have also been reported. Diagnosis of thalassemia is based on hematologic and molecular genetic testing. Differential diagnosis is usually straightforward but may include genetic sideroblastic anemias, congenital dyserythropoietic anemias, and other conditions with high levels of HbF (such as juvenile myelomonocytic leukemia and aplastic anemia). Genetic counseling is recommended and prenatal diagnosis may be offered. Treatment of thalassemia major includes regular RBC transfusions, iron chelation and management of secondary complications of iron overload. In some circumstances, spleen removal may be required. Bone marrow transplantation remains the only definitive cure currently available. Individuals with thalassemia intermedia may require splenectomy, folic acid supplementation, treatment of extramedullary erythropoietic masses and leg ulcers, prevention and therapy of thromboembolic events. Prognosis for individuals with beta-thalassemia has improved substantially in the last 20 years following recent medical advances in transfusion, iron chelation and bone marrow transplantation therapy. However, cardiac disease remains the main cause of death in patients with iron overload

Production of dust by massive stars at high redshift

The large amounts of dust detected in sub-millimeter galaxies and quasars at high redshift pose a challenge to galaxy formation models and theories of cosmic dust formation. At z > 6 only stars of relatively high mass (> 3 Msun) are sufficiently short-lived to be potential stellar sources of dust. This review is devoted to identifying and quantifying the most important stellar channels of rapid dust formation. We ascertain the dust production efficiency of stars in the mass range 3-40 Msun using both observed and theoretical dust yields of evolved massive stars and supernovae (SNe) and provide analytical expressions for the dust production efficiencies in various scenarios. We also address the strong sensitivity of the total dust productivity to the initial mass function. From simple considerations, we find that, in the early Universe, high-mass (> 3 Msun) asymptotic giant branch stars can only be dominant dust producers if SNe generate <~ 3 x 10^-3 Msun of dust whereas SNe prevail if they are more efficient. We address the challenges in inferring dust masses and star-formation rates from observations of high-redshift galaxies. We conclude that significant SN dust production at high redshift is likely required to reproduce current dust mass estimates, possibly coupled with rapid dust grain growth in the interstellar medium.Comment: 72 pages, 9 figures, 5 tables; to be published in The Astronomy and Astrophysics Revie

Behavioral, neuropsychiatric and cognitive disorders in Parkinson's disease patients with and without motor complications

Background: Parkinson's disease (PD), commonly defined as a hypokinetic movement disorder, is hampered by the appearance of motor complications (MC), including dyskinesias and motor fluctuations, and non-motor symptoms such as behavioral, neuropsychiatric and cognitive disorders, which, in the last years, are gaining increasing attention. The factors affecting MC and these non-motor symptoms are still largely unknown and their interactions; are not yet fully evaluated. Objective: To identify the presence of behavioral, neuropsychiatric and cognitive disorders in PD patients with and without MC and to evaluate their association with MC. Methods: Consecutive PD patients received a comprehensive structured clinical evaluation including pharmacologic treatment, MC and non-motor symptoms such as reward-seeking behaviors, neuropsychiatric symptoms (depression, anxiety, psychoses and hallucinations) and dementia. Results: 349 patients were included in this analysis. Patient with MC showed enhanced frequency of dementia (p&lt;0.001), anxiety, depression and psychoses (p&lt;0.01). A higher frequency of impulse control disorders was detected in patients with dyskinesias (22.2% - p&lt;0.001) and motor complications (12.2% - p&lt;0.05). Dyskinesias were significantly more present in patients with hypersexuality (p&lt;0.05) and compulsive shopping (p&lt;0.001), while they were not significantly associated with pathological gambling and binge eating. Patients with dyskinesias also had significantly higher frequency of dopamine dysregulation syndrome, hallucinations and delusions (p&lt;0.001), with the exception of delusional jealousy. Discussion: We found a higher frequency of behavioral, neuropsychiatric and cognitive disorders in patients with MC. The lack of detection of dyskinesias in several PD patients with pathological gambling in our study represents a very interesting issue. While binge eating mainly seems to be related to the use of dopamine agonists, the significant lack of association between dyskinesias and delusional jealousy suggests the hypothesis of a possible underlying psychopathological predisposition rather than a mere pharmacologic effect in PD patients with these behavioral complications. (C) 2011 Elsevier Inc. All rights reserved