A prospective, randomized, open label, phase iii clinical trial of novottf-100a vs best standard of care chemotherapy in patients with recurrent glioblastoma

BACKGROUND: Glioblastoma, the most common adult primary malignant brain tumor, confers poor prognosis (median survival of 15 months) notwithstanding aggressive treatment. Combination chemotherapy including carmustine (BCNU) or temozolomide (TMZ) with the MGMT inhibitor O6-benzylguanine (O6BG) has been used, but has been associated with dose-limiting hematopoietic toxicity. OBJECTIVE: To assess safety and efficacy of a retroviral vector encoding the O6BG-resistant MGMTP140K gene for transduction and autologous transplantation of hematopoietic stem cells (HSCs) in MGMT unmethylated, newly diagnosed glioblastoma patients in an attempt to chemoprotect bone marrowduring combination O6BG/TMZ therapy. METHODS: Three patients have been enrolled in the first cohort. Patients underwent standard radiation therapy without TMZ followed by G-CSF mobilization, apheresis, and conditioning with 600 mg/m2 BCNU prior to infusion of gene-modified cells. Posttransplant, patients were treated with 28-day cycles of single doseTMZ (472 mg/m2) with 48-hour intravenous O6BG (120 mg/m2 bolus, then 30 mg/m2/d). RESULTS: The BCNU dose was nonmyeloablative with ANC ,500/mL for ≤3 d and nadir thrombocytopenia of 28,000/mL. Gene marking in pre-infusion colony forming units (CFUs) was 70.6%, 79.0%, and 74.0% in Patients 1, 2, and 3, respectively, by CFU-PCR. Following engraftment, gene marking in white blood cells and sorted granulocytes ranged between 0.37-0.84 and 0.33-0.83 provirus copies, respectively, by real-time PCR. Posttransplant gene marking in CFUs from CD34-selected cells ranged from 28.5% to 47.4%. Patients have received 4, 3, and 2 cycles of O6BG/TMZ, respectively, with evidence for selection of gene-modified cells. One patient has received a single dose-escalated cycle at 590 mg/m2 TMZ. No additional extra-hematopoietic toxicity has been observed thus far and all three patients exhibit stable disease at 7-8 months since diagnosis CONCLUSIONS: We believe that these data demonstrate the feasibility of achieving significant engraftment of MGMTP140K-modified cells with a well-tolerated dose of BCNU. Further follow-up will determine whether this approach will allow for further dose escalation of TMZ and improved survival.

Respiratory viruses in the pediatric intensive care unit: prevalence and clinical aspects

A survey was conducted in two pediatric intensive care units in hospitals in Porto Alegre, Brazil, in order to monitor the main respiratory viruses present in bronchiolitis and/or pneumonia and their involvement in the severity of viral respiratory infections. Viral respiratory infection prevalence was 38.7%. In bronchiolitis, respiratory syncytial virus (RSV) was detected in 36% of the cases. In pneumonia, the prevalence rates were similar for adenovirus (10.3%) and RSV (7.7%). There was a difference among the viruses detected in terms of frequency of clinical findings indicating greater severity. Frequency of crackles in patients with RSV (47.3%) showed a borderline significance (p = 0.055, Fisher's exact test) as compared to those with adenovirus (87.5%). The overall case fatality rate in this study was 2.7%, and adenovirus showed a significantly higher case fatality rate (25%) than RSV (2.8%) (p = 0.005). Injected antibiotics were used in 49% of the children with RSV and 60% of those with adenovirus. Adenovirus was not detected in any of the 33 children submitted to oxygen therapy.

Primary medical care in Irish prisons

An industrial dispute between prison doctors and the Irish Prison Service (IPS) took place in 2004. Part of the resolution of that dispute was that an independent review of prison medical and support services be carried out by a University Department of Primary Care. The review took place in 2008 and we report here on the principal findings of that review.   This study utilised a mixed methods approach. An independent expert medical evaluator (one of the authors, DT) inspected the medical facilities, equipment and relevant custodial areas in eleven of the fourteen prisons within the IPS. Semistructured interviews took place with personnel who had operational responsibility for delivery of prison medical care. Prison doctors completed a questionnaire to elicit issues such as allocation of clinician's time, nurse and administrative support and resources available.   There was wide variation in the standard of medical facilities and infrastructure provided across the IPS. The range of medical equipment available was generally below that of the equivalent general practice scheme in the community. There is inequality within the system with regard to the ratio of doctor-contracted time relative to the size of the prison population. There is limited administrative support, with the majority of prisons not having a medical secretary. There are few psychiatric or counselling sessions available.   People in prison have a wide range of medical care needs and there is evidence to suggest that these needs are being met inconsistently in Irish prisons.This resource was contributed by The National Documentation Centre on Drug Use.

Effectiveness of brief alcohol interventions in primary care populations.

Excessive drinking contributes significantly to social problems, physical and psychological illness, injury and death. Hidden effects include increased levels of violence, accidents and suicide. Most alcohol-related harm is caused by excessive drinkers whose consumption exceeds recommended drinking levels, not the drinkers with severe alcohol dependency problems. One way to reduce consumption levels in a community may be to provide a brief intervention in primary care over one to four sessions. This is provided by healthcare workers such as general physicians, nurses or psychologists. In general practice, patients are routinely asked about alcohol consumption during registration, general health checks and as part of health screening (using a questionnaire). They tend not to be seeking help for alcohol problems when presenting. The intervention they are offered includes feedback on alcohol use and harms, identification of high risk situations for drinking and coping strategies, increased motivation and the development of a personal plan to reduce drinking. It takes place within the time-frame of a standard consultation, 5 to 15 minutes for a general physician, longer for a nurse.A total of 29 controlled trials from various countries were identified, in general practice (24 trials) or an emergency setting (five trials). Participants drank an average of 306 grams of alcohol (over 30 standard drinks) per week on entry to the trial. Over 7000 participants with a mean age of 43 years were randomised to receive a brief intervention or a control intervention, including assessment only. After one year or more, people who received the brief intervention drank less alcohol than people in the control group (average difference 38 grams/week, range 23 to 54 grams). For men (some 70% of participants), the benefit of brief intervention was a difference of 57 grams/week, range 25 to 89 grams (six trials). The benefit was not clear for women. The benefits of brief intervention were similar in the normal clinical setting and in research settings with greater resources. Longer counselling had little additional benefit.This resource was contributed by The National Documentation Centre on Drug Use.

The effectiveness of brief alcohol interventions in primary care settings: A systematic review

Numerous studies have reported that brief interventions delivered in primary care are effective in reducing excessive drinking. However, much of this work has been criticised for being clinically unrepresentative. This review aimed to assess the effectiveness of brief interventions in primary care and determine if outcomes differ between efficacy and effectiveness trials. Approach. A pre-specified search strategy was used to search all relevant electronic databases up to 2006. The authors also hand-searched the reference lists of key articles and reviews. They included randomised controlled trials (RCT) involving patients in primary care who were not seeking alcohol treatment and who received brief intervention. Two authors independently abstracted data and assessed trial quality. Random effects meta-analyses, subgroup and sensitivity analyses and meta-regression were conducted.This resource was contributed by The National Documentation Centre on Drug Use.

The functional outcome and recovery of patients admitted to an intensive care unit following drug overdose: a follow-up study.

Patients who have overdosed on drugs commonly present to emergency departments, with only the most severe cases requiring intensive care unit (ICU) admission. Such patients typically survive hospitalisation. We studied their longer term functional outcomes and recovery patterns which have not been well described. All patients admitted to the 18-bed ICU of a university-affiliated teaching hospital following drug overdoses between 1 January 2004 and 31 December 2006 were identified. With ethical approval, we evaluated the functional outcome and recovery patterns of the surviving patients 31 months after presentation, by telephone or personal interview. These were recorded as Glasgow outcome score, Karnofsky performance index and present work status. During the three years studied, 43 patients were identified as being admitted to our ICU because of an overdose. The average age was 34 years, 72% were male and the mean APACHE II score was 16.7. Of these, 32 were discharged from hospital alive. Follow-up data was attained on all of them. At a median of 31 months follow-up, a further eight had died. Of the 24 surviving there were 13 unemployed, seven employed and four in custody. The median Glasgow outcome score of survivors was 4.5, their Karnofsky score 80. Admission to ICU for treatment of overdose is associated with a very high risk of death in both the short- and long-term. While excellent functional recovery is achievable, 16% of survivors were held in custody and 54% unemployed.This resource was contributed by The National Documentation Centre on Drug Use.

An evaluation of the inappropriate prescribing in older residents in long term care facilities in the greater Cork and Northern Ireland regions using the STOPP and Beers' criteria.

This work has highlighted a number of areas of prescribing concern, for example, the long term use of both benzodiazepines and hypnotics, in older residents residing in long term care facilities. Each of these individual areas should be further investigated to determine the underlying reason(s) for the prescribing concerns in these areas and strategic methods of addressing and preventing further issues should be developed on a national level.This resource was contributed by The National Documentation Centre on Drug Use.

Whole-person care: from rhetoric to reality. Achieving parity between mental and physical health.

The report presents evidence on a range of factors affecting disparity between mental and physical health, and includes case studies and examples of good practice to illustrate some of the key issues and solutions. It should be seen as the first stage of an on-going process over the next 5"10 years that will deliver parity for mental health and make whole-person care a reality. It builds on the Implementation Framework for the Mental Health Strategy in providing further analysis of why parity does not currently exist, and the actions required to bring it about. A parity approach should enable NHS and local authority health and social care services to provide a holistic, whole person response to each individual, whatever their needs, and should ensure that all publicly funded services, including those provided by private organisations, give people's mental health equal status to their physical health needs. Central to this approach is the fact that there is a strong relationship between mental health and physical health, and that this influence works in both directions. Poor mental health is associated with a greater risk of physical health problems, and poor physical health is associated with a greater risk of mental health problems. Mental health affects physical health and vice versa. The report makes a series of key recommendations for the UK government, policy-makers and health professionals. Recommendations include: The government and the NHS Commissioning Board should work together to give people equivalent levels of access to treatment for mental health problems as for physical health problems, agreed standards for waiting times, and agreed standards for emergency/crisis mental healthcare. Action to promote good mental health and to address mental health problems needs to start at the earliest stage of a person's life and continue throughout the life course. Preventing premature mortality " there must be a major focus on improving the physical health of people with mental health problems. Public health programmes must include a focus on the mental health dimension of issues commonly considered as physical health concerns, such as smoking, obesity and substance misuse. Commissioners need to regard liaison doctors (who work across physical and mental healthcare) as an absolute necessity rather than an optional luxury. NHS and social care commissioners should commission liaison psychiatry and liaison physician services to drive a whole-person, integrated approach to healthcare in acute, secure, primary care and community settings, for all ages. Mental health services and mental health research must receive funding that reflects the prevalence of mental health problems and their cost to society. Mental illness is responsible for the largest proportion of the disease burden in the UK (22.8%), larger than that of cardiovascular disease (16.2%) or cancer (15.9%). However, only 11% of the NHS budget was spent on NHS services to treat mental health problems for all ages during 2010/11. Culture, attitudes and stigma " zero-tolerance policies in relation to discriminatory attitudes or behaviours should be introduced in all health settings to help combat the stigma that is still attached to mental illness within medicine. Political and managerial leadership is required at all levels. There should be a mechanism at national level for driving a parity approach to relevant policy areas across government; all local councils should have a lead councillor for mental health; all providers of specialist mental health services should have a board-level lead for physical health and all providers of physical healthcare services should have a board-level lead for mental health. The General Medical Council (GMC) and Nursing and Midwifery Council (NMC) should consider how medical and nursing study and training could give greater emphasis to mental health. Mental and physical health should be integrated within undergraduate medical education.This resource was contributed by The National Documentation Centre on Drug Use.

Guidelines for the management of depression and anxiety disorders in primary care.

High risk groups for depression and anxiety disorders include those with co-occuring alcohol or other drug misuse.This resource was contributed by The National Documentation Centre on Drug Use.

Introduction to Basic Health Care Statistics

A video summary by Catherine Comiskey

Elder Care Meals on Wheels

Elder Care Meals on Wheels provides a nutritious meal to older members of the community. Local Development Companies, The Local Authority, FAS Initiative Type Meals on Wheels Location Tipperary Target Groups Older people Funding Local Development Companies, The Local Authority, FAS Partner Agencies FÁS Local Authority Local Development COmpany

A framework for quality in long-term residential care for older people in Ireland / National Council on Ageing and Older People

In 1999 the National Council on Ageing and Older People commissioned a postal survey of all long-term residential care facilities in the country to determie: - whether facilities had quality initiatives in operation - providers' views and aspirations for future provision of long-term care - providers' views on the introduction of a national quality monitoring policy This report is the outcome of the programme of work conducted by the Council on the quality of long-term residential care provision for older people in Ireland. The aim of the report is to provide a framework for developing quality in long-term residential care settings with a focus on the well-being, dignity and autonomy of older residents.

Palliative Care - A Five Year/Medium Term Development Framework

This document details the HSE's Palliative Care Services - Five Year Medium Term Development Framework (2009 - 2013). It has been developed using a holistic, system-wide, approach to addressing the level of need identified by both the Baseline Study on the Provision of Hospice / Specialist Palliative Care Services in Ireland (2006) as well as the HSE Audit of Palliative Care Service Provision (2007). The HSE Audit was conducted by each of the four HSE Administrative Areas, in conjunction with Area Development Committees, against the recommendations of the Report of the National Advisory Committee on Palliative Care 2001 (the NACPC Report). Therefore, this document is grounded in the recommendations of the NACPC Report, (e.g. palliative care definition, palliative care service areas, staffing and bed number ratios), and informed by the findings of the HSE Audit. The purpose of this document is not to replace the recommendations of the NACPC Report from a policy context, nor does it represent a new national strategy for palliative care. This document details the required actions and initiatives necessary to address the gaps in palliative care service provision, against the recommendations set out in the NACPC Report.

Five year prognosis in patients with angina identified in primary care: incident cohort study

The objective of this study was to ascertain the risk of acute myocardial infarction, invasive cardiac procedures, and mortality among patients with newly diagnosed angina over five years. This is an Incident cohort study of patients with primary care data linked to secondary care and mortality data. 40 primary care practices in Scotland participated. Participants 1785 patients with a diagnosis of angina as their first manifestation of ischaemic heart disease were monitored between1 January 1998 to 31 December 2001.