Older adult participation in cancer clinical trials: A systematic review of barriers and interventions

Cancer is a disease of aging and, as the world's population ages, the number of older persons with cancer is increasing and will make up a growing share of the oncology population in virtually every country. Despite this, older patients remain vastly underrepresented in research that sets the standards for cancer treatments. Consequently, most of what we know about cancer therapeutics is based on clinical trials conducted in younger, healthier patients, and effective strategies to improve clinical trial participation of older adults with cancer remain sparse. For this systematic review, the authors evaluated published studies regarding barriers to participation and interventions to improve participation of older adults in cancer trials. The quality of the available evidence was low and, despite a literature describing multifaceted barriers, only one intervention study aimed to increase enrollment of older adults in trials. The findings starkly amplify the paucity of evidence-based, effective strategies to improve participation of this underrepresented population in cancer trials. Within these limitations, the authors provide their opinion on how the current cancer research infrastructure must be modified to accommodate the needs of older patients. Several underused solutions are offered to expand clinical trials to include older adults with cancer. However, as currently constructed, these recommendations alone will not solve the evidence gap in geriatric oncology, and efforts are needed to meet older and frail adults where they are by expanding clinical trials designed specifically for this population and leveraging real-world data.     

Assessing cumulative health risks from exposure to environmental mixtures - three fundamental questions

Differential exposure to mixtures of environmental agents, including biological, chemical, physical, and psychosocial stressors, can contribute to increased vulnerability of human populations and ecologic systems. Cumulative risk assessment is a tool for organizing and analyzing information to evaluate the probability and seriousness of harmful effects caused by either simultaneous and/or sequential exposure to multiple environmental stressors. In this article we focus on elucidating key challenges that must be addressed to determine whether and to what degree differential exposure to environmental mixtures contributes to increased vulnerability of exposed populations. In particular, the emphasis is on examining three fundamental and interrelated questions that must be addressed as part of the process to assess cumulative risk: a) Which mixtures are most important from a public health perspective? and b) What is the nature (i.e., duration, frequency, timing) and magnitude (i.e., exposure concentration and dose) of relevant cumulative exposures for the population of interest? c) What is the mechanism (e.g., toxicokinetic or toxicodynamic) and consequence (e.g., additive, less than additive, more than additive) of the mixture's interactive effects on exposed populations? The focus is primarily on human health effects from chemical mixtures, and the goal is to reinforce the need for improved assessment of cumulative exposure and better understanding of the biological mechanisms that determine toxicologic interactions among mixture constituents.     

Facilitating good process in primary palliative care: does the Gold Standards Framework enable quality performance?

BACKGROUND: Palliative care is an important, complex aspect of primary care, requiring a multidisciplinary approach. The Gold Standards Framework (GSF), a programme used by over 3,000 UK practices, aims to facilitate high-quality palliative care through the introduction of systematic clinical and organizational processes. Quality payments for palliative care are available to UK practices which maintain registers and hold multidisciplinary meetings. OBJECTIVES: To explore the effectiveness and sustainability of the implementation of GSF at practice level. METHODS: The study followed a qualitative comparative case study design using in-depth interviews and observational data with 15 practices participating in GSF, from three areas differing in socio-geography. Semi-structured interviews (total 45) with GPs, community nurses and practice managers were supplemented by observation of practice meetings and systems, to provide contextual insights. Transcribed interviews were analysed using a thematic matrix approach and comparisons were made within and between practices. Practices were identified on a continuum of performance (high, medium and minimal) according to the evidence of functioning in palliative care-related activity. RESULTS: Considerable variation existed between practices in both the extent of palliative care-related processes and the effectiveness of inter-professional communication. High-performing practices displayed a clear-shared purpose for palliative care with effective communication, whereas minimal performing practices demonstrated little utilization of basic GSF processes and deficiencies in inter-professional communication. CONCLUSION: Effective palliative care requires good team relationships and robust processes. While GSF can enable such improvements, quality measures focusing on processes alone are inadequate to distinguish good practice, questioning the effectiveness of current quality measures in UK general practice.     

Venezuelan equine encephalitis virus vaccine candidate (V3526) safety, immunogenicity and efficacy in horses

A new vaccine, V3526, is a live-attenuated virus derived by site-directed mutagenesis from a virulent clone of the Venezuelan equine encephalitis virus (VEEV) IA/B Trinidad donkey (TrD) strain, intended for human use in protection against Venezuelan equine encephalitis (VEE). Two studies were conducted in horses to evaluate the safety, immunogenicity, ability to boost and protective efficacy of V3526 against challenges of TrD and VEEV IE 64A99. Horses were vaccinated subcutaneously (SC) with 10(7), 10(5), 10(3) or 10(2) plaque-forming units (pfu) of V3526. Control horses were sham immunized. In the first study, challenge viruses (TrD or 64A99) were administered SC 28 days post-vaccination (PV). No viremia and only mild fluctuation in white blood cell counts were observed PV. None of the V3526 vaccinated horses showed clinical signs of disease or pathology of VEE post-challenge (PC). In contrast, control horses challenged SC with 10(4)pfu TrD became viremic and showed classical signs of VEE beginning on Day 3 PC, including elevated body temperature, anorexia, leukopenia and malaise. Moderate to severe encephalitis was found in three of five control horses challenged with TrD. Control horses challenged with 64A99 failed to develop detectable viremia, but did exhibit a brief febrile episode at 1-3 days PC. None of the 10 immunized horses challenged with 64A99 became pyrexic. Twenty four of 25 horses immunized with V3526 in the first study developed serum neutralizing antibody to TrD and 64A99 within 14 days PV. Vaccinations with V3526, at doses as low as 10(2)pfu, were safe and efficacious in protecting horses against a virulent TrD virus challenge. The second study supported that repeat dosing resulted in an increase in serum neutralizing antibody to TrD.     

Private demand for cholera vaccines in Beira, Mozambique

In the summer of 2005, we interviewed 996 randomly selected respondents in Beira, Mozambique concerning their willingness and ability to pay for cholera vaccine for themselves and for other household members. Respondents were told that two doses of the vaccine would be required 2 weeks apart, and that the cholera vaccine would offer excellent protection against infection for the first year following vaccination, and some protection during the second and third year after a person is vaccinated. This research was carried out in order to learn more about private demand for vaccines in a cholera-endemic area. We asked two types of valuation questions: (1) a discrete-price offer for a vaccine that could be purchased for household members and (2) a payment card designed to assess uncertainty in the respondent's demand for a vaccine for self-protection. We estimate average household willingness to pay (WTP) for cholera vaccines in Beira to be 2005 US$ 8.45. This estimate of household WTP represents the perceived private economic benefits to a household--six persons on average--of giving all members free cholera vaccines.     

Nucleic acid-based antiviral drugs against seasonal and avian influenza viruses

Influenza viruses are etiological agents of deadly flu that continue to pose global health threats, and have caused global pandemics that killed millions of people worldwide. The availability of neuraminidase inhibitors and attenuated vaccines improves our ability to defend against influenza, but their benefits can be significantly limited by drug-resistance and virus mutations. Nucleic acid-based drugs may represent a promising class of antiviral agents that could play a role in the prevention and treatment of influenza. Efficacy studies in animals have shown that ds RNA, such as poly ICLC can provide effective and broad-spectrum prophylaxis against lethal challenges against various strains of influenza A virus. Furthermore, similar level of antiviral protection in mice can be provided by using short fragments of oligonucleotides that induce antiviral immunity. Finally, influenza virus expression can also be specifically inhibited or suppressed using antisense oligonucleotides that bind to viral mRNA encoding key viral proteins. The versatility and potency of nucleic acid-based drugs make them potential drug candidates for used in seasonal or pandemic influenza situations.     

Geriatrics and physical medicine and rehabilitation: common principles,complementary approaches,and 21st century demographics

The demographic changes occurring in the United States transcend the capabilities of any specific medical specialty to provide optimum care for the elderly. This commentary discusses a statement of principles drafted by representatives of the American Academy of Physical Medicine and Rehabilitation who collaborated with members of 9 other medical and surgical specialties. In this commentary, we argue that geriatrics and physical medicine and rehabilitation (PM&R) share common principles and complementary approaches. We urge physiatrists and other rehabilitation professionals to address the needs of elderly patients and recommend that these principles be incorporated into PM&R practice.