Underrepresentation of Elderly People in Randomised Controlled Trials. The Example of Trials of 4 Widely Prescribed Drugs

BACKGROUND: We aimed to determine the representation of elderly people in published reports of randomized controlled trials (RCTs). We focused on trials of 4 medications--pioglitazone, rosuvastatin, risedronate, and valsartan-frequently used by elderly patients with chronic medical conditions. METHODS AND FINDINGS: We selected all reports of RCTs indexed in PubMed from 1966 to April 2008 evaluating one of the 4 medications of interest. Estimates of the community-based "on-treatment" population were from a national health insurance database (SNIIR-AM) covering approximately 86% of the population in France. From this database, we evaluated data claims from January 2006 to December 2007 for 1,958,716 patients who received one of the medications of interest for more than 6 months. Of the 155 RCT reports selected, only 3 studies were exclusively of elderly patients (2 assessing valsartan; 1 risedronate). In only 4 of 37 reports (10.8%) for pioglitazone, 4 of 22 (18.2%) for risedronate, 3 of 29 (10.3%) for rosuvastatine and 9 of 67 (13.4%) for valsartan, the proportion of patients aged 65 or older was within or above that treated in clinical practice. In 62.2% of the reports for pioglitazone, 40.9% for risedronate, 37.9% for rosuvastatine, and 70.2% for valsartan, the proportion of patients aged 65 or older was lower than half that in the treated population. The representation of elderly people did not differ by publication date or sample size. CONCLUSIONS: Elderly patients are poorly represented in RCTs of drugs they are likely to receive

Pain in elderly people with severe dementia: A systematic review of behavioural pain assessment tools

BACKGROUND: Pain is a common and major problem among nursing home residents. The prevalence of pain in elderly nursing home people is 40–80%, showing that they are at great risk of experiencing pain. Since assessment of pain is an important step towards the treatment of pain, there is a need for manageable, valid and reliable tools to assess pain in elderly people with dementia. METHODS: This systematic review identifies pain assessment scales for elderly people with severe dementia and evaluates the psychometric properties and clinical utility of these instruments. Relevant publications in English, German, French or Dutch, from 1988 to 2005, were identified by means of an extensive search strategy in Medline, Psychinfo and CINAHL, supplemented by screening citations and references. Quality judgement criteria were formulated and used to evaluate the psychometric aspects of the scales. RESULTS: Twenty-nine publications reporting on behavioural pain assessment instruments were selected for this review. Twelve observational pain assessment scales (DOLOPLUS2; ECPA; ECS; Observational Pain Behavior Tool; CNPI; PACSLAC; PAINAD; PADE; RaPID; Abbey Pain Scale; NOPPAIN; Pain assessment scale for use with cognitively impaired adults) were identified. Findings indicate that most observational scales are under development and show moderate psychometric qualities. CONCLUSION: Based on the psychometric qualities and criteria regarding sensitivity and clinical utility, we conclude that PACSLAC and DOLOPLUS2 are the most appropriate scales currently available. Further research should focus on improving these scales by further testing their validity, reliability and clinical utility

The geriatric minimum data set for clinical trials (GMDS)

Item does not contain fulltextBACKGROUND: To overcome the weak evidence base coming from often poor and insufficient clinical research in older people, a minimum data set to achieve harmonisation is highly advisable. This will lead to uniform nomenclature and to the standardisation of the assessment tools. Our primary objective was to develop a Geriatric Minimum Data Set (GMDS) for clinical research. METHODS: Investigators from 33 leading Research Centres in Europe (selected based on pre-defined criteria), agreed to establish GerontoNet, a network for research collaboration. Following a systematic review of literature performed before the meeting, the expert panel identified 79 functional, cognitive, nutritional and social statements. RESULTS: Of the initial 79 statements, 49 were found appropriate for a GMDS. After an additional stage of evaluation, a 25-item data set was proposed as the minimum set of information to be included in any future clinical trial involving older people. The GMDS covers 7 domains: general information including data on clinical diagnosis and medication use (5 items), functional performance (5 items), cognitive and emotional status (4 items), cardiovascular risk profile (3 items), nutritional status (3 items), biochemical parameters (1 set and 1 item), and social status (3 items). CONCLUSION: The proposed GMDS provides an enhanced opportunity for research in elderly populations with appropriate outcome measures, and would greatly facilitate meta-analysis of relevant clinical trials

Factors Influencing Early Rehabilitation After THA: A Systematic Review

A wide variation exists in rehabilitation after total hip arthroplasty (THA) in part due to a paucity of evidence-based literature. We asked whether a minimally invasive surgical approach, a multimodal approach to pain control with revised anesthesia protocols, hip restrictions, or preoperative physiotherapy achieved a faster rehabilitation and improved immediate short-term outcome. We conducted a systematic review of 16 level I and II studies after a strategy-based search of English literature on OVID Medline, PubMed, CINAHL, Cochrane, and EMBASE databases. We defined the endpoint of assessment as independent ambulation and ability to perform activities of daily living. Literature supports the use of a multimodal pain control to improve patient compliance in accelerated rehabilitation. Multimodal pain control with revised anesthesia protocols and accelerated rehabilitation speeds recovery after minimally invasive THA compared to the standard approach THA, but a smaller incision length or minimally invasive approach does not demonstrably improve the short-term outcome. Available studies justify no hip restrictions following an anterolateral approach but none have examined the question for a posterior approach. Preoperative physiotherapy may facilitate faster postoperative functional recovery but multicenter and well-designed prospective randomized studies with outcome measures are necessary to confirm its efficacy

The multifaceted role of complement in kidney transplantation

Increasing evidence indicates an integral role for the complement system in the deleterious inflammatory reactions that occur during critical phases of the transplantation process, such as brain or cardiac death of the donor, surgical trauma, organ preservation and ischaemia–reperfusion injury, as well as in humoral and cellular immune responses to the allograft. Ischaemia is the most common cause of complement activation in kidney transplantation and in combination with reperfusion is a major cause of inflammation and graft damage. Complement also has a prominent role in antibody-mediated rejection (ABMR) owing to ABO and HLA incompatibility, which leads to devastating damage to the transplanted kidney. Emerging drugs and treatment modalities that inhibit complement activation at various stages in the complement cascade are being developed to ameliorate the damage caused by complement activation in transplantation. These promising new therapies have various potential applications at different stages in the process of transplantation, including inhibiting the destructive effects of ischaemia and/or reperfusion injury, treating ABMR, inducing accommodation and modulating the adaptive immune response