Assessment of potential cardiotoxic side effects of mitoxantrone in patients with multiple sclerosis

Previous studies showed that mitoxantrone can reduce disability progression in patients with multiple sclerosis (MS). There is, however, concern that it may cause irreversible cardiomyopathy with reduced left ventricular (LV) ejection fraction (EF) and congestive heart failure. The aim of this prospective study was to investigate cardiac side effects of mitoxantrone by repetitive cardiac monitoring in MS patients. The treatment protocol called for ten courses of a combined mitoxantrone (10 mg/m(2) body surface) and methylprednisolone therapy. Before each course, a transthoracic echocardiogram was performed to determine the LV end-diastolic diameter, the end-systolic diameter and the fractional shortening; the LV-EF was calculated. Seventy-three patients participated (32 males; age 48 +/- 12 years, range 20-75 years; 25 with primary progressive, 47 with secondary progressive and 1 with relapsing-remitting MS) who received at least four courses of mitoxantrone. Three of the 73 patients were excluded during the study (2 patients discontinued therapy; 1 patient with a previous history of ischemic heart disease developed atrial fibrillation after the second course of mitoxantrone). The mean cumulative dose of mitoxantrone was 114.0 +/- 33.8 mg. The mean follow-up time was 23.4 months (range 10-57 months). So far, there has been no significant change in any of the determined parameters (end-diastolic diameter, end-systolic diameter, fractional shortening, EF) over time during all follow-up investigations. Mitoxantrone did not cause signs of congestive heart failure in any of the patients. Further cardiac monitoring is, however, needed to determine the safety of mitoxantrone after longer follow-up times and at higher cumulative doses. Copyright (C) 2005 S. Karger AG, Basel

Oligodendrocyte differentiation from adult multipotent stem cells is modulated by glutamate

We used multipotent stem cells (MSCs) derived from the young rat subventricular zone (SVZ) to study the effects of glutamate in oligodendrocyte maturation. Glutamate stimulated oligodendrocyte differentiation from SVZ-derived MSCs through the activation of specific N-methyl--aspartate (NMDA) receptor subunits. The effect of glutamate and NMDA on oligodendrocyte differentiation was evident in both the number of newly generated oligodendrocytes and their morphology. In addition, the levels of NMDAR1 and NMDAR2A protein increased during differentiation, whereas NMDAR2B and NMDAR3 protein levels decreased, suggesting differential expression of NMDA receptor subunits during maturation. Microfluorimetry showed that the activation of NMDA receptors during oligodendrocyte differentiation elevated cytosolic calcium levels and promoted myelination in cocultures with neurons. Moreover, we observed that stimulation of MSCs by NMDA receptors induced the generation of reactive oxygen species (ROS), which were negatively modulated by the NADPH inhibitor apocynin, and that the levels of ROS correlated with the degree of differentiation. Taken together, these findings suggest that ROS generated by NADPH oxidase by the activation of NMDA receptors promotes the maturation of oligodendrocytes and favors myelination

Review of Issues Associated with Safe Operation and Management of the Space Shuttle Program

At the request of the President of the United States through the Office of Science and Technology Policy (OSTP), the NASA Administrator tasked the Aerospace Safety Advisory Panel with the responsibility to identify and review issues associated with the safe operation and management of the Space Shuttle program arising from ongoing efforts to improve and streamline operations. These efforts include the consolidation of operations under a single Space Flight Operations Contract (SFOC), downsizing the Space Shuttle workforce and reducing costs of operations and management. The Panel formed five teams to address the potentially significant safety impacts of the seven specific topic areas listed in the study Terms of Reference. These areas were (in the order in which they are presented in this report): Maintenance of independent safety oversight; implementation plan for the transition of Shuttle program management to the Lead Center; communications among NASA Centers and Headquarters; transition plan for downsizing to anticipated workforce levels; implementation of a phased transition to a prime contractor for operations; Shuttle flight rate for Space Station assembly; and planned safety and performance upgrades for Space Station assembly. The study teams collected information through briefings, interviews, telephone conversations and from reviewing applicable documentation. These inputs were distilled by each team into observations and recommendations which were then reviewed by the entire Panel

Challenges in supporting lay carers of patients at the end of life: results from focus group discussions with primary healthcare providers

Background: Family caregivers (FCGs) of patients at the end of life (EoL) cared for at home receive support from professional and non-professional care providers. Healthcare providers in general practice play an important role as they coordinate care and establish contacts between the parties concerned. To identify potential intervention targets, this study deals with the challenges healthcare providers in general practice face in EoL care situations including patients, caregivers and networks. Methods: Focus group discussions with general practice teams in Germany were conducted to identify barriers to and enablers of an optimal support for family caregivers. Focus group discussions were analysed using content analysis. Results: Nineteen providers from 11 general practices took part in 4 focus group discussions. Participants identified challenges in communication with patients, caregivers and within the professional network. Communication with patients and caregivers focused on non-verbal messages, communicating at an appropriate time and perceiving patient and caregiver as a unit of care. Practice teams perceive themselves as an important part of the healthcare network, but also report difficulties in communication and cooperation with other healthcare providers. Conclusion: Healthcare providers in general practice identified relational challenges in daily primary palliative care with potential implications for EoL care. Communication and collaboration with patients, caregivers and among healthcare providers give opportunities for improving palliative care with a focus on the patient-caregiver dyad. It is insufficient to demand a (professional) support network; existing structures need to be recognized and included into the care

Psychological process from hospitalization to death among uninformed terminal liver cancer patients in Japan

BACKGROUND: Although the attitude among doctors toward disclosing a cancer diagnosis is becoming more positive, informing patients of their disease has not yet become a common practice in Japan. We examined the psychological process, from hospitalization until death, among uninformed terminal cancer patients in Japan, and developed a psychological model. METHODS: Terminal cancer patients hospitalized during the recruiting period voluntarily participated in in-depth interviews. The data were analyzed by grounded theory. RESULTS: Of the 87 uninformed participants at the time of hospitalization, 67% (N = 59) died without being informed of their diagnosis. All were male, 51–66 years of age, and all experienced five psychological stages: anxiety and puzzlement, suspicion and denial, certainty, preparation, and acceptance. At the end of each stage, obvious and severe feelings were observed, which were called "gates." During the final acceptance stage, patients spent a peaceful time with family, even talking about their dreams with family members. CONCLUSION: Unlike in other studies, the uninformed patients in this study accepted death peacefully, with no exceptional cases. Despite several limitations, this study showed that almost 70% of the uninformed terminal cancer patients at hospitalization died without being informed, suggesting an urgent need for culturally specific and effective terminal care services for cancer patients in Japan

National strategy for palliative care of severely ill and dying people and their relatives in pandemics (PallPan) in Germany - study protocol of a mixed-methods project

BACKGROUND In the SARS-CoV-2 pandemic, general and specialist Palliative Care (PC) plays an essential role in health care, contributing to symptom control, psycho-social support, and providing support in complex decision making. Numbers of COVID-19 related deaths have recently increased demanding more palliative care input. Also, the pandemic impacts on palliative care for non-COVID-19 patients. Strategies on the care for seriously ill and dying people in pandemic times are lacking. Therefore, the program 'Palliative care in Pandemics' (PallPan) aims to develop and consent a national pandemic plan for the care of seriously ill and dying adults and their informal carers in pandemics including (a) guidance for generalist and specialist palliative care of patients with and without SARS-CoV-2 infections on the micro, meso and macro level, (b) collection and development of information material for an online platform, and (c) identification of variables and research questions on palliative care in pandemics for the national pandemic cohort network (NAPKON). METHODS Mixed-methods project including ten work packages conducting (online) surveys and qualitative interviews to explore and describe i) experiences and burden of patients (with/without SARS-CoV-2 infection) and their relatives, ii) experiences, challenges and potential solutions of health care professionals, stakeholders and decision makers during the SARS-CoV-2 pandemic. The work package results inform the development of a consensus-based guidance. In addition, best practice examples and relevant literature will be collected and variables for data collection identified. DISCUSSION For a future \textquotedblpandemic preparedness\textquotedbl national and international recommendations and concepts for the~care of severely ill and dying people are necessary considering both generalist and specialist palliative care in the home care and inpatient setting