Absence Of Curative Treatment Research Articles

Parents' dilemma: A therapeutic decision for children with spinal muscular atrophy (SMA) type 1.

SMA type 1 is a severe neurodegenerative disorder that, in the absence of curative treatment, leads to death before 1 year of age without ventilatory support. Three innovative therapies are available to increase life expectancy. (i) To increase knowledge about parents' experiences with their decision to have opted for an innovative therapy; (ii) to assess the middle-term psychological consequences in the parents' lives. We used an in-depth interview; a self-administrated questionnaire and self-report scales (BDI-II, STAI-Y, PSI-SF, SOC-13, PBA, DAS 16 and FICD). We compared parents hesitant before the decision to parents who were not-hesitant and the group of parents whose child was treated with gene therapy (GT) to parents whose child received another innovative therapy. We included n = 18 parents of 13 children. Parent's mean age was 34.7 (±5.2), child's average age was 44.3 months (±38.0). Retrospectively, most parents felt involved by doctors in decision-making on treatment, they felt their point of view was considered and were satisfied with the effects of the treatment. The group of parents "non-hesitant" was more depressed (p < 0.001), more anxious (p = 0.022) and had higher parental stress (p = 0.026) than the group of "hesitant" parents; the group of "GT-treated" parents was more depressed (p = 0.036) than the group of parents with "other therapy". Qualitative data highlights revealed: the need to save the child's life at all costs; the fear of coping with end of life and palliative care, the high value of perceived physician confidence in the treatment, the hope that the child will acquire autonomy or be cured. At the time of the decision, no parents felt they fully understood all of the issues regarding therapy and the disease. Hesitating before making a decision did not predispose parents to depression and anxiety. The narratives suggest that the parents faced a dilemma regarding their child's health in an urgent context. The decision was not final, and parents will continue to think about it throughout the care process.

Common needs in uncommon conditions: a qualitative study to explore the need for care in pediatric patients with rare diseases

BackgroundChallenges faced by children diagnosed with a rare disease or complex condition and their family members are often characterized by disease-specific complexities, such as a prolonged diagnostic process, an uncertain prognosis, and the absence of curative treatment. The psychological burden of living with a rare disease or complex condition is often understudied and may present overarching concepts that shape the general experience of having been diagnosed with a rare condition. The present study examines common needs from a comprehensive perspective combining relevant aspects from the rare disease literature in a theoretical perspective from pediatric psychology, such as a family-centred, developmental and interdisciplinary approach. An exploratory study was designed among parents from children with a rare disease or complex condition in an Integrated University Children’s Hospital in the Netherlands. Semi-structured interviews were conducted with open-ended questions based around the experience of having a child diagnosed with a rare condition, such as the psychosocial impact on the child and it’s development, the impact on the family, and how provided care was experienced.ResultsTwelve interviews were analysed with a thematic content analysis to identify common needs. Eight themes followed from the analysis and uncovered the need for (1) family-focused care, (2) coping with uncertainty, (3) empathic communication, (4) practical support, (5) information, (6) psychological support, (7) interdisciplinary care, and (8) social support.ConclusionsThe results from our study provide directions for research and health care to support young patients with a rare disease or complex condition and their families. Moreover, our results demonstrated that there are overarching concepts across different rare diseases that may be optimally supported with interdisciplinary care.

Information provision to older patients receiving palliative chemotherapy: a quality study

ObjectivesCancer treatment has become increasingly successful. However, prolonging and preserving life has become an important goal of therapy since many patients generally receive palliative chemotherapy. The perception of life changes...

Sleep apnoea and cognitive impairment: myth or reality?

A growing number of studies in animal models have highlighted the link between sleep disorders and Alzheimer's disease (AD). In the absence of curative treatment, it is therefore important to consider any comorbidities that may influence the course of AD such as obstructive sleep apnoea-hypnoea (OSAH) and its syndrome (OSAHS), which appear to be potentially interesting because it occurs frequently, it is treatable and it is often associated with cognitive impairment. The association between OSAH/OSAHS and cognition is variable across studies, but OSAH/OSAHS is more common in older patients with AD than in cognitively normal individuals. OSAH/OSAHS is often associated with the subsequent development of mild cognitive impairment and AD. Although there is no evidence that treatment of OSAH/OSAHS in AD would have a major impact on the course of the disease, treatment would appear to improve cognition in AD patients with OSAH/OSAHS. Finally, the literature suggests a link between OSAH/OSAHS and AD biomarkers. Taken together, these data highlight the importance of detecting and treating OSAHS in this population.

Long-acting antiretrovirals: a new era for the management and prevention of HIV infection.

The long-acting antiretroviral cabotegravir and rilpivirine combination has just received FDA, EMA and Health Canada approval. This novel drug delivery approach is about to revolutionize the therapy of people living with HIV, decreasing the 365 daily pill burden to only six intramuscular injections per year. In addition, islatravir, a first-in-class nucleoside reverse transcriptase translocation inhibitor, is intended to be formulated as an implant with a dosing interval of 1 year or more. At present, long-acting antiretroviral therapies (LA-ARTs) are given at fixed standard doses, irrespectively of the patient’s weight and BMI, and without consideration for host genetic and non-genetic factors likely influencing their systemic disposition. Despite a few remaining challenges related to administration (e.g. pain, dedicated medical procedure), the development and implementation of LA-ARTs can overcome long-term adherence issues by improving patients’ privacy and reducing social stigma associated with the daily oral intake of anti-HIV treatments. Yet, the current ‘one-size-fits-all’ approach does not account for the recognized significant inter-individual variability in LA-ART pharmacokinetics. Therapeutic drug monitoring (TDM), an important tool for precision medicine, may provide physicians with valuable information on actual drug exposure in patients, contributing to improve their management in real life. The present review aims to update the current state of knowledge on these novel promising LA-ARTs and discusses their implications, particularly from a clinical pharmacokinetics perspective, for the future management and prevention of HIV infection, issues of ongoing importance in the absence of curative treatment or an effective vaccine.

Sleep apnea and cognitive impairment: Myth or reality?

A growing number of studies in animal models have highlighted the link between sleep disorders and Alzheimer's disease (AD). In the absence of curative treatment, it is therefore important to consider any comorbidities that may influence the course of AD such as Obstructive sleep apnea-hyponea (OSAH) and its syndrome (OSAHS), which appear to be potentially interesting because it is frequent, treatable and often associated with cognitive impairment. The association between OSAH/OSAHS and cognition is variable across studies, but OSAH/OSAHS is more common in older patients with AD than in cognitively normal individuals. OSAH/OSAHS is often associated with the subsequent development of mild cognitive impairment and AD. Although there is no evidence that treatment of OSAH/OSAHS in AD would have a major impact on the course of the disease, treatment would appear to improve cognition in AD patients with OSAH/OSAHS. Finally, the literature suggests a link between OSAH/OSAHS and AD biomarkers. Together, these data highlight the importance of detecting and treating OSAHS in this population.

Epidermolysis bullosa.

Epidermolysis bullosa (EB) is an inherited, heterogeneous group of rare genetic dermatoses characterized by mucocutaneous fragility and blister formation, inducible by often minimal trauma. A broad phenotypic spectrum has been described, with potentially severe extracutaneous manifestations, morbidity and mortality. Over 30 subtypes are recognized, grouped into four major categories, based predominantly on the plane of cleavage within the skin and reflecting the underlying molecular abnormality: EB simplex, junctional EB, dystrophic EB and Kindler EB. The study of EB has led to seminal advances in our understanding of cutaneous biology. To date, pathogenetic mutations in 16 distinct genes have been implicated in EB, encoding proteins influencing cellular integrity and adhesion. Precise diagnosis is reliant on correlating clinical, electron microscopic and immunohistological features with mutational analyses. In the absence of curative treatment, multidisciplinary care is targeted towards minimizing the risk of blister formation, wound care, symptom relief and specific complications, the most feared of which - and also the leading cause of mortality - is squamous cell carcinoma. Preclinical advances in cell-based, protein replacement and gene therapies are paving the way for clinical successes with gene correction, raising hopes amongst patients and clinicians worldwide.

Abstract 3514: DNA methylation markers for risk of metastasis in a cohort of men with localized prostate cancer

Abstract Background: Most localized prostate cancers (PCa) are indolent and will not require treatment, but a small proportion can progress to metastasis. Distinguishing aggressive from indolent tumors can better inform treatment decisions. There has been interest in cancer genomics to predict PCa aggressiveness but with no consensus on methylation's role. We examined whether DNA methylation status of selected candidate genes can predict risk of PCa metastasis in the absence of curative treatment. Methods: A retrospective cohort of men diagnosed with PCa at Kaiser Permanente Southern California 1997-2007 who met the following inclusion criteria were identified: (1) diagnosed at stage I and II and (2) did not receive PCa treatment for at least 6 months after diagnosis. Men were followed for metastasis and censored at the initiation of prostatectomy or radiation, non-PCa related death, membership termination, or end of 2016. Potential metastasis was identified by an algorithm, then manually reviewed and confirmed. For each metastasis case, up to 4 controls were selected using density sampling, matched on age, race (black vs. non-black) and Gleason grade. For each case and control, FFPE blocks of diagnostic prostate biopsy cores were retrieved. The study pathologists reviewed the H/E slides and circled cancerous areas, which were macro-dissected for DNA extraction. Methylation status was obtained using Illumina's Infinium Methylation EPIC BeadChip. The candidate genes (N=118) were selected from the literature in the functional categories of cell cycle control; tumor suppressors; cell signaling; cell adhesion; angiogenesis; immune function; and stem cell markers. In total, 4,518 CpG markers from the Infinium assay covered regions of the candidate genes. Three statistical methods were used to detect the genetic associations, including univariate, principal components (PC)-based, and cluster-based analysis. To adjust for multiple comparisons within a gene and across genes, a double false discovery rate (DFDR) procedure was applied. The DFDR-adjusted p-value for each marker was calculated at 0.05 alpha level. Results: In total 163 cases and 311 matched controls were included in the analyses after excluding those with insufficient DNA or that failed the assay. For each analysis, univariate, PC-based, and cluster-based, the following number of candidate genes were found significant after DFDR procedure: 5 genes (PLAU, RASSF1, SLC5A6, KDR, CCL2), 8 genes (BCL2, KLF4, CTNND2, NRP2, RAP1GAP, LPL, EFEMP1, HSPA1A), and 7 genes (ETV4, ANGPTL4, BRMS1, LPL, BCL2, NANOG, ADM), respectively. The overall agreement of gene-level testing significances was at 84% between PC-based and cluster-based analysis. Conclusions: Among those showing consistent statistical significance, two genes, BCL2 and LPL, were identified in two analyses. Further study may provide insight to predict risk of prostate cancer metastasis. Citation Format: Kim Cannavale, Jeff Slezak, Yu-Hsiang Shu, Gary W. Chien, XuFeng Chen, Feng Shi, Kim Siegmund, Stephen Van Den Eeden, Jiaoti Huang, Chun R. Chao. DNA methylation markers for risk of metastasis in a cohort of men with localized prostate cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3514.

Survival and mortality of elderly men with localized prostate cancer managed with primary androgen deprivation therapy or by primary observation

BackgroundAndrogen deprivation therapy (ADT) remains a primary treatment for localized prostate cancer (PCa) even though there is no evidence that its use is beneficial in the absence of curative treatment.MethodsMen aged ≥70 years (n = 16,534) diagnosed with localized PCa from 1985 to 2014 and managed either with primary observation or ADT in the absence of curative treatment were included. The cases were identified from the population-based Finnish Cancer Registry. We estimated the standardized mortality ratios (SMR) for overall mortality by treatment group. We determined the relative risk (RR) of PCa-specific mortality (PCSM) and other-cause mortality between the two treatment groups. Survival was determined using the life table method. Two age groups (70–79 years and ≥ 80 years) and three calendar time cohorts (1985–1994, 1995–2004, and 2005–2014) were compared following adjustment of propensity score matching between the treatment groups with four covariates (age, year of diagnosis, educational level, and hospital district). Follow-up continued until death or until December 31, 2015.ResultsPatients in the observation group had lower overall SMRs than those in the ADT group in both age cohorts over the entire study period. PCSM was higher in men aged 70–79 years undergoing primary ADT compared to those managed by observation only (RR: 1.70, 95% confidence interval [CI]: 1.29–2.23 [1985–1994]; RR 1.55, 95% CI: 1.35–1.84 [1995–2004]; and RR 2.71, 95% CI: 2.08–3.53 [2005–2014]); p = 0.005 for periodic trend. A similar trend over time was also observed in men aged > 80 years; (p for age–period interaction = 0.237). Overall survival was also higher among men in their 70’s managed by observation compared to those undergoing ADT.ConclusionsPrimary ADT within four months period from diagnosis is not associated with improved long-term overall survival or decreased PCSM compared to primary conservative management for men with localized PCa. However, this observational study’s conclusions should be weighted with confounding factors related to cancer aggressiveness and comorbidities.

Palliative Care in SMA Type 1: A Prospective Multicenter French Study Based on Parents' Reports

Spinal muscular atrophy type 1 (SMA-1) is a severe neurodegenerative disorder, which in the absence of curative treatment, leads to death before 1 year of age in most cases. Caring for these short-lived and severely impaired infants requires palliative management. New drugs (nusinersen) have recently been developed that may modify SMA-1 natural history and thus raise ethical concerns about the appropriate level of care for patients. The national Hospital Clinical Research Program (PHRC) called “Assessment of clinical practices of palliative care in children with Spinal Muscular Atrophy Type 1 (SMA-1)” was a multicenter prospective study conducted in France between 2012 and 2016 to report palliative practices in SMA-1 in real life through prospective caregivers' reports about their infants' management. Thirty-nine patients were included in the prospective PHRC (17 centers). We also studied retrospective data regarding management of 43 other SMA-1 patients (18 centers) over the same period, including seven treated with nusinersen, in comparison with historical data from 222 patients previously published over two periods of 10 years (1989–2009). In the latest period studied, median age at diagnosis was 3 months [0.6–10.4]. Seventy-seven patients died at a median 6 months of age[1–27]: 32% at home and 8% in an intensive care unit. Eighty-five percent of patients received enteral nutrition, some through a gastrostomy (6%). Sixteen percent had a non-invasive ventilation (NIV). Seventy-seven percent received sedative treatment at the time of death. Over time, palliative management occurred more frequently at home with increased levels of technical supportive care (enteral nutrition, oxygenotherapy, and analgesic and sedative treatments). No statistical difference was found between the prospective and retrospective patients for the last period. However, significant differences were found between patients treated with nusinersen vs. those untreated. Our data confirm that palliative care is essential in management of SMA-1 patients and that parents are extensively involved in everyday patient care. Our data suggest that nusinersen treatment was accompanied by significantly more invasive supportive care, indicating that a re-examination of standard clinical practices should explicitly consider what treatment pathways are in infants' and caregivers' best interest. This study was registered on clinicaltrials.gov under the reference NCT01862042 (https://clinicaltrials.gov/ct2/show/study/NCT01862042?cond=SMA1&rank=8).

Advances in pathophysiology and neuroimaging: Implications for sleep and dementia.

The burden of dementia is increasing globally. In the absence of curative treatment, preventive strategies to delay or reduce progression of dementia are crucial. This relies on the identification of modifiable risk factors. The effects of dementia on sleep are well recognized; however, there is now growing evidence suggesting a bidirectional relationship between sleep pathologies and dementia. SDB, poor quality sleep and extremes of sleep duration are commonly experienced by both middle-aged and older populations. All have been associated with increased risk of dementia and cognitive decline in a number of observational studies, albeit inconsistently. The mechanisms by which these sleep disorders may contribute to neurodegeneration are manifold, and include impacts of fragmented sleep on the clearance of neurotoxins, and in SDB by the additive effects of intermittent hypoxia on beta-amyloid production, hypoxic cell death, neuroinflammation and damage to cerebral vasculature. Untangling the mechanisms by which sleep pathologies may impact risk of dementia is a challenge. Many insights into the pathophysiology of these relationships have been derived from animal- and population-based studies. Neuroimaging modalities offer important opportunities to further understand the link between sleep pathologies and dementia risk in vivo, especially in the critical preclinical phase of AD. In this review, we canvas updates in dementia pathophysiology, the evidence linking sleep pathologies with dementia and outline the advances in determining this potential pathophysiological link that have eventuated from the application of neuroimaging.

Decision-Making Regarding Ventilator Support in Children with SMA Type 1-A Cross-Sectional Survey among Physicians.

Spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by muscle atrophy and severe proximal muscle weakness. In the absence of curative treatment, it has been controversial whether critically ill infants with SMA type 1 should receive ventilator support. The aim of this study was to investigate the process of decision-making regarding ventilator support in children with SMA type 1 from the perspectives of physicians. A web-based survey with 17 questions and 2 case vignettes was conducted in 671 physicians in Germany and Switzerland from 12/2016 to 03/2017. The survey focused on factors influencing the decision about ventilator support and the content in informed consent discussions. Additionally, physicians were asked about their general attitude towards mechanical ventilation in children with SMA type 1 and their hypothetical clinical management in emergency settings using case vignettes. Hundred and sixty-five physicians participated in the survey (50.3% child neurologists, 18.8% specialists for ventilator support, 6.1% pediatric palliative care physicians, and 6.1% with more than one of these specializations). Of all physicians, 44.2% confirmed to have experience with SMA type 1 patients using ventilator support. In summary, our results show that physicians' attitudes and experiences about mechanical ventilation in children with SMA type 1 vary considerably and are likely to influence the outcome in informed consent discussions and the hypothetical management in emergency settings.

Changes in health-related quality of life in oesophagogastric cancer patients participating in palliative and curative therapies

Background: Various treatments are used to prolong survival and improve quality of life (QOL). The purpose of this study was to assess the change in QOL scores in patients with Oesophagogastric (OG) cancer undergoing curative intent and palliative therapy. Methods: This was a mix-designed cohort study with a consecutive sampling of patients with OG cancer who underwent curative or palliative treatment regimens. The QOL, as a determinant of efficacy and impact of cancer care, was evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires. QOL data were collected from the eligible subjects at three points of time. The repeated measurement test was used to compare the significance of change in scores. Results: Overall, 149 patients (54.4% male, 61.1% curative intent, 52.3% esophageal, 37.6 % gastric, 10.1% OG junction cancer; with mean age 62 year) with OG cancer were eligible for inclusion in the study. Compared to the palliative group, the curative group was more likely to have an esophageal tumor site, Squamous Cell Carcinoma, and stage 2 (versus stomach, Adenocarcinoma, and stage 4 in the palliative group). In comparing the patients' functional, global health status, and cancer symptom, considering time, group of treatment, and their mutual effect the result indicated significant difference between the intervention groups. Conclusion: Most patients with Oesophagogastric cancer are diagnosed with an incurable form of the disease. Hence in absence of curative treatment, palliative therapy is the most effective therapy to maintain patient independency and relieve pain and symptom in order to improve their QOL. The present study has shown that palliative similar to curative intervention can improve the QOL in cancer patient especially in short term.

The Scale of instantaneous wellbeing: validity in a population with major neurocognitive disorders.

The quality of life (QoL) of people with a neurodegenerative pathology is a major issue in the absence of curative treatment. However, validated tools, suitable for patients with major neurocognitive disorders at a severe stage are rare and time-consuming in routine. The aim of this study is to analyze the validity of convergence and the reliability over time of a visual analog scale of well-being named EVIBE (Échelle d'évaluation instantanée de bien-être). The correlation between the EVIBE and another quality of life scale, the Qol-Ad was studied. The correlation with other scales expected to vary with QoL was also studied with the EQ-5D for the measurement of the state of health felt and the NPI-ES for the measurement of behavioral disorders. The EVIBE was administered twice, a few minutes apart, to measure its reliability over time. One hundred and thirty-five patients with Alzheimer's disease or a related disorder were recruited. The results indicated a significant correlation with Qol-AD (r=0.54, p< 0.001). The correlation remained significant when the Mini mental state examination was less than 10 (r=0.39, p=0.05). Correlations between EVIBE and EQ-5D and NPI-ES indicated more mixed results with significant correlation only for the analog part of the EQ-5D (r=0.34, p=0.007). The comparison between the two EVIBEs a few minutes apart showed a satisfactory agreement (r=0.52, p> 0.001). This study shows that EVIBE present a good convergence validity and a good reliability over time to measure the QoL of patients with neurodegenerative pathology even at severe stages of the disease. The scale allows a direct and rapid assessment of the QoL of patients in routine.

Maladie de Huntington : données actuelles sur la prise en charge thérapeutique des troubles psychiatriques

ObjectiveHuntington's disease is a neurodegenerative genetic, autosomal dominant disease. George Huntington describes this trouble in 1872. In 1993, scientist founded mutation on IT15 gene on 4th chromosome. Prevalence in France is 1/10 000 without sex predominance or race. The main symptoms are: choreic movements, axial impairment, psychiatric disorders and the presence of cognitive impairment. The diagnostic is clinic, genetic and radiologic. Despite the absence of curative treatment, symptomatic care supports deficit symptoms of the pathology, thus improves the quality of life of patients. In the context of a comprehensive and optimal therapy, health professionals provide recommendations for guidelines like Huntington's disease national reference center in August 2015. We will define diagnostic and clinical aspects of Huntington's disease, and then we will focus our analysis on the psychiatric aspect. Material and methodFirst, we will illustrate management provided by our teams. Patient A had positive diagnostic of Huntington's disease and personal psychiatric antecedent of depression. She was hospitalized in neurological unit for a panic attack in August 2015. They give tetrabenazine and to prevent depressive effect we prescribed antidepressant first (serotonin–norepinephrine reuptake inhibitor), then antipsychotic (risperidone, then haloperidol) and benzodiazepine. Patient B had Huntington's disease in family and personal diagnostic of Huntington's disease and personal psychiatric antecedent of depression. She was admitted in psychiatric unit for psychotic symptom. She received antipsychotic (risperidone) and antidepressant (venlafaxine) with benzodiazepine. Both of them had clinical improvement. Patient A, went to reeducation care, patient B went home with nurse. When we analyzed literature on the psychiatric therapeutic in Huntington's disease with review, we found that apathy is the most psychiatric symptom in Huntington's disease (50–80% Inserm). Benzodiazepine had good result for anxiety. We must search and treat psychiatric disorder like depression and mood disorder. Irritability and anxiety are symptoms of mood disorder and can be treated with antidepressive and mood stabilizer. Suicide is an emergency because of the mortality rate. The guideline is the same of suicide in psychiatric emergency. Antipsychotics are not avoided and used for choreic and psychotic symptoms (delirium, hallucination…) but second generation antipsychotics are generally preferable because of the lesser presence of adverse event. ResultsThe use of selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitor (SNRI) for moods sign are the most frequently used therapy reference. Electroconvulsive therapy (ECT) and mood stabilizer have similar results to those obtained in mood disorders without neurodegenerative pathology. Antipsychotic like risperidone or olanzapine are good requirements. Guidelines of Huntington's disease national reference center and literature give these therapeutic choices. With our two patients, we can see clinical improvement and the main objective was return home. Literature explain important role of psychotherapy, social, diet and hygiene habits. We must have global care like other psychiatric patient and more because of neurological reach. ConclusionThe implementation of classical specific therapeutic in psychiatry improves these symptoms and optimizes the quality of life for our patients. A comprehensive and multidisciplinary support involving medical and paramedical rehabilitation is a necessity to take into account.

Red blood cell transfusions for thalassemia: results of a survey assessing current practice and proposal of evidence‐based guidelines

In the absence of curative treatment, such as stem cell transplant, regular transfusions remain the mainstay of therapy for individuals with thalassemia major, a syndrome that results from marked ineffective erythropoiesis and the resultant anemia. The primary objectives of transfusion therapy are twofold: to suppress ineffective erythropoiesis and to ensure appropriate growth and development through childhood. In practice, a number of different transfusion protocols are in use across the developed world, with on-demand transfusion still being the paradigm in most of the developing world with limited resources. To investigate perceived differences in transfusion practice, a self-reported electronic survey was disseminated to eight US thalassemia treatment centers in February 2011. The survey was divided into sections ranging from laboratory and clinical practices to emerging transfusion-transmitted diseases. The survey response rate was 100%. The total number of transfused patients was 411. One-hundred percent of institutions used leukoreduced blood. No centers routinely provided cytomegalovirus-seronegative red blood cells (RBCs). Half the centers provided irradiated RBCs; only one routinely provided washed RBCs, and none transfused RBCs of defined storage age. Seventy-five percent of centers routinely phenotyped thalassemia patients' RBC antigens; 50% prophylactically matched for Rh and K antigens. The frequency of antibody investigations varied widely, and 25% of centers routinely medicated patients before transfusion. Eight thalassemia centers in the United States were surveyed to determine the uniformity of transfusion practice. The variability of the results was surprising. Consequently, we performed a literature review and propose an evidence-based protocol for routine transfusion therapy for patients with thalassemia.

Locally Advanced Prostate Cancer: Optimal Therapy in Older Patients

There is no standard treatment for locally advanced prostate cancer. Even the definition is still unclear. Locally advanced disease may refer to over-staged well-curable tumors as well as to advanced and probably incurable cancers. Similar uncertainties are present regarding the definition of 'old' in this context. Conservatively treated locally advanced prostate cancer is associated with poor survival outcome. With the increasing life expectancy, in the absence of curative treatment, even patients in their ninth decade of life may later suffer from symptoms of aggressive prostate cancer and are at a high risk of death from prostate cancer that might be prevented at least in part by early intervention. On the other hand, functional results after prostate cancer treatment are worse in elderly patients. In this article we discuss aspects of the management of locally advanced prostate cancer in the elderly with special focus on the recommendation of current clinical guidelines.

194th ENMC international workshop. 3rd ENMC workshop on exon skipping: Towards clinical application of antisense-mediated exon skipping for Duchenne muscular dystrophy 8–10 December 2012, Naarden, The Netherlands

194th ENMC international workshop. 3rd ENMC workshop on exon skipping: Towards clinical application of antisense-mediated exon skipping for Duchenne muscular dystrophy 8–10 December 2012, Naarden, The Netherlands

Linfangioleiomiomatosis

Lymphangioleiomyomatosis (LAM) is a rare disease that mainly affects women, particularly at fertile age. It is sporadic or associated with tuberous sclerosis complex. It is characterised by an abnormal proliferation of immature smooth muscle cells (SMC), which grow aberrantly in the airway, parenchyma, lymphatics and pulmonary blood vessels and which can gradually lead to respiratory failure. It affects several systems, affecting the lymphatic ganglia and causing abdominal tumours. Given its very low prevalence, a difficult to establish early diagnosis, absence of curative treatment and the difficulty in obtaining information, places LAM under the heading of the so-called Rare Diseases. There is a growing interest in the study of this disease which has led to the setting up of patient registers and an exponential growth in LAM research, both at a clinical level and cellular level.

Early prevention at public health issue.

Alzheimer's Disease and related disorders have recently become a priority in France and two consecutive governmental plans have been undertaken in 2001-2004 and 2004-2007. The number of prevalent cases was estimated to be 850,000 in France with an incidence of 220,000 cases. Only 50% of these cases were actually diagnosed and about 32% were treated by antidementia drugs. If the incidence and the duration of the disease do not change, the number of cases will increase to 1,200,000 in 2020 and 2,100,000 cases in 2040. In absence of curative treatment, the prevention way is necessary if one wishes to control this phenomena. The development of Memory Clinics and "Centres de Mémoires de Ressources et de Recherche" in all regions in France is one of the important measures to develop primary and secondary prevention in subjects with cognitive complaints or MCI. Several factors could be the basis of this prevention 1) Vascular risk factors (High Blood Pressure, Diabetes, Obesity, Hypercholesterolemiae, Tobacco consumption) ; 2) physical exercise ; 3) Stimulating cognitive activities ; 4) Nutrition ; 5) depressive disorders and loneliness.