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1.  Prescriptions for medical research. I--Management within the Medical Research Council. 
BMJ : British Medical Journal  1993;306(6893):1668-1672.
In their submission to the government in advance of the white paper on science policy in the United Kingdom the Medical Research Council commends the MRC's own approach to managing directly funded research. But a series of semi-structured interviews with the directors of some of the MRC's units suggests a gap between the MRC's model of managed research and the reality. Although such units are theoretically managed from MRC head office (and units are charged an overhead for this), in practice each unit runs its own affairs. Between major reviews average contact time with the head office contact person is seven hours a year. The first paper argues that a purchaser-provider split would recognise the benefits of decentralisation and allow units to bid for research funds from several sources, the successful ones guaranteeing their survival through a rolling series of research programmes. The second paper criticises the MRC's cumbersome peer review system. Reliance on outside experts atrophies the scientific skills of head office staff and builds delays into decision making. A purchaser-provider model would allow the head office scientific staff to act like commercial research and development managers, commissioning research, and using the outcome, rather than peer review, as a criterion for continued funding.
PMCID: PMC1678049  PMID: 8324441
2.  Features of COPD patients by comparing CAT with mMRC: a retrospective, cross-sectional study 
Background:
The group assignment of chronic obstructive pulmonary disease (COPD) may differ depending on whether the COPD assessment test (CAT) or modified Medical Research Council dyspnoea scale (mMRC) is used.
Aims:
This study intended to clarify how different patient characteristics influence the differences, to determine the relationships between CAT and mMRC and to characterise COPD patients by both CAT and mMRC.
Methods:
This was a retrospective, cross-sectional study. The data, collected by Taiwan Obstructive Lung Disease consortium, were managed and analysed.
Results:
Of the 757 participants, COPD group assignment was not identical as well as no substantial agreement presented when categorised based on the cut-point CAT score ⩾10 and each mMRC cut-point. In all, 38.2% of participants had discordant group assignments together with a lower mean CAT score, less severe airway obstruction and less severe airflow limitation compared with those with concordant group assignments. In the discordant group, the CAT⩾10/mMRC 0–1 subgroup had more wheezing than CAT<10/mMRC⩾2 subgroup. Only moderate correlations existed between CAT and mMRC. More-symptom groups and combined high-risk group had better correlations than less-symptom groups and combined low-risk group, respectively. A modest negative correlation existed between forced expiratory volume in 1 s percentage (FEV1%) predicted and CAT score and between FEV1% predicted and mMRC scale in parallel with a significant positive relationship existing between the CAT score and mMRC scale. Notably, a significant proportion of COPD patients with each scale of mMRC had health status impairment.
Conclusions:
The Global initiative for Chronic Obstructive Lung Disease committee should redefine the applications of CAT and mMRC in the management of COPD.
doi:10.1038/npjpcrm.2015.63
PMCID: PMC4633725  PMID: 26538368
3.  Exploring the role and function of trial steering committees: results of an expert panel meeting 
Trials  2015;16:597.
Background
The independent oversight of clinical trials, which is recommended by the Medical Research Council (MRC) Guidelines for Good Clinical Practice, is typically provided by an independent advisory Data Monitoring Committee (DMC) and an independent executive committee, to whom the DMC makes recommendations. The detailed roles and function of this executive committee, known as the Trial Steering Committee (TSC), have not previously been studied or reviewed since those originally proposed by the MRC in 1998.
Methods
An expert panel (n = 7) was convened comprising statisticians, clinicians and trial methodologists with prior TSC experience. Twelve questions about the role and responsibilities of the TSC were discussed by the panel at two full-day meetings. Each meeting was transcribed in full and the discussions were summarised.
Results
The expert panel reached agreement on the role of the TSC, to which it was accountable, the membership, the definition of independence, and the experience and training needed. The management of ethical issues, difficult/complex situations and issues the TSC should not ask the DMC to make recommendations on were more difficult to discuss without specific examples, but support existed for further work to help share issues and to provide appropriate training for TSC members. Additional topics discussed, which had not been identified by previous work relating to the DMCs but were pertinent to the role of the TSC, included the following: review of data sharing requests, indemnity, lifespan of the TSC, general TSC administration, and the roles of both the Funder and the Sponsor.
Conclusions
This paper presents recommendations that will contribute to the revision and update of the MRC TSC terms of reference. Uncertainty remains in some areas due to the absence of real-life examples; future guidance on these issues would benefit from a repository of case studies. Notably, the role of a patient and public involvement (PPI) contributor was not discussed, and further work is warranted to explore the role of a PPI contributor in independent trial oversight.
Electronic supplementary material
The online version of this article (doi:10.1186/s13063-015-1125-z) contains supplementary material, which is available to authorized users.
doi:10.1186/s13063-015-1125-z
PMCID: PMC4696246  PMID: 26715378
Trials; oversight committee; trial steering committee; executive committee; clinical trial; data monitoring committee; terms of reference; randomised controlled trial
4.  KEEPING THE CULTURE ALIVE 
This paper reports results from a detailed study of the careers of laboratory technicians in British medical research. Technicians and their contributions are very frequently missing from accounts of modern medicine, and this project is an attempt to correct that absence. The present paper focuses almost entirely on the Medical Research Council’s National Institute for Medical Research in North London, from the first proposal of such a body in 1913 until the mid 1960s. The principal sources of information have been technical staff themselves, largely as recorded in an extensive series of oral history interviews. These have covered a wide range of issues and provide valuable perspectives about technicians’ backgrounds and working lives.
PMCID: PMC2628576  PMID: 18548906
medical laboratory technicians; medical laboratories; medical history
5.  How should individual participant data (IPD) from publicly funded clinical trials be shared? 
BMC Medicine  2015;13:298.
Background
Individual participant data (IPD) from completed clinical trials should be responsibly shared to support efficient clinical research, generate new knowledge and bring benefit to patients. The Medical Research Council (MRC) Hubs for Trials Methodology Research (HTMR) has developed guidance to facilitate the sharing of IPD from publicly funded clinical trials.
Methods
Development of the guidance was completed over four phases which included a focussed review of policy documents, a web-based survey of the UK Clinical Research Collaboration (CRC) Registered Clinical Trials Units (CTU) Network, participation of an expert committee and an open consultation with the UKCRC Registered CTU Network. The project was funded by the MRC HTMR (MR/L004933/1-R39).
Results
Good practice principles include: (i) the use of a controlled access approach, using a transparent and robust system to review requests and provide secure data access; (ii) seeking consent for sharing IPD from trial participants in all future clinical trials with adequate assurance that patient privacy and confidentiality can be maintained; and (iii) establishing an approach to resource the sharing of IPD which would include support from trial funders, sponsor organisations and users of IPD. The guidance has been endorsed by Cancer Research UK, MRC Methodology Research Programme Advisory Group, Wellcome Trust and the Executive Group of the UKCRC Registered CTU Network. The National Institute for Health Research (NIHR) has confirmed it is supportive of the application of this guidance.
Conclusions
Implementation of these principles will improve transparency, increase the coherent sharing of IPD from publicly funded trials, and help publicly funded trials to adhere to trial funder and journal requirements for data sharing.
Electronic supplementary material
The online version of this article (doi:10.1186/s12916-015-0532-z) contains supplementary material, which is available to authorized users.
doi:10.1186/s12916-015-0532-z
PMCID: PMC4682216  PMID: 26675031
Data sharing; Individual participant data; IPD; Clinical trial; Publicly funded; CTU; Good practice
6.  Modified Medical Research Council scale vs Baseline Dyspnea Index to evaluate dyspnea in chronic obstructive pulmonary disease 
Background
Assessment of dyspnea in COPD patients relies in clinical practice on the modified Medical Research Council (mMRC) scale, whereas the Baseline Dyspnea Index (BDI) is mainly used in clinical trials. Little is known on the correspondence between the two methods.
Methods
Cross-sectional analysis was carried out on data from the French COPD cohort Initiatives BPCO. Dyspnea was assessed by the mMRC scale and the BDI. Spirometry, plethysmography, Hospital Anxiety-Depression Scale, St George’s Respiratory Questionnaire, exacerbation rates, and physician-diagnosed comorbidities were obtained. Correlations between mMRC and BDI scores were assessed using Spearman’s correlation coefficient. An ordinal response model was used to examine the contribution of clinical data and lung function parameters to mMRC and BDI scores.
Results
Data are given as median (interquartile ranges, [IQR]). Two-hundred thirty-nine COPD subjects were analyzed (men 78%, age 65.0 years [57.0; 73.0], forced expiratory volume in 1 second [FEV1] 48% predicted [34; 67]). The mMRC grade and BDI score were, respectively, 1 [1–3] and 6 [4–8]. Both BDI and mMRC scores were significantly correlated at the group level (rho =−0.67; P<0.0001), but analysis of individual data revealed a large scatter of BDI scores for any given mMRC grade. In multivariate analysis, both mMRC grade and BDI score were independently associated with lower FEV1% pred, higher exacerbation rate, obesity, depression, heart failure, and hyperinflation, as assessed by the inspiratory capacity/total lung capacity ratio. The mMRC dyspnea grade was also associated with the thromboembolic history and low body mass index.
Conclusion
Dyspnea is a complex symptom with multiple determinants in COPD patients. Although related to similar factors (including hyperinflation, depression, and heart failure), BDI and mMRC scores likely explore differently the dyspnea intensity in COPD patients and are clearly not interchangeable.
doi:10.2147/COPD.S82408
PMCID: PMC4547644  PMID: 26316740
dyspnea; COPD; mMRC; BDI; quality of life; hyperinflation; depression; comorbidities
7.  Three Decades of Research on Computer Applications in Health Care 
The Agency for Healthcare Research and Quality and its predecessor organizations—collectively referred to here as AHRQ—have a productive history of funding research and development in the field of medical informatics, with grant investments since 1968 totaling $107 million. Many computerized interventions that are commonplace today, such as drug interaction alerts, had their genesis in early AHRQ initiatives.
This review provides a historical perspective on AHRQ investment in medical informatics research. It shows that grants provided by AHRQ resulted in achievements that include advancing automation in the clinical laboratory and radiology, assisting in technology development (computer languages, software, and hardware), evaluating the effectiveness of computer-based medical information systems, facilitating the evolution of computer-aided decision making, promoting computer-initiated quality assurance programs, backing the formation and application of comprehensive data banks, enhancing the management of specific conditions such as HIV infection, and supporting health data coding and standards initiatives.
Other federal agencies and private organizations have also supported research in medical informatics, some earlier and to a greater degree than AHRQ. The results and relative roles of these related efforts are beyond the scope of this review.
doi:10.1197/jamia.M0867
PMCID: PMC344572  PMID: 11861630
8.  Experiences of Accreditation of Medical Education in Taiwan 
This review aims to introduce the Taiwanese Medical Accreditation System: its history, role and future goals. In 1999, the Ministry of Education, Taiwanese Government commissioned the non-profit National Health Research Institutes (NHRI) to develop a new medical accreditation system. According to that policy, the Taiwan Medical Accreditation Council (TMAC) was established in the same year. The council serves a similar function to that of the Liaison Committee on Medical Education (LCME) of the United States and the Australian Medical Council (AMC). The accreditation process consists of a self-assessment plus a four-day site visit by a team of eight medical educators that are headed by one of the council members of the TMAC. The first cycle of initial visits was completed from 2001 to 2004. Subsequent follow-up visits were arranged according to the results of the survey with smaller-sized teams and shorter periods. There is evidence to suggest that the majority (seven of eleven) of the medical schools in Taiwan have made good progress. TMAC's next step will be to monitor the progress and raise the standard of medical education in individual schools with a homogenous, superior standard of medical education.
doi:10.3352/jeehp.2009.6.2
PMCID: PMC2796724  PMID: 20046455
Accreditation; Medical Education; Taiwan
9.  The Prevalence of Quadriceps Weakness in COPD and the Relationship with Disease Severity 
Rationale and objectives
Quadriceps strength relates to exercise capacity and prognosis in chronic obstructive pulmonary disease (COPD). We wished to quantify the prevalence of quadriceps weakness in COPD, and hypothesised that it would not be restricted to patients with severe airflow obstruction or dyspnoea.
Methods
Predicted quadriceps strength was calculated using a regression equation (incorporating age, gender, height and fat-free mass), based on measurements from 212 healthy subjects. The prevalence of weakness (defined as observed values 1.645 standardised residuals below predicted) was related to GOLD stage and Medical Research Council (MRC) dyspnoea score in two cohorts of stable COPD outpatients recruited from the United Kingdom (n=240) and the Netherlands (n=351).
Main results
32% and 33% of UK and Dutch COPD patients had quadriceps weakness. A significant proportion of patients in GOLD stages 1 and 2, or with an MRC dyspnoea score of 1 or 2, had quadriceps weakness (28% and 26% respectively). These values rose to 38% in GOLD stage 4, and 43% in patients with an MRC Score of 4 or 5.
Conclusion
Quadriceps weakness was demonstrable in one-third of COPD patients attending hospital respiratory outpatient services. Quadriceps weakness exists in the absence of severe airflow obstruction or breathlessness.
doi:10.1183/09031936.00104909
PMCID: PMC3039205  PMID: 19897554
10.  Keeping the culture alive: the laboratory technician in mid-twentieth-century British medical research 
This paper reports results from a detailed study of the careers of laboratory technicians in British medical research. Technicians and their contributions are very frequently missing from accounts of modern medicine, and this project is an attempt to correct that absence. The present paper focuses almost entirely on the Medical Research Council's National Institute for Medical Research in North London, from the first proposal of such a body in 1913 until the mid 1960s. The principal sources of information have been technical staff themselves, largely as recorded in an extensive series of oral history interviews. These have covered a wide range of issues and provide valuable perspectives about technicians' backgrounds and working lives.
doi:10.1098/rsnr.2007.0035
PMCID: PMC2628576  PMID: 18548906
medical laboratory technicians; medical laboratories; medical history
11.  Models and impact of patient and public involvement in studies carried out by the Medical Research Council Clinical Trials Unit at University College London: findings from ten case studies 
Trials  2016;17:376.
Background
Patient and public involvement (PPI) in studies carried out by the UK Medical Research Council Clinical Trials Unit (MRC CTU) at University College London varies by research type and setting. We developed a series of case studies of PPI to document and share good practice.
Methods
We used purposive sampling to identify studies representing the scope of research at the MRC CTU and different approaches to PPI. We carried out semi-structured interviews with staff and patient representatives. Interview notes were analysed descriptively to categorise the main aims and motivations for involvement; activities undertaken; their impact on the studies and lessons learned.
Results
We conducted 19 interviews about ten case studies, comprising one systematic review, one observational study and 8 randomised controlled trials in HIV and cancer. Studies were either open or completed, with start dates between 2003 and 2011. Interviews took place between March and November 2014 and were updated in summer 2015 where there had been significant developments in the study (i.e. if the study had presented results subsequent to the interview taking place). A wide range of PPI models, including representation on trial committees or management groups, community engagement, one-off task-focused activities, patient research partners and participant involvement had been used. Overall, interviewees felt that PPI had a positive impact, leading to improvements, for example in the research question; study design; communication with potential participants; study recruitment; confidence to carry out or complete a study; interpretation and communication of results; and influence on future research.
Conclusions
A range of models of PPI can benefit clinical studies. Researchers should consider different approaches to PPI, based on the desired impact and the people they want to involve. Use of multiple models may increase the potential impacts of PPI in clinical research.
Electronic supplementary material
The online version of this article (doi:10.1186/s13063-016-1488-9) contains supplementary material, which is available to authorized users.
doi:10.1186/s13063-016-1488-9
PMCID: PMC4966697  PMID: 27473060
Patient and public involvement; Consumer involvement; Clinical trials; Systematic reviews; RCTs
12.  Systematic techniques for assisting recruitment to trials (START): study protocol for embedded, randomized controlled trials 
Trials  2014;15:407.
Background
Randomized controlled trials play a central role in evidence-based practice, but recruitment of participants, and retention of them once in the trial, is challenging. Moreover, there is a dearth of evidence that research teams can use to inform the development of their recruitment and retention strategies. As with other healthcare initiatives, the fairest test of the effectiveness of a recruitment strategy is a trial comparing alternatives, which for recruitment would mean embedding a recruitment trial within an ongoing host trial. Systematic reviews indicate that such studies are rare. Embedded trials are largely delivered in an ad hoc way, with interventions almost always developed in isolation and tested in the context of a single host trial, limiting their ability to contribute to a body of evidence with regard to a single recruitment intervention and to researchers working in different contexts.
Methods/Design
The Systematic Techniques for Assisting Recruitment to Trials (START) program is funded by the United Kingdom Medical Research Council (MRC) Methodology Research Programme to support the routine adoption of embedded trials to test standardized recruitment interventions across ongoing host trials. To achieve this aim, the program involves three interrelated work packages: (1) methodology - to develop guidelines for the design, analysis and reporting of embedded recruitment studies; (2) interventions - to develop effective and useful recruitment interventions; and (3) implementation - to recruit host trials and test interventions through embedded studies.
Discussion
Successful completion of the START program will provide a model for a platform for the wider trials community to use to evaluate recruitment interventions or, potentially, other types of intervention linked to trial conduct. It will also increase the evidence base for two types of recruitment intervention.
Trial registration
The START protocol covers the methodology for embedded trials. Each embedded trial is registered separately or as a substudy of the host trial.
doi:10.1186/1745-6215-15-407
PMCID: PMC4230578  PMID: 25344684
Randomized controlled trial; Recruitment; Primary care; Community; Trial participation; Intervention; Multimedia; Decision support systems; Protocols; Participant information
13.  Implementing a training intervention to support caregivers after stroke: a process evaluation examining the initiation and embedding of programme change 
Background
Medical Research Council (MRC) guidance identifies implementation as a key element of the development and evaluation process for complex healthcare interventions. Implementation is itself a complex process involving the mobilization of human, material, and organizational resources to change practice within settings that have pre-existing structures, historical patterns of relationships, and routinized ways of working. Process evaluations enable researchers and clinicians to understand how implementation proceeds and what factors impact on intended program change. A qualitative process evaluation of the pragmatic cluster randomized controlled trial; Training Caregivers after Stroke was conducted to examine how professionals were engaged in the work of delivering training; how they reached and involved caregivers for whom the intervention was most appropriate; how did those on whom training was targeted experience and respond to it. Normalization Process Theory, which focuses attention on implementing and embedding program change, was used as a sensitizing framework to examine selected findings.
Results
Contextual factors including organizational history and team relationships, external policy, and service development initiatives, impinged on implementation of the caregiver training program in unintended ways that could not have been predicted through focus on mechanisms of individual and collective action at unit level. Factors that facilitated or impeded the effectiveness of the cascade training model used, whether and how stroke unit teams made sense of and engaged individually and collectively with a complex caregiver training intervention, and what impact these factors had on embedding the intervention in routine stroke unit practice were identified.
Conclusions
Where implementation of complex interventions depends on multiple providers, time needs to be invested in reaching agreement on who will take responsibility for delivery of specific components and in determining how implementation and its effectiveness will be monitored. This goes beyond concern with intervention fidelity; explicit consideration also needs to be given to the implementation process in terms of how program change can be effected at organizational, practice, and service delivery levels. Normalization Process Theory’s constructs help identify vulnerable features of implementation processes in respect of the work involved in embedding complex interventions.
doi:10.1186/1748-5908-8-96
PMCID: PMC3765868  PMID: 23972027
Process evaluation; Implementation theory; Stroke; Caregiver training; Normalization process theory
14.  Implementing the 2009 Institute of Medicine recommendations on resident physician work hours, supervision, and safety 
Long working hours and sleep deprivation have been a facet of physician training in the US since the advent of the modern residency system. However, the scientific evidence linking fatigue with deficits in human performance, accidents and errors in industries from aeronautics to medicine, nuclear power, and transportation has mounted over the last 40 years. This evidence has also spawned regulations to help ensure public safety across safety-sensitive industries, with the notable exception of medicine.
In late 2007, at the behest of the US Congress, the Institute of Medicine embarked on a year-long examination of the scientific evidence linking resident physician sleep deprivation with clinical performance deficits and medical errors. The Institute of Medicine’s report, entitled “Resident duty hours: Enhancing sleep, supervision and safety”, published in January 2009, recommended new limits on resident physician work hours and workload, increased supervision, a heightened focus on resident physician safety, training in structured handovers and quality improvement, more rigorous external oversight of work hours and other aspects of residency training, and the identification of expanded funding sources necessary to implement the recommended reforms successfully and protect the public and resident physicians themselves from preventable harm.
Given that resident physicians comprise almost a quarter of all physicians who work in hospitals, and that taxpayers, through Medicare and Medicaid, fund graduate medical education, the public has a deep investment in physician training. Patients expect to receive safe, high-quality care in the nation’s teaching hospitals. Because it is their safety that is at issue, their voices should be central in policy decisions affecting patient safety. It is likewise important to integrate the perspectives of resident physicians, policy makers, and other constituencies in designing new policies. However, since its release, discussion of the Institute of Medicine report has been largely confined to the medical education community, led by the Accreditation Council for Graduate Medical Education (ACGME).
To begin gathering these perspectives and developing a plan to implement safer work hours for resident physicians, a conference entitled “Enhancing sleep, supervision and safety: What will it take to implement the Institute of Medicine recommendations?” was held at Harvard Medical School on June 17–18, 2010. This White Paper is a product of a diverse group of 26 representative stakeholders bringing relevant new information and innovative practices to bear on a critical patient safety problem. Given that our conference included experts from across disciplines with diverse perspectives and interests, not every recommendation was endorsed by each invited conference participant. However, every recommendation made here was endorsed by the majority of the group, and many were endorsed unanimously. Conference members participated in the process, reviewed the final product, and provided input before publication. Participants provided their individual perspectives, which do not necessarily represent the formal views of any organization.
In September 2010 the ACGME issued new rules to go into effect on July 1, 2011. Unfortunately, they stop considerably short of the Institute of Medicine’s recommendations and those endorsed by this conference. In particular, the ACGME only applied the limitation of 16 hours to first-year resident physicans. Thus, it is clear that policymakers, hospital administrators, and residency program directors who wish to implement safer health care systems must go far beyond what the ACGME will require. We hope this White Paper will serve as a guide and provide encouragement for that effort.
Resident physician workload and supervision
By the end of training, a resident physician should be able to practice independently. Yet much of resident physicians’ time is dominated by tasks with little educational value. The caseload can be so great that inadequate reflective time is left for learning based on clinical experiences. In addition, supervision is often vaguely defined and discontinuous. Medical malpractice data indicate that resident physicians are frequently named in lawsuits, most often for lack of supervision. The recommendations are: The ACGME should adjust resident physicians workload requirements to optimize educational value. Resident physicians as well as faculty should be involved in work redesign that eliminates nonessential and noneducational activity from resident physician dutiesMechanisms should be developed for identifying in real time when a resident physician’s workload is excessive, and processes developed to activate additional providersTeamwork should be actively encouraged in delivery of patient care. Historically, much of medical training has focused on individual knowledge, skills, and responsibility. As health care delivery has become more complex, it will be essential to train resident and attending physicians in effective teamwork that emphasizes collective responsibility for patient care and recognizes the signs, both individual and systemic, of a schedule and working conditions that are too demanding to be safeHospitals should embrace the opportunities that resident physician training redesign offers. Hospitals should recognize and act on the potential benefits of work redesign, eg, increased efficiency, reduced costs, improved quality of care, and resident physician and attending job satisfactionAttending physicians should supervise all hospital admissions. Resident physicians should directly discuss all admissions with attending physicians. Attending physicians should be both cognizant of and have input into the care patients are to receive upon admission to the hospitalInhouse supervision should be required for all critical care services, including emergency rooms, intensive care units, and trauma services. Resident physicians should not be left unsupervised to care for critically ill patients. In settings in which the acuity is high, physicians who have completed residency should provide direct supervision for resident physicians. Supervising physicians should always be physically in the hospital for supervision of resident physicians who care for critically ill patientsThe ACGME should explicitly define “good” supervision by specialty and by year of training. Explicit requirements for intensity and level of training for supervision of specific clinical scenarios should be providedCenters for Medicare and Medicaid Services (CMS) should use graduate medical education funding to provide incentives to programs with proven, effective levels of supervision. Although this action would require federal legislation, reimbursement rules would help to ensure that hospitals pay attention to the importance of good supervision and require it from their training programs
Resident physician work hours
Although the IOM “Sleep, supervision and safety” report provides a comprehensive review and discussion of all aspects of graduate medical education training, the report’s focal point is its recommendations regarding the hours that resident physicians are currently required to work. A considerable body of scientific evidence, much of it cited by the Institute of Medicine report, describes deteriorating performance in fatigued humans, as well as specific studies on resident physician fatigue and preventable medical errors.
The question before this conference was what work redesign and cultural changes are needed to reform work hours as recommended by the Institute of Medicine’s evidence-based report? Extensive scientific data demonstrate that shifts exceeding 12–16 hours without sleep are unsafe. Several principles should be followed in efforts to reduce consecutive hours below this level and achieve safer work schedules. The recommendations are: Limit resident physician work hours to 12–16 hour maximum shiftsA minimum of 10 hours off duty should be scheduled between shiftsResident physician input into work redesign should be actively solicitedSchedules should be designed that adhere to principles of sleep and circadian science; this includes careful consideration of the effects of multiple consecutive night shifts, and provision of adequate time off after night work, as specified in the IOM reportResident physicians should not be scheduled up to the maximum permissible limits; emergencies frequently occur that require resident physicians to stay longer than their scheduled shifts, and this should be anticipated in scheduling resident physicians’ work shiftsHospitals should anticipate the need for iterative improvement as new schedules are initiated; be prepared to learn from the initial phase-in, and change the plan as neededAs resident physician work hours are redesigned, attending physicians should also be considered; a potential consequence of resident physician work hour reduction and increased supervisory requirements may be an increase in work for attending physicians; this should be carefully monitored, and adjustments to attending physician work schedules made as needed to prevent unsafe work hours or working conditions for this group“Home call” should be brought under the overall limits of working hours; work load and hours should be monitored in each residency program to ensure that resident physicians and fellows on home call are getting sufficient sleepMedicare funding for graduate medical education in each hospital should be linked with adherence to the Institute of Medicine limits on resident physician work hours
Moonlighting by resident physicians
The Institute of Medicine report recommended including external as well as internal moonlighting in working hour limits. The recommendation is: All moonlighting work hours should be included in the ACGME working hour limits and actively monitored. Hospitals should formalize a moonlighting policy and establish systems for actively monitoring resident physician moonlighting
Safety of resident physicians
The “Sleep, supervision and safety” report also addresses fatigue-related harm done to resident physicians themselves. The report focuses on two main sources of physical injury to resident physicians impaired by fatigue, ie, needle-stick exposure to blood-borne pathogens and motor vehicle crashes. Providing safe transportation home for resident physicians is a logistical and financial challenge for hospitals. Educating physicians at all levels on the dangers of fatigue is clearly required to change driving behavior so that safe hospital-funded transport home is used effectively. Fatigue-related injury prevention (including not driving while drowsy) should be taught in medical school and during residency, and reinforced with attending physicians; hospitals and residency programs must be informed that resident physicians’ ability to judge their own level of impairment is impaired when they are sleep deprived; hence, leaving decisions about the capacity to drive to impaired resident physicians is not recommendedHospitals should provide transportation to all resident physicians who report feeling too tired to drive safely; in addition, although consecutive work should not exceed 16 hours, hospitals should provide transportation for all resident physicians who, because of unforeseen reasons or emergencies, work for longer than consecutive 24 hours; transportation under these circumstances should be automatically provided to house staff, and should not rely on self-identification or request
Training in effective handovers and quality improvement
Handover practice for resident physicians, attendings, and other health care providers has long been identified as a weak link in patient safety throughout health care settings. Policies to improve handovers of care must be tailored to fit the appropriate clinical scenario, recognizing that information overload can also be a problem. At the heart of improving handovers is the organizational effort to improve quality, an effort in which resident physicians have typically been insufficiently engaged. The recommendations are: Hospitals should train attending and resident physicians in effective handovers of careHospitals should create uniform processes for handovers that are tailored to meet each clinical setting; all handovers should be done verbally and face-to-face, but should also utilize written toolsWhen possible, hospitals should integrate hand-over tools into their electronic medical records (EMR) systems; these systems should be standardized to the extent possible across residency programs in a hospital, but may be tailored to the needs of specific programs and services; federal government should help subsidize adoption of electronic medical records by hospitals to improve signoutWhen feasible, handovers should be a team effort including nurses, patients, and familiesHospitals should include residents in their quality improvement and patient safety efforts; the ACGME should specify in their core competency requirements that resident physicians work on quality improvement projects; likewise, the Joint Commission should require that resident physicians be included in quality improvement and patient safety programs at teaching hospitals; hospital administrators and residency program directors should create opportunities for resident physicians to become involved in ongoing quality improvement projects and root cause analysis teams; feedback on successful quality improvement interventions should be shared with resident physicians and broadly disseminatedQuality improvement/patient safety concepts should be integral to the medical school curriculum; medical school deans should elevate the topics of patient safety, quality improvement, and teamwork; these concepts should be integrated throughout the medical school curriculum and reinforced throughout residency; mastery of these concepts by medical students should be tested on the United States Medical Licensing Examination (USMLE) stepsFederal government should support involvement of resident physicians in quality improvement efforts; initiatives to improve quality by including resident physicians in quality improvement projects should be financially supported by the Department of Health and Human Services
Monitoring and oversight of the ACGME
While the ACGME is a key stakeholder in residency training, external voices are essential to ensure that public interests are heard in the development and monitoring of standards. Consequently, the Institute of Medicine report recommended external oversight and monitoring through the Joint Commission and Centers for Medicare and Medicaid Services (CMS). The recommendations are: Make comprehensive fatigue management a Joint Commission National Patient Safety Goal; fatigue is a safety concern not only for resident physicians, but also for nurses, attending physicians, and other health care workers; the Joint Commission should seek to ensure that all health care workers, not just resident physicians, are working as safely as possibleFederal government, including the Centers for Medicare and Medicaid Services and the Agency for Healthcare Research and Quality, should encourage development of comprehensive fatigue management programs which all health systems would eventually be required to implementMake ACGME compliance with working hours a “ condition of participation” for reimbursement of direct and indirect graduate medical education costs; financial incentives will greatly increase the adoption of and compliance with ACGME standards
Future financial support for implementation
The Institute of Medicine’s report estimates that $1.7 billion (in 2008 dollars) would be needed to implement its recommendations. Twenty-five percent of that amount ($376 million) will be required just to bring hospitals into compliance with the existing 2003 ACGME rules. Downstream savings to the health care system could potentially result from safer care, but these benefits typically do not accrue to hospitals and residency programs, who have been asked historically to bear the burden of residency reform costs. The recommendations are: The Institute of Medicine should convene a panel of stakeholders, including private and public funders of health care and graduate medical education, to lay down the concrete steps necessary to identify and allocate the resources needed to implement the recommendations contained in the IOM “Resident duty hours: Enhancing sleep, supervision and safety” report. Conference participants suggested several approaches to engage public and private support for this initiativeEfforts to find additional funding to implement the Institute of Medicine recommendations should focus more broadly on patient safety and health care delivery reform; policy efforts focused narrowly upon resident physician work hours are less likely to succeed than broad patient safety initiatives that include residency redesign as a key componentHospitals should view the Institute of Medicine recommendations as an opportunity to begin resident physician work redesign projects as the core of a business model that embraces safety and ultimately saves resourcesBoth the Secretary of Health and Human Services and the Director of the Centers for Medicare and Medicaid Services should take the Institute of Medicine recommendations into consideration when promulgating rules for innovation grantsThe National Health Care Workforce Commission should consider the Institute of Medicine recommendations when analyzing the nation’s physician workforce needs
Recommendations for future research
Conference participants concurred that convening the stakeholders and agreeing on a research agenda was key. Some observed that some sectors within the medical education community have been reluctant to act on the data. Several logical funders for future research were identified. But above all agencies, Centers for Medicare and Medicaid Services is the only stakeholder that funds graduate medical education upstream and will reap savings downstream if preventable medical errors are reduced as a result of reform of resident physician work hours.
doi:10.2147/NSS.S19649
PMCID: PMC3630963  PMID: 23616719
resident; hospital; working hours; safety
15.  A Guide for Health Professionals Working with Aboriginal Peoples: Executive Summary 
Objective
to provide Canadian health professionals with a network of information and recommendations regarding Aboriginal health.
Options
health professionals working with Aboriginal individuals and communities in the area of women’s health care.
Outcomes
improved health status of Aboriginal peoples in Canada.
Appropriateness and accessibility of women’s health services for Aboriginal peoples.
Improved communication and clinical skills of health professionals in the area of Aboriginal health.
Improved quality of relationship between health professionals and Aboriginal individuals and communities.
Improved quality of relationship between health care professionals and Aboriginal individuals and communities.
Evidence
recommendations are based on expert opinion and a review of the literature. Published references were identified by a Medline search of all review articles, randomized clinical control trials, meta-analyses, and practice guidelines from 1966 to February 1999, using the MeSH headings “Indians, North American or Eskimos” and “Health.”* Subsequently published articles were brought to the attention of the authors in the process of writing and reviewing the document. Ancillary and unpublished references were recommended by members of the SOGC Aboriginal Health Issues Committee and the panel of expert reviewers.
Values
information collected was reviewed by the principal author. The social, cultural, political, and historic context of Aboriginal peoples in Canada, systemic barriers regarding the publication of information by Aboriginal authors, the diversity of Aboriginal peoples in Canada, and the need for a culturally appropriate and balanced presentation were carefully considered in addition to more traditional scientific evaluation. The majority of information collected consisted of descriptive health and social information and such evaluation tools as the evidence guidelines of the Canadian Task Force on the Periodic Health exam were not appropriate.
Benefits, costs, and harms
utilization of the information and recommendations by Canadian health professionals will enhance understanding, communication, and clinical skills in the area of Aboriginal health. The resulting enhancement of collaborative relationships between Aboriginal peoples and their women’s health providers may contribute to health services that are more appropriate, effective, efficient, and accessible for Aboriginal peoples in Canada. The educational process may require an initial investment of time from the health professional.
Recommendations
Recommendations were grouped according to four themes: sociocultural context, health concerns, cross-cultural understanding, and Aboriginal health resources. Health professionals are encouraged to learn the appropriate names, demographics, and traditional geographic territories and language groups of the various Aboriginal groups in Canada. In addition, sensitivity to the impact of colonization and current socioeconomic challenges to the health status of Aboriginal peoples is warranted. Health services for Aboriginal peoples should take place as close to home as possible. Governmental obligations and policies regarding determination are recognized. With respect to health concerns, holistic definitions of health, based on Aboriginal perspectives, are put forward. Aboriginal peoples continue to experience a disproportionate burden of health problems. Health professionals are encouraged to become familiar with several key areas of morbidity and mortality. Relationships between Aboriginal peoples and their care providers need to be based on a foundation of mutual respect. Gaps and barriers in the current health care system for Aboriginal peoples are identified. Health professionals are encouraged to work with Aboriginal individuals and communities to address these gaps and barriers. Aboriginal peoples require culturally appropriate health care, including treatment in their own languages when possible. This may require interpreters or Aboriginal health advocates. Health professionals are encouraged to recognize the importance of family and community roles, and to respect traditional medicines and healers. Health professionals can develop their sensitivities towards Aboriginal peoples by participating in workshops, making use of educational resources, and by spending time with Aboriginal peoples in their communities. Aboriginal communities and health professionals are encouraged to support community-based, community-directed health services and health research for Aboriginal peoples. In addition, the education of more Aboriginal health professionals is essential. The need for a preventative approach to health programming in Aboriginal communities is stressed.
Validation
recommendations were reviewed and revised by the SOGC Aboriginal Health Issues Committee, a panel of expert reviewers, and the SOGC Council. In addition, this document was also reviewed and supported by the Assembly of First Nations, Canadian Institute of Child Health, Canadian Paediatric Society, College of Family Physicians of Canada, Congress of Aboriginal Peoples, Federation of Medical Women of Canada, Inuit Tapirisat of Canada, Metis National Council, National Indian and Inuit Community Health Representatives Organization, and Pauktuutit Inuit Women’s Association.
Sponsor
Society of Obstetricians and Gynaecologists of Canada.
PMCID: PMC3653835  PMID: 23682204 CAMSID: cams2752
16.  Predicting Outcome after Traumatic Brain Injury: Development and International Validation of Prognostic Scores Based on Admission Characteristics 
PLoS Medicine  2008;5(8):e165.
Background
Traumatic brain injury (TBI) is a leading cause of death and disability. A reliable prediction of outcome on admission is of great clinical relevance. We aimed to develop prognostic models with readily available traditional and novel predictors.
Methods and Findings
Prospectively collected individual patient data were analyzed from 11 studies. We considered predictors available at admission in logistic regression models to predict mortality and unfavorable outcome according to the Glasgow Outcome Scale at 6 mo after injury. Prognostic models were developed in 8,509 patients with severe or moderate TBI, with cross-validation by omission of each of the 11 studies in turn. External validation was on 6,681 patients from the recent Medical Research Council Corticosteroid Randomisation after Significant Head Injury (MRC CRASH) trial. We found that the strongest predictors of outcome were age, motor score, pupillary reactivity, and CT characteristics, including the presence of traumatic subarachnoid hemorrhage. A prognostic model that combined age, motor score, and pupillary reactivity had an area under the receiver operating characteristic curve (AUC) between 0.66 and 0.84 at cross-validation. This performance could be improved (AUC increased by approximately 0.05) by considering CT characteristics, secondary insults (hypotension and hypoxia), and laboratory parameters (glucose and hemoglobin). External validation confirmed that the discriminative ability of the model was adequate (AUC 0.80). Outcomes were systematically worse than predicted, but less so in 1,588 patients who were from high-income countries in the CRASH trial.
Conclusions
Prognostic models using baseline characteristics provide adequate discrimination between patients with good and poor 6 mo outcomes after TBI, especially if CT and laboratory findings are considered in addition to traditional predictors. The model predictions may support clinical practice and research, including the design and analysis of randomized controlled trials.
Ewout Steyerberg and colleagues describe a prognostic model for the prediction of outcome of traumatic brain injury using data available on admission.
Editors' Summary
Background.
Traumatic brain injury (TBI) causes a large amount of morbidity and mortality worldwide. According to the Centers for Disease Control, for example, about 1.4 million Americans will sustain a TBI—a head injury—each year. Of these, 1.1 million will be treated and released from an emergency department, 235,000 will be hospitalized, and 50,000 will die. The burden of disease is much higher in the developing world, where the causes of TBI such as traffic accidents occur at higher rates and treatment may be less available.
Why Was This Study Done?
Given the resources required to treat TBI, a very useful research tool would be the ability to accurately predict on admission to hospital what the outcome of a given injury might be. Currently, scores such as the Glasgow Coma Scale are useful to predict outcome 24 h after the injury but not before.
Prognostic models are useful for several reasons. Clinically, they help doctors and patients make decisions about treatment. They are also useful in research studies that compare outcomes in different groups of patients and when planning randomized controlled trials. The study presented here is one of a number of analyses done by the IMPACT research group over the past several years using a large database that includes data from eight randomized controlled trials and three observational studies conducted between 1984 and 1997. There are other ongoing studies that also seek to develop new prognostic models; one such recent study was published in BMJ by a group involving the lead author of the PLoS Medicine paper described here.
What Did the Researchers Do and Find?
The authors analyzed data that had been collected prospectively on individual patients from the 11 studies included in the database and derived models to predict mortality and unfavorable outcome at 6 mo after injury for the 8,509 patients with severe or moderate TBI. They found that the strongest predictors of outcome were age, motor score, pupillary reactivity, and characteristics on the CT scan, including the presence of traumatic subarachnoid hemorrhage. A core prognostic model could be derived from the combination of age, motor score, and pupillary reactivity. A better score could be obtained by adding CT characteristics, secondary problems (hypotension and hypoxia), and laboratory measurements of glucose and hemoglobin. The scores were then tested to see how well they predicted outcome in a different group of patients—6,681 patients from the recent Medical Research Council Corticosteroid Randomisation after Significant Head Injury (MRC CRASH) trial.
What Do These Findings Mean?
In this paper the authors show that it is possible to produce prognostic models using characteristics collected on admission as part of routine care that can discriminate between patients with good and poor outcomes 6 mo after TBI, especially if the results from CT scans and laboratory findings are added to basic models. This paper has to be considered together with other studies, especially the paper mentioned above, which was recently published in the BMJ (MRC CRASH Trial Collaborators [2008] Predicting outcome after traumatic brain injury: practical prognostic models based on large cohort of international patients. BMJ 336: 425–429.). The BMJ study presented a set of similar, but subtly different models, with specific focus on patients in developing countries; in that case, the patients in the CRASH trial were used to produce the models, and the patients in the IMPACT database were used to verify one variant of the models. Unfortunately this related paper was not disclosed to us during the initial review process; however, during PLoS Medicine's subsequent consideration of this manuscript we learned of it. After discussion with the reviewers, we took the decision that the models described in the PLoS Medicine paper are sufficiently different from those reported in the other paper and as such proceeded with publication of the paper. Ideally, however, these two sets of models would have been reviewed and published side by side, so that readers could easily evaluate the respective merits and value of the two different sets of models in the light of each other. The two sets of models are, however, discussed in a Perspective article also published in PLoS Medicine (see below).
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050165.
This paper and the BMJ paper mentioned above are discussed further in a PLoS Medicine Perspective article by Andrews and Young
The TBI Impact site provides a tool to calculate the scores described in this paper
The CRASH trial, which is used to validate the scores mentioned here, has a Web site explaining the trial and its results
The R software, which was used for the prognostic analyses, is freely available
The MedlinePlus encyclopedia has information on head injury
The WHO site on neurotrauma discusses head injury from a global perspective
The CDC's National Center for Injury Prevention and Control gives statistics on head injury in the US and advice on prevention
doi:10.1371/journal.pmed.0050165
PMCID: PMC2494563  PMID: 18684008
17.  Biomedical research in Quebec: the history of the Fonds de la recherche en santé du Québec. 
The author describes the history of the Fonds de la recherche en santé du Québec, from after World War II to the present day. The Conseil de la recherche médicale du Québec (Quebec Medical Research Council) was created in 1964 to bring Quebec up to speed in biomedical research through programs that complemented those of the Medical Research Council of Canada. The council progressively evolved, becoming the Conseil de la recherche en santé du Québec (Quebec Health Research Council) in 1974 and the Fonds de la recherche en santé du Québec (FRSQ) in 1982. The FRSQ covers all aspects of medical research, in its broadest sense. Quebec's progress in biomedical research has been spectacular and has had direct and considerable influence on the quality of medical education and patient care. From 1982 to 1996, various Quebec governments have devoted more than +500 million to the FRSQ, a testimony to their comprehension of the importance of this area and to their farsightedness. The FRSQ and its predecessor organizations have been a major force in improving and maintaining the quality of medical teaching and care in Quebec during the last three decades.
PMCID: PMC1335216  PMID: 8823209
18.  Identifying adults at risk of COPD who need confirmatory spirometry in primary care 
Canadian Family Physician  2011;57(2):e51-e57.
Abstract
Objective
To examine the usefulness of a symptom-based case-finding questionnaire (CFQ) and the Medical Research Council (MRC) dyspnea scale in identifying which individuals with known risk factors for chronic obstructive pulmonary disease (COPD) require targeted spirometry in primary care.
Design
Cross-sectional study.
Setting
Three community primary care practices in Ontario.
Participants
Men and women 40 years of age and older with a smoking history of 20 pack-years or more.
Main outcome measures
We administered a CFQ for the presence of cough, sputum, wheeze, dyspnea, and recurrent respiratory infections (possible range of scores from 0 to 5) and applied the MRC dyspnea scale to assess the severity of COPD (possible range of scores from 1 to 5). Spirometric measures of forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were collected, with COPD defined as a postbronchodilator FEV1/FVC of less than 0.7 and FEV1 of less than 80% of the predicted value. Using spirometric data to confirm the diagnosis of COPD, likelihood ratios, pretest and posttest probabilities, and area under a receiver operating characteristic curve were calculated for the total CFQ and MRC scores.
Results
Scores for the CFQ and MRC dyspnea scale were available for 996 and 829 participants, respectively. The likelihood ratios for a total CFQ score of 3 or higher and an MRC dyspnea score of 4 or 5 were 1.82 (95% confidence interval [CI] 1.48 to 2.22) and 4.22 (95% CI 2.08 to 8.56), respectively. The likelihood ratios for a total CFQ score of 2 or less and an MRC dyspnea score of 1 were 0.75 (95% CI 0.66 to 0.85) and 0.50 (95% CI 0.39 to 0.65), respectively. Area under the receiver operating characteristic curve was 0.62 (95% CI 0.58 to 0.67; P < .001) for the total CFQ scores and 0.64 (95% CI 0.60 to 068; P < .001) for the MRC dyspnea scores.
Conclusion
In adults with known risk factors, the likelihood of having moderate to severe COPD is increased in those who report 3 or more common respiratory symptoms and marked functional limitation resulting from dyspnea. However, selecting individuals for spirometry based on symptoms alone will identify less than half of those with moderate to severe COPD.
PMCID: PMC3038833  PMID: 21642706
19.  ‘Saving the lives of our dogs’: the development of canine distemper vaccine in interwar Britain 
This paper examines the successful campaign in Britain to develop canine distemper vaccine between 1922 and 1933. The campaign mobilized disparate groups around the common cause of using modern science to save the nation's dogs from a deadly disease. Spearheaded by landed patricians associated with the country journal The Field, and funded by dog owners and associations, it relied on collaborations with veterinary professionals, government scientists, the Medical Research Council (MRC) and the commercial pharmaceutical house the Burroughs Wellcome Company (BWC). The social organization of the campaign reveals a number of important, yet previously unexplored, features of interwar science and medicine in Britain. It depended on a patronage system that drew upon a large base of influential benefactors and public subscriptions. Coordinated by the Field Distemper Fund, this system was characterized by close relationships between landed elites and their social networks with senior science administrators and researchers. Relations between experts and non-experts were crucial, with high levels of public engagement in all aspects of research and vaccine development. At the same time, experimental and commercial research supported under the campaign saw dynamic interactions between animal and human medicine, which shaped the organization of the MRC's research programme and demonstrated the value of close collaboration between veterinary and medical science, with the dog as a shared object and resource. Finally, the campaign made possible the translation of ‘laboratory’ findings into field conditions and commercial products. Rather than a unidirectional process, translation involved negotiations over the very boundaries of the ‘laboratory’ and the ‘field’, and what constituted a viable vaccine. This paper suggests that historians reconsider standard historical accounts of the nature of patronage, the role of animals, and the interests of landed elites in interwar British science and medicine.
doi:10.1017/S0007087413000344
PMCID: PMC4014013  PMID: 24941736
20.  The Research Council System and the Politics of Medical and Agricultural Research for the British Colonial Empire, 1940–52 
Medical History  2013;57(3):338-358.
Historical accounts of colonial science and medicine have failed to engage with the Colonial Office’s shift in focus towards the support of research after 1940. A large new fund was created in 1940 to expand activities in the colonies described as fundamental research. With this new funding came a qualitative shift in the type of personnel and activity sought for colonial development and, as a result, a diverse group of medical and technical officers existed in Britain’s colonies by the 1950s. The fact that such variety existed amongst British officers in terms of their qualifications, institutional locations and also their relationships with colonial and metropolitan governments makes the use of the term ‘expert’ in much existing historical scholarship on scientific and medical aspects of empire problematic. This article will consider how the Colonial Office achieved this expansion of research activities and personnel after 1940. Specifically, it will focus on the reasons officials sought to engage individuals drawn from the British research councils to administer this work and the consequences of their involvement for the new apparatus established for colonial research after 1940. An understanding of the implications of the application of the research council system to the Colonial Empire requires engagement with the ideology promoted by the Agricultural Research Council (ARC) and Medical Research Council (MRC) which placed emphasis on the distinct and higher status of fundamental research and which privileged freedom for researchers.
doi:10.1017/mdh.2013.17
PMCID: PMC3865944  PMID: 24069883
Medical Research Council; Agricultural Research Council; Colonial Office; 1940 CDW Act; Colonial Medical Research Council; East Africa
21.  Application of the new GOLD COPD staging system to a US primary care cohort, with comparison to physician and patient impressions of severity 
Background
In 2011, the traditional Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPD spirometry-based severity classification system was revised to also include exacerbation history and COPD Assessment Test (CAT) and modified Medical Research Council Dyspnea Scale (mMRC) scores. This study examined how COPD patients treated in primary care are reclassified by the new GOLD system compared to the traditional system, and each system’s level of agreement with patient’s or physician’s severity assessments.
Methods
In this US multicenter cross-sectional study, COPD patients were recruited by 83 primary care practitioners (PCPs) to complete spirometry testing and a survey. Patients were classified by the traditional spirometry-based system (stages 1–4) and under the new system (grades A, B, C, D) using spirometry, exacerbation history, mMRC, and/or CAT results. Concordance between physician and patient-reported severity, spirometry stage, and ABCD grade based on either mMRC or CAT scores was examined.
Results
Data from 445 patients with spirometry-confirmed COPD were used. As compared to the traditional system, the GOLD mMRC system reclassifies 47% of patients, and GOLD CAT system reclassifies 41%, but the distributions are very different. The GOLD mMRC system resulted in relatively equal distributions by ABCD grade (33%, 22%, 19%, 26%, respectively), but the GOLD CAT system put most into either B or D groups (9%, 45%, 4%, and 42%). The addition of exacerbation history reclassified only 19 additional patients. Agreement between PCPs’ severity rating or their patients’ self-assessment and the new ABCD grade was very poor (κ=0.17 or less).
Conclusion
As compared to the traditional system, the GOLD 2011 multidimensional system reclassified nearly half of patients, but how they were reclassified varied greatly by whether the mMRC or CAT questionnaire was chosen. Either way, the new system had little correlation with the PCPs or their patients’ impressions about the COPD severity.
doi:10.2147/COPD.S78827
PMCID: PMC4524525  PMID: 26251587
assessment; comorbidity; exacerbation; Global Initiative for Chronic Obstructive Lung Disease; spirometry; stratification
22.  Epidemiological Pathology of Dementia: Attributable-Risks at Death in the Medical Research Council Cognitive Function and Ageing Study 
PLoS Medicine  2009;6(11):e1000180.
Researchers from the Medical Research Council Cognitive Function and Ageing Neuropathology Study carry out an analysis of brain pathologies contributing to dementia, within a cohort of elderly individuals in the UK who agreed to brain donation.
Background
Dementia drug development aims to modulate pathological processes that cause clinical syndromes. Population data (epidemiological neuropathology) will help to model and predict the potential impact of such therapies on dementia burden in older people. Presently this can only be explored through post mortem findings. We report the attributable risks (ARs) for dementia at death for common age-related degenerative and vascular pathologies, and other factors, in the MRC Cognitive Function and Ageing Study (MRC CFAS).
Methods and Findings
A multicentre, prospective, longitudinal study of older people in the UK was linked to a brain donation programme. Neuropathology of 456 consecutive brain donations assessed degenerative and vascular pathologies. Logistic regression modelling, with bootstrapping and sensitivity analyses, was used to estimate AR at death for dementia for specific pathologies and other factors. The main contributors to AR at death for dementia in MRC CFAS were age (18%), small brain (12%), neocortical neuritic plaques (8%) and neurofibrillary tangles (11%), small vessel disease (12%), multiple vascular pathologies (9%), and hippocampal atrophy (10%). Other significant factors include cerebral amyloid angiopathy (7%) and Lewy bodies (3%).
Conclusions
Such AR estimates cannot be derived from the living population; rather they estimate the relative contribution of specific pathologies to dementia at death. We found that multiple pathologies determine the overall burden of dementia. The impact of therapy targeted to a specific pathology may be profound when the dementia is relatively “pure,” but may be less impressive for the majority with mixed disease, and in terms of the population. These data justify a range of strategies, and combination therapies, to combat the degenerative and vascular determinants of cognitive decline and dementia.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Losing one's belongings and forgetting people's names is often a normal part of aging. But increasing forgetfulness can also be a sign of dementia, a group of symptoms caused by several disorders that affect the structure of the brain. The commonest form of dementia is Alzheimer disease. In this, protein clumps called plaques and neurofibrillary tangles form in the brain and cause its degeneration. Vascular dementia, in which problems with blood circulation deprive parts of the brain of oxygen, is also common. People with dementia have problems with two or more “cognitive” functions—thinking, language, memory, understanding, and judgment. As the disease progresses, they gradually lose their ability to deal with normal daily activities until they need total care, their personality often changes, and they may become agitated or aggressive. Dementia is rare before the age of 65 years but about a quarter of people over 85 years old have dementia. Because more people live to a ripe old age these days, the number of people with dementia is increasing. According to the latest estimates, about 35 million people now have dementia and by 2050, 115 million may have the disorder.
Why Was This Study Done?
There is no cure for dementia but many drugs designed to modulate specific abnormal (pathological) changes in the brain that can cause the symptoms of dementia are being developed. To assess the likely impact of these potentially expensive new therapies, experts need to know what proportion of dementia is associated with each type of brain pathology. Although some brain changes can be detected in living brains with techniques such as computed tomography brain scans, most brain changes can only be studied in brains taken from people after death (post mortem brains). In this study, which is part of the UK Medical Research Council Cognitive Function and Ageing Study (MRC CFAS), the researchers look for associations between dementia in elderly people and pathological changes in their post mortem brains and estimate the attributable-risk (AR) for dementia at death associated with specific pathological features in the brain. That is, they estimate the proportion of dementia directly attributable to each type of pathology.
What Did the Researchers Do and Find?
Nearly 20 years ago, the MRC CFAS interviewed more than 18,000 people aged 65 years or older recruited at six sites in England and Wales to determine their cognitive function and their ability to deal with daily activities. 20% of the participants, which included people with and without cognitive impairment, were then assessed in more detail and invited to donate their brains for post mortem examination. As of 2004, 456 individuals had donated their brains. The dementia status of these donors was established using data from their assessment interviews and death certificates, and from interviews with relatives and carers, and their brains were carefully examined for abnormal changes. The researchers then used statistical methods to estimate the AR for dementia at death associated with various abnormal brain changes. The main contributors to AR for dementia at death included age (18% of dementia at death was attributable to this factor), plaques (8%), and neurofibrillary tangles (11%) in a brain region called the neocortex, small blood vessel disease (12%), and multiple abnormal changes in blood vessels (9%).
What Do These Findings Mean?
These findings suggest that multiple abnormal brain changes determine the overall burden of dementia. Importantly, they also suggest that dementia is often associated with mixed pathological changes—many people with dementia had brain changes consistent with both Alzheimer disease and vascular dementia. Because people with dementia live for variable lengths of time during which the abnormal changes in their brain are likely to alter, it may be difficult to extrapolate these findings to living populations of elderly people. Furthermore, only a small percentage of the MRC CFAS participants have donated their brains so the findings of this study may not apply to the general population. Nevertheless, these findings suggest that the new therapies currently under development may do little to reduce the overall burden of dementia because most people's dementia involves multiple pathologies. Consequently, it may be necessary to develop a range of strategies and combination therapies to deal with the ongoing dementia epidemic.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000180.
The US National Institute on Aging provides information for patients and carers about forgetfulness and about Alzheimer disease (in English and Spanish)
The US National Institute of Neurological Disorders and Stroke provides information about dementia (in English and Spanish)
The UK National Health Service Choices Web site also provides detailed information for patients and their carers about dementia and about Alzheimer disease
MedlinePlus provides links to additional resources about dementia and Alzheimer disease (in English and Spanish)
More information about the UK Medical Research Council Cognitive Function and Ageing Study (MRC CFAS) is available
doi:10.1371/journal.pmed.1000180
PMCID: PMC2765638  PMID: 19901977
23.  Multipoint incremental motor unit number estimation versus amyotrophic lateral sclerosis functional rating scale and the medical research council sum score as an outcome measure in amyotrophic lateral sclerosis 
Introduction:
Monitoring the disease progression in amyotrophic lateral sclerosis (ALS) is a challenge due to different rates of progression between patients. Besides clinical methods to monitor disease progression, such as the ALS functional rating scale (ALSFRS) and the medical research council (MRC) sum score, quantitative methods like motor unit number estimation (MUNE) are of interest.
Objective:
The objective of the present study is to evaluate the rate of progression in ALS using multipoint incremental MUNE and to compare MUNE, ALSFRS and MRC sum score at baseline and at 6 months for progression of the disease.
Materials and Methods:
Multipoint incremental MUNE using median nerve, ALS-FRS and MRC sum score was carried out in 29 ALS patients at baseline and then at 6 months.
Results:
Of the 29 ALS patients studied, the mean MUNE at baseline was 21.80 (standard deviation [SD]: 19.46, range 4-73), 15.9 in the spinal onset group (SD: 14.60) and 30.16 (SD: 22.89) in the bulbar onset group. Spinal onset patients had 74.02% of baseline MUNE value while bulbar onset patients had only 24.74% baseline value MUNE at 6 months follow-up (Unpaired t-test, P = 0.001). ALSFRS and MRC sum score showed statistically significant decline (P < 0.001) at 6 months follow-up. MUNE had the highest sensitivity for progression of the disease when compared to the ALS FRS and MRC sum score.
Conclusion:
Multipoint incremental MUNE is a valuable tool for outcome measure in ALS and other diseases characterized by motor unit loss. The rate of decline of multipoint incremental MUNE is more sensitive than that of MRC sum score and ALSFRS-R, when expressed as the percentage change from baseline.
doi:10.4103/0972-2327.138522
PMCID: PMC4162024  PMID: 25221407
Amyotrophic lateral sclerosis functional rating scale; amyotrophic lateral sclerosis; compound muscle action potential; medical research council sum score; motor unit estimation; single motor unit action potential amplitude
24.  External Validation and Recalibration of Risk Prediction Models for Acute Traumatic Brain Injury among Critically Ill Adult Patients in the United Kingdom 
Journal of Neurotrauma  2015;32(19):1522-1537.
Abstract
This study validates risk prediction models for acute traumatic brain injury (TBI) in critical care units in the United Kingdom and recalibrates the models to this population. The Risk Adjustment In Neurocritical care (RAIN) Study was a prospective, observational cohort study in 67 adult critical care units. Adult patients admitted to critical care following acute TBI with a last pre-sedation Glasgow Coma Scale score of less than 15 were recruited. The primary outcomes were mortality and unfavorable outcome (death or severe disability, assessed using the Extended Glasgow Outcome Scale) at six months following TBI. Of 3626 critical care unit admissions, 2975 were analyzed. Following imputation of missing outcomes, mortality at six months was 25.7% and unfavorable outcome 57.4%. Ten risk prediction models were validated from Hukkelhoven and colleagues, the Medical Research Council (MRC) Corticosteroid Randomisation After Significant Head Injury (CRASH) Trial Collaborators, and the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) group. The model with the best discrimination was the IMPACT “Lab” model (C index, 0.779 for mortality and 0.713 for unfavorable outcome). This model was well calibrated for mortality at six months but substantially under-predicted the risk of unfavorable outcome. Recalibration of the models resulted in small improvements in discrimination and excellent calibration for all models. The risk prediction models demonstrated sufficient statistical performance to support their use in research and audit but fell below the level required to guide individual patient decision-making. The published models for unfavorable outcome at six months had poor calibration in the UK critical care setting and the models recalibrated to this setting should be used in future research.
doi:10.1089/neu.2014.3628
PMCID: PMC4589267  PMID: 25898072
outcome measures; prospective study; traumatic brain injury
25.  Can Motor Evoked Potentials Be an Objective Parameter to Assess Extremity Function at the Acute or Subacute Stroke Stage? 
Annals of Rehabilitation Medicine  2015;39(2):253-261.
Objective
To investigate whether motor evoked potential (MEP) amplitude ratio measurements are sufficiently objective to assess functional activities of the extremities. We also delineated the distribution between the presence or absence of MEPs and the Medical Research Council (MRC) scale for muscle strength of the extremities.
Methods
We enrolled 183 patients with first-ever unilateral hemiplegia after stroke. The MEP parameters were amplitude ratio (amplitude of affected side/amplitude of unaffected side) recorded at the first dorsal interosseous (FDI) and tibialis anterior (TA) muscles. We performed frequency analyses using the MRC scale for muscle strength and the presence or absence of evoked MEPs. Change on the MRC scale, hand function tests (HFTs), and the Modified Barthel Index (MBI) subscore were compared between the evoked MEP and absent MEP groups using the independent t-test. Receiver operating characteristic curves were used to determine the optimal cutoff scores for the MEP amplitude ratio using the HFT results and MBI subscores. Correlations between the MEP amplitude ratio and the MRC scale, HFTs, and MBI subscore were analyzed.
Results
About 10% of patients with MRC scale grades 0-2 showed evoked MEPs at the FDI muscle, and 4% of patients with MRC scale grades 3-5 did not show MEPs. About 18% of patients with MRC scale grades 0-2 showed evoked MEPs at the TA muscle, and 4% of patients with MRC scale grades 3-5 did not show MEPs. MEP amplitude increased with increasing MRC scale grade. The evoked MEP group had more significant changes on the MRC scale, HFT, and the climbing stair score on the MBI than those in the group without MEPs. Larger MEP amplitude ratios were observed in patients who had more difficulty with the HFTs and ambulation. The MEP amplitude ratio was significantly correlated with the MRC scale, HFT, and MBI subscore.
Conclusion
We conclude that the MEP amplitude ratio may be useful to predict functional status of the extremities in patients who suffered stroke.
doi:10.5535/arm.2015.39.2.253
PMCID: PMC4414972  PMID: 25932422
Motor evoked potentials; Muscle strength; Activities of daily living; Motor skills; Stroke

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