Survival analysis and microarray profiling identify Cd40 as a candidate for the Salmonella susceptibility locus, Ity5.

The outcome of infection with Salmonella Typhimurium in mouse models of human typhoid fever is dependent upon a coordinated complex immune response. A panel of recombinant congenic strains (RCS) derived from reciprocal backcross of A/J and C57BL/6J mice was screened for their susceptibility to Salmonella infection and two susceptibility loci, Ity4 (Immunity to Typhimurium locus 4) and Ity5, were identified. We validated Ity5 in a genetic environment free of the impact of Ity4 using a cross between A/J and 129S6. Using a time-series analysis of genome-wide transcription during infection, comparing A/J with AcB60 mice having a C57BL/6J-derived Ity5 interval, we have identified the differential expression of the positional candidate gene Cd40, Cd40-associated signaling pathways, and the differential expression of numerous genes expressed in neutrophils. CD40 is known to coordinate T cell-dependent B-cell responses and myeloid cell activation. In fact, CD40 signaling is altered in A/J mice as seen by impaired IgM upregulation during infection, decreased Ig class switching, neutropenia, reduced granulocyte recruitment in response to infection and inflammation, and decreased ERK1/2 activity. These results suggest that altered CD40 signaling and granulocyte recruitment in response to infection are responsible for the Ity5-associated Salmonella susceptibility of A/J mice.

Contribution of increased ISG15, ISGylation and deregulated type I IFN signaling in Usp18 mutant mice during the course of bacterial infections.

Host genetics has a key role in susceptibility to Salmonella Typhimurium infection. We previously used N-ethyl-N-nitrosourea (ENU) mutagenesis to identify a loss-of-function mutation within the gene ubiquitin-specific peptidase 18 (Usp18(Ity9)), which confers increased susceptibility to Salmonella Typhimurium. USP18 functions to regulate type I interferon (IFN) signaling and as a protease to remove ISG15 from substrate proteins. Usp18(Ity9) mice are susceptible to infection with Salmonella Typhimurium and have increased expression and function of ISG15, but Usp18(Ity9) mice lacking Isg15 do not show improved survival with Salmonella challenge. Type I IFN signaling is increased in Usp18(Ity9) mice and inhibition of type I IFN signaling is associated with improved survival in mutant mice. Hyperactivation of type I IFN signaling leads to increased IL-10, deregulated expression of autophagy markers and elevated interleukin (IL)-1ß and IL-17. Furthermore, Usp18(Ity9) mice are more susceptible to infection with Mycobacterium tuberculosis, have increased bacterial load in the lung and spleen, elevated inflammatory cytokines and more severe lung pathology. These findings demonstrate that regulation of type I IFN signaling is the predominant mechanism affecting the susceptibility of Usp18(Ity9) mice to Salmonella infection and that hyperactivation of signaling leads to increased IL-10, deregulation of autophagic markers and increased proinflammatory cytokine production.

Impact of Usp18 and IFN signaling in Salmonella-induced typhlitis.

In humans, Salmonella infection causes two major clinical diseases, typhoid fever and a self-limiting gastro-enteritidis. Salmonella transmission occurs by the fecal-oral route and the interactions between the bacteria and the digestive tract epithelium are central to the outcome of the infection. Using a mouse model of typhoid fever, we previously identified a mutation in USP18 affecting type I interferon (IFN) signaling resulting in increased susceptibility to systemic Salmonella infection. In this study, we demonstrate the effects of this mutation during the early response to Salmonella using a model of typhlitis. Mutant Usp18 mice showed a minimal inflammatory response early after Salmonella Typhimurium infection that was associated with low pathologic scores and low IFN-γ production. This resulted in an increased interaction of Salmonella with the cecal epithelium and earlier systemic dissemination of the bacteria. The global transcriptional signature in the cecum of mouse during Salmonella infection showed normal expression of tissue specific genes and upregulation of type I IFN pathway in mutant mice. In control mice, there was a significant over-representation of genes involved in cellular recruitment and antibacterial activity paralleling the histopathological features. These results show the impact of USP18 in the development of Salmonella-induced typhlitis.

Patient-reported outcomes. How important are they?

Outcome after surgical treatment has been based predominantly on objective criteria (biomedical model) and has largely ignored, until recently, the expectations, personal feelings, satisfaction, and quality of life of patients (outcomes model). The importance of this derives from considerations that the viewpoints and priorities of patients may not be the same as those of their surgeons. Furthermore, there is often little correlation between symptom severity and disease severity. Measures of quality of life and patient satisfaction are, thus, important in valid assessment of the results of surgical treatment. Global assessment based on both the biomedical and outcomes models constitutes the ideal. Questionnaires designed to measure both quality life (generic and specific) and patient satisfaction with treatment require careful development and validation by appropriate studies.

Is stroke unit care portable? A systematic review of the clinical trials.

BACKGROUND: It is not known if mobile stroke teams can achieve the good results seen in trials of geographically discrete stroke wards (stroke units). OBJECTIVE: To establish the effectiveness of mobile stroke teams. DESIGN: Systematic review of controlled clinical trials that compared peripatetic systems of organised stroke care (stroke team care) with alternative hospital services. METHODS: Systematic review and meta-analysis (using Cochrane Collaboration methodology and involving the primary trialists). Clinical outcomes included death, dependency, the need for institutional care and measures of the process of care such as the delivery of key investigations and treatments. RESULTS: Six clinical trials (1,085 patients) were identified; five (781 patients) compared some form of stroke team care with conventional care in general medical wards and one (304 patients) compared team care with a comprehensive stroke unit. Compared with care in general wards, stroke team care improved some aspects of the process of care, but clinical outcomes were similar. Compared with a comprehensive stroke unit, stroke team patients were significantly less likely to survive (P <0.001), return home (P < 0.001) or regain independence (P < 0.0001). Most aspects of the process of care were also poorer than in the stroke unit. CONCLUSIONS: Care from a mobile stroke team had no major impact on death, dependency or the need for institutional care.

The impact of physical therapy on functional outcomes after stroke: what's the evidence?

OBJECTIVE: To determine the evidence for physical therapy interventions aimed at improving functional outcome after stroke. METHODS: MEDLINE, CINAHL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, DARE, PEDro, EMBASE and DocOnline were searched for controlled studies. Physical therapy was divided into 10 intervention categories, which were analysed separately. If statistical pooling (weighted summary effect sizes) was not possible due to lack of comparability between interventions, patient characteristics and measures of outcome, a best-research synthesis was performed. This best-research synthesis was based on methodological quality (PEDro score). RESULTS: In total, 151 studies were included in this systematic review; 123 were randomized controlled trials (RCTs) and 28 controlled clinical trials (CCTs). Methodological quality of all RCTs had a median of 5 points on the 10-point PEDro scale (range 2-8 points). Based on high-quality RCTs strong evidence was found in favour of task-oriented exercise training to restore balance and gait, and for strengthening the lower paretic limb. Summary effect sizes (SES) for functional outcomes ranged from 0.13 (95% Cl 0.03-0.23) for effects of high intensity of exercise training to 0.92 (95% Cl 0.54-1.29) for improving symmetry when moving from sitting to standing. Strong evidence was also found for therapies that were focused on functional training of the upper limb such as constraint-induced movement therapy (SES 0.46; 95% Cl 0.07-0.91), treadmill training with or without body weight support, respectively 0.70 (95% Cl 0.29-1.10) and 1.09 (95% Cl 0.56-1.61), aerobics (SES 0.39; 95% Cl 0.05-0.74), external auditory rhythms during gait (SES 0.91; 95% Cl 0.40-1.42) and neuromuscular stimulation for glenohumeral subluxation (SES 1.41; 95% Cl 0.76-2.06). No or insufficient evidence in terms of functional outcome was found for: traditional neurological treatment approaches; exercises for the upper limb; biofeedback; functional and neuromuscular electrical stimulation aimed at improving dexterity or gait performance; orthotics and assistive devices; and physical therapy interventions for reducing hemiplegic shoulder pain and hand oedema. CONCLUSIONS: This review showed small to large effect sizes for task-oriented exercise training, in particular when applied intensively and early after stroke onset. In almost all high-quality RCTs, effects were mainly restricted to tasks directly trained in the exercise programme.

A task-orientated intervention enhances walking distance and speed in the first year post stroke: a randomized controlled trial.

OBJECTIVE: To evaluate the efficacy of a task-orientated intervention in enhancing competence in walking in people with stroke. DESIGN: Two-centre observer-blinded stratified block-randomized controlled trial. SETTING: General community. SUBJECTS: Between May 2000 and February 2003, 91 individuals with a residual walking deficit within one year of a first or recurrent stroke consented to participate. INTERVENTIONS: The experimental intervention comprised 10 functional tasks designed to strengthen the lower extremities and enhance walking balance, speed and distance. The control intervention involved the practice of upper extremity activities. Subjects in both groups attended sessions three times a week for six weeks. MAIN MEASURES: Six-minute walk test (SMWT), 5-m walk (comfortable and maximum pace), Berg Balance Scale, timed 'up and go'. RESULTS: At baseline, subjects in the experimental (n = 44) and control (n = 47) groups walked an average distance of 209 m (SD = 126) and 204 m (SD =131), respectively, on the SMWT. Mean improvements of 40 m (SD =72), and 5 m (SD =66) were observed following the experimental and control interventions, respectively. The between-group difference was 35 m (95% confidence interval (CI) 7, 64). Significant between-group effects of 0.21 m/s (95% CI 0.12, 0.30) and of 0.11 m/s (95% CI 0.03, 0.19) in maximum and comfortable walking speed, respectively, were observed. People with a mild, moderate or severe walking deficit at baseline improved an average of 36 (SD =96), 55 (SD = 56) and 18 m (SD = 23), respectively, in SMWT performance following the experimental intervention. CONCLUSIONS: Study findings support the efficacy of a task-orientated intervention in enhancing walking distance and speed in the first year post stroke, particularly in people with moderate walking deficits.

Evaluation of quality of life after laparoscopic surgery: evidence-based guidelines of the European Association for Endoscopic Surgery.

BACKGROUND: Measuring health-related quality of life (QoL) after surgery is essential for decision making by patients, surgeons, and payers. The aim of this consensus conference was twofold. First, it was to determine for which diseases endoscopic surgery results in better postoperative QoL than open surgery. Second, it was to recommend QoL instruments for clinical research. METHODS: An expert panel selected 12 conditions in which QoL and endoscopic surgery are important. For each condition, studies comparing endoscopic and open surgery in terms of QoL were identified. The expert panel reached consensus on the relative benefits of endoscopic surgery and recommended generic and disease-specific QoL instruments for use in clinical research. RESULTS: Randomized trials indicate that QoL improves earlier after endoscopic than open surgery for gastroesophageal reflux disease (GERD), cholecystolithiasis, colorectal cancer, inguinal hernia, obesity (gastric bypass), and uterine disorders that require hysterectomy. For spleen, prostate, malignant kidney, benign colorectal, and benign non-GERD esophageal diseases, evidence from nonrandomized trials supports the use of laparoscopic surgery. However, many studies failed to collect long-term results, used nonvalidated questionnaires, or measured QoL components only incompletely. The following QoL instruments can be recommended: for benign esophageal and gallbladder disease, the GIQLI or the QOLRAD together with SF-36 or the PGWB; for obesity surgery, the IWQOL-Lite with the SF-36; for colorectal cancer, the FACT-C or the EORTC QLQ-C30/CR38; for inguinal and renal surgery, the VAS for pain with the SF-36 (or the EORTC QLQ-C30 in case of malignancy); and after hysterectomy, the SF-36 together with an evaluation of urinary and sexual function. CONCLUSIONS: Laparoscopic surgery provides better postoperative QoL in many clinical situations. Researchers would improve the quality of future studies by using validated QoL instruments such as those recommended here.

Quality of life after multiple trauma. Aim and scope of the conference.

From September 29 until October 2, 1999, a group of international experts met in Wermelskirchen, Germany, for a consensus conference on "Quality of Life after Multiple Trauma". The meeting was initiated and sponsored by the German Ministry of Education and Research. It was the aim of the group to develop evidence-based guidelines for the systematic evaluation and application of Quality of Life (QoL) measures in patients with severe trauma. The present paper describes the format of the meeting, the selection of the participants, the time schedule, and the proceeding, in order to facilitate the interpretation of the results. The work was structured according to the different types of injury: traumatic brain injury (TBI), multiple injuries without TBI, spinal cord injury, and children with TBI. For each injury group, a specific task force group with 9-13 members was established, consisting of methodologists as well as clinicians from different disciplines. The conference was organised as an alternate sequence of plenary sessions and small working group meetings. The work itself was structured according to the following five questions which have been agreed on and distributed to the participants in advance: 1. What is the major problem (ranking) of the patient at different time points after the accident? 2. Which domains of QoL are affected in the sequelae of trauma? 3. Which instruments are useful to evaluate QoL in trauma patients? 4. Which studies have assessed QoL aspects with which instruments? 5. What instruments should be used in which patient group at what time? The moderators of each task force group summarised the respective results and tried to give recommendations for future application of QoL assessment in trauma patients. As far as possible, the statements should be based on the existing evidence. Furthermore, the groups should recommend QoL measures for use across different patient groups and time points.

Quality of life in patients with spinal cord injury--basic issues, assessment, and recommendations.

INTRODUCTION: Spinal cord injury (SCI) often causes severe disabilities. The degree of functional impairment strongly depends on the level and completeness of lesion (tetraplegic, paraplegic). But evaluation of outcomes also needs to consider the broader concept of health-related quality of the life (HRQL) for SCI patients. A multinational group of clinicians and researchers assessed this concept and reviewed the available instruments for measurement of quality of life in this group of patients. TIME POINTS: Phase I is in the acute clinic; phase II during rehabilitation; phase III after discharge home. Annual follow-up investigations should be maintained. The phase of initial care (phase 0) is important for prognosis and should, therefore, be part of the documentation. INSTRUMENTS: Criteria used to evaluate current QoL measures: reliability, validity, responsiveness, availability of translations, application in SCI patients, existing population norms. Several specific instruments or subscales exist for the following domains: physical and psychological functioning, pain, and handicap. Well-known generic measures of HRQL also have been applied to SCI patients, and a disease-specific instrument has been developed (SCIQL-23). A variety of subjective quality of life measures were evaluated as well. GROUP CONSENSUS/GUIDELINE: Prior to discharge from rehabilitation, the group suggested the use of the Functional Independence Measure, the Hospital Anxiety and Depression Scale and a Visual Analogue Scale for pain. Following discharge from the acute clinic, the SF-36, the Craig Handicap Assessment and Reporting Technique, the Quality of Well-being Scale, or the Life Satisfaction questionnaire were proposed. However, the evidence supporting the use of these instruments is sparse.

Quality of life after multiple trauma--summary and recommendations of the consensus conference.

In October 1999, an international and interdisciplinary consensus conference was held about the assessment and application of quality of life (QoL) measures after multiple trauma. Four working groups represented the following patients: children with traumatic brain injury (TBI); adults with TBI, adults with multiple injuries (but without TBI), and adults with spinal cord injury. According to predefined questions, the groups tried to identify the relevant problems of the patients, at different time points after the traumatic event. A review of the existing instruments for quality of life assessment and the evidence of their application in trauma patients in the scientific literature was performed by each group. Based on the results of these literature reviews it was concluded that there are not enough data to establish "evidence-based" guidelines for QoL assessments in these patients. Nevertheless, the groups comprised of experts clinicians and methodologists, agreed on the Glasgow Outcome Scale and the SF-36 as generic tools for QoL assessment across all trauma patients. It was further recommended to use these generic tools in combination with condition-specific instruments to better reflect the specific problems of the patients. Finally, the whole group suggested that it was not appropriate to view this conference as a "final report" about QoL assessment in trauma patients, but rather it should be seen as a starting point for increased efforts to initiate clinical research projects using QoL as an outcome, to develop better instruments, and to include QoL assessments into daily routines.

Implication of alpha4 phosphoprotein and the rapamycin-sensitive mammalian target-of-rapamycin pathway in prolactin receptor signalling.

A prolactin (PRL)-responsive 3'-end cDNA encoding rat alpha4 phosphoprotein was previously isolated from a rat lymphoma cDNA library. Rat alpha4 is a homologue of yeast Tap42 and is a component of the mammalian target-of-rapamycin (mTOR) signalling pathway that stimulates translation initiation and G1 progression in response to nutrients and growth factors. In the present study, the full-length rat alpha4 cDNA was obtained by 5'-RACE and the 1023 bp open reading frame predicted a 340 amino acid protein of 39.1 kDa. The alpha4 mRNA was expressed in quiescent PRL-dependent Nb2 lymphoma cells deprived of PRL for up to 72 h but expression was downregulated within 4 h of PRL treatment. In contrast, PRL-independent Nb2-Sp cells showed constitutive expression of alpha4 that was not affected by PRL. Western analysis of Nb2 cell lysates or of V5-tagged-alpha4 expressed in COS-1 cells detected a single immunoreactive band of approximately 45 kDa. Enzymatic deglycosylation of affinity-purified 45 kDa alpha4 yielded the predicted 39 kDa protein. Phosphorylation of Nb2 alpha4 was induced by PRL or 2-O-tetradecanoyl-phorbol-13-acetate (TPA) and further enhanced by a combination of PRL and TPA. The Nb2 alpha4 associated with the catalytic subunit of protein phosphatase 2A and localized predominantly in Nb2 nuclear fractions with trace amounts in the cytosol. The immunosuppressant drug rapamycin inhibited proliferation of Nb2 cells in response to PRL or interleukin-2, but had no effect on Nb2-Sp cells. Furthermore, transient overexpression of alpha4 in COS-1 cells inhibited PRL stimulation of the immediate-early gene interferon regulatory factor-1 promoter activity. Therefore, PRL downregulation of alpha4 expression and/or PRL-inducible phosphorylation of alpha4 may be necessary for PRL receptor (PRLr) signalling to the interferon regulatory factor-1 promoter in the Nb2 cells and, furthermore, implicates cross-talk between the mTOR and PRLr signalling cascades during Nb2 cell mitogenesis.

Ozone predictions in Atlanta, Georgia: analysis of the 1999 ozone season.

Ozone prediction has become an important activity in many U.S. ozone nonattainment areas. In this study, we describe the ozone prediction program in the Atlanta metropolitan area and analyze the performance of this program during the 1999 ozone-forecasting season. From May to September, a team of 10 air quality regulators, meteorologists, and atmospheric scientists made a daily prediction of the next-day maximum 8-hr average ozone concentration. The daily forecast was made aided by two linear regression models, a 3-dimensional air quality model, and the no-skill ozone persistence model. The team's performance is compared with the numerical models using several numerical indicators. Our analysis indicated that (1) the team correctly predicted next-day peak ozone concentrations 84% of the time, (2) the two linear regression models had a better performance than a 3-dimensional air quality model, (3) persistence was a strong predictor of ozone concentrations with a performance of 78%, and (4) about half of the team's wrong predictions could be prevented with improved meteorological predictions.

Assessment of back-related quality of life: the continuing challenge.

It is always gratifying to be acknowledged by a colleague and asked to give a talk in a faraway land about a topic of one's particular interest. To be invited, however, to give the Harry Farfan Presidential Lecture at the 27th Meeting of the International Society for the Study of the Lumbar Spine is, for me, a special honor and privilege. Too many years ago, when I was a very junior faculty member at the School of Physical and Occupational Therapy at McGill University in Montreal, Canada, we offered our students a course in Orthopedic Conditions. This course was primarily taught by orthopedic surgeons, rheumatologists, and other members of the medical profession with special interest in disorders of the musculoskeletal system. Teaching in this course was considered to be a professional obligation at McGill, and, while most individuals accepted the invitation, they did so with varying degrees of enthusiasm. Each year, Dr. Harry Farfan graciously agreed and provided several lectures for our students. He told them about the surgical management of problems of the lumbar spine and the necessity of treating the "whole" patient, as well as about his theory as to the cause of low back pain. At that point in time, we were not talking about quality of life as an outcome of care for our patients, but I cannot help but believe that he would keenly approve of the subject of this presentation.

Reliability of the gross motor function measure for children with osteogenesis imperfecta.

PURPOSE: The Gross Motor Function Measure (GMFM) is a criterion-referenced evaluative measure designed to detect change over time for children diagnosed with cerebral palsy (CP). Reliability of this measure has not been tested for children with osteogenesis imperfecta (OI). The purpose of this study was to determine the intra- and interrater reliabilities of the GMFM for use with children diagnosed with OI. METHOD: One physical therapist administered and scored the GMFM for 19 children with OI who were followed at the Shriners Hospital for Children. The assessments were videotaped, then viewed and scored by five physical therapists, including the author, at least six weeks later. Intra- and interrater reliabilities were assessed using intraclass correlation coefficients (ICCs). Kappa statistics were calculated for items demonstrating more disagreement than the majority. RESULTS: The ICCs for intrarater reliability of the five dimensions and total score were 0.99. The ICCs for interrater reliability were 0.98 for the lying and rolling dimension and 0.99 for the other dimensions and total score. Kappa statistics for items demonstrating more disagreement than the majority ranged from 0.552 to 1.00. CONCLUSIONS: This study provides evidence of the reliability of the GMFM for children with OI when scored by pediatric physical therapists familiar with the measure. The videotape provided a consistent situation because each therapist did not directly interact with each child, but rather rated a videotaped session of the child's performance.

Inferring quality of life from performance-based assessments.

PURPOSE: Performance based measures have been suggested as an approach to estimate quality of life, but the associations have not been extensively evaluated. This study's purpose was to determine the associations between quality of life and performance based assessments of disablements in community dwelling individuals post-stroke. METHODS: Forty five people were evaluated in a cross-sectional pilot study. The subjects' quality of life (SF-36), ability in basic and instrumental activities of daily living (ADL), manual dexterity, mobility, neurological impairment, and perception of lateral neglect were evaluated. Multiple regression was employed to find the strongest associations. RESULTS: Neurological impairment explained 34% of the variation in the women's physical health summary score (PCS) of the SF-36. Instrumental ADL and neurological impairment together explained 66% of the women's mental health summary score (MCS) of the SF-36. Manual dexterity of the hemiplegic hand explained 39% of the variation in the men's PCS. CONCLUSION: Performance based measures may be useful to estimate quality of life in non-communicative individuals.

There's no place like home : an evaluation of early supported discharge for stroke.

BACKGROUND AND PURPOSE: Because stroke management is aimed at facilitating community reintegration, it would be logical that the sooner the patient can be discharged home, the sooner reintegration can commence. The purpose of this study was to determine the effectiveness of prompt discharge combined with home rehabilitation on function, community reintegration, and health-related quality of life during the first 3 months after stroke. METHODS: A randomized trial was carried out involving patients who required rehabilitation services and who had a caregiver at home. When medically ready for discharge, persons with stroke were randomized to either the home intervention group (n=58) or the usual care group (n=56). The home group received a 4-week, tailor-made home program of rehabilitation and nursing services; persons randomized to the usual care group received services provided through a variety of mechanisms, depending on institutional, care provider, and personal preference. The main outcome measure was the Physical Health component of the Measuring Outcomes Study Short-Form-36 (SF-36). Associated outcomes measures included the Timed Up & Go (TUG), Barthel Index (BI), the Older Americans Resource Scale for instrumental activities of daily living (OARS-IADL), Reintegration to Normal Living (RNL), and the SF-36 Mental Health component. RESULTS: The total length of stay for the home group was, on average, 10 days, 6 days shorter than that for the usual care group. There were no differences between the 2 groups on the BI or on the TUG at either 1 or 3 months after stroke; however, there was a significantly beneficial impact of the home intervention on IADL and reintegration (RNL). By 3 months after stroke, the home intervention group showed a significantly higher score on the SF-36 Physical Health component than the usual care group. The total number of services received by the home group was actually lower than that received by the usual care group. CONCLUSIONS: Prompt discharge combined with home rehabilitation appeared to translate motor and functional gains that occur through natural recovery and rehabilitation into a greater degree of higher-level function and satisfaction with community reintegration, and these in turn were translated into a better physical health.

Disablement following stroke.

PURPOSE: Stroke is the most disabling chronic condition, newly affecting 35000 persons in Canada each year. Because of declining fatality, a growing number of persons will have to cope with stroke-related disability. The purpose of this paper is to describe the disabilities experienced by persons with stroke during the first year and explore the evolution of impairment, disability, handicap and health-related quality of life. SUBJECTS: The data for this paper come from a series of longitudinal and cross-sectional studies, collectively known as the McGill Stroke Rehabilitation Research Program. RESULTS: Within the first week post-stroke, getting out of bed and walking over a short distance, even with assistance, was a strong predictor of discharge home. Most of the improvement in measures of impairment and disability occurred during the first month and, by 3 months, there was still considerable room for improvement in all measures: 85% of persons were still impaired on gait speed, 78% had not reached age-specific norms for upper extremity function, 68% still demonstrated slow physical mobility, 37% needed some assistance with basic activities of daily living and 29% were still impaired on balance. By 1 year, 73% of persons scored the maximum for basic activities of daily living but 51 and 67% of persons reported their physical health and mental health to be lower than expected. Among a hardy group of stroke survivors, still living in the community 1 year post-stroke, the most striking area of difficulty was endurance, as measured by the 6 minute walk test. Those subjects well enough to complete this task (50% of sample) were able to walk, on average, only 250 metres, equivalent to 40% of their predicted ability. This series of snapshots taken at different points in time suggests that much of the improvement in impairment and disability occurs during the first month and then reaches a plateau. Handicap and quality of life continue to be issues later. Rehabilitation strategies need to consider the multifaceted nature of disablement, which in itself changes with time post-stroke.

Assessing quality of life in clinical research: from where have we come and where are we going?

The term "quality of life" first surfaced in 1920, but it was not until the 1960s that it came to public notice in North America. This article describes the history of quality of life assessment, discusses its current status, and suggests challenges for the future. The development of generic measures began in the early 1970s and continues today. Disease-specific measures have also proliferated. The 1980s and 1990s saw an increase in methodological rigor, and additional emphasis on analytic approaches, interpretation of scale scores, cultural and language issues, as well as on the development of shorter measures. Future challenges include conceptualization and testing of theoretical models, further refinement of individualized measures for use in routine clinical practice, the use of computer adapted testing in quality of life assessment, and the inclusion of quality of life information in health databases.