Challenges in Providing Timely Physiotherapy and Opportunities to Influence Outcomes for Potential Lung Donors.

CONTEXT: There is a critical shortage of donor lungs however, considerable ethical considerations are associated with the conduct of research to optimize care of the potential organ donor. OBJECTIVE: To investigate pathways of consent, respiratory care by physiotherapists and donation rates to contextualize future research on physiotherapy effects on donor lung suitability for procurement. DESIGN: Retrospective audit. SETTING: Australian tertiary hospital. PATIENTS: Potential organ donors (defined as patients who may have been eligible to donate organs for transplantation via either brain death or circulatory death) 75 years or younger presenting to the emergency department or the intensive care unit (ICU) between September 2011 and December 2012. MAIN OUTCOME MEASURES: Donation rates, timing of organ procurement from initial hospital presentation, number of persons designated to make health-care decisions approached for and consenting to donation and clinical research, and number of patients assessed and/or treated by physiotherapists. RESULTS: Records of 65 potentially eligible donors were analyzed. Eighteen (28%) of the 65 became donors. Organ procurement occurred at a median of 48 hours (interquartile range: 34-72 hours) after ICU admission. All decision-makers approached regarding participation in clinical research (4 [6%] of the 65) consented. Physiotherapists assessed 48 (74%) of the 65 patients at least once and provided 28 respiratory treatments to 18 (28%) of the 65 patients, including lung hyperinflation and positioning. Limitations were the retrospective, single-center design and the "potential organ donor" definition. CONCLUSION: Organ procurement occurs early. There is potential for early intervention to improve lung donor rates. Randomized controlled trials investigating protocolized respiratory packages of care may increase the potential donor pool and transplantation rates.

How Physically Active Are People Following Stroke? Systematic Review and Quantitative Synthesis.

BACKGROUND: Mobility limitations are common following stroke and frequently lead to poor participation in physical activity (PA). PURPOSE: The purpose of this study was to describe PA across the various stages following stroke (acute, subacute, and chronic). DATA SOURCES: Searches were conducted in 5 databases. STUDY SELECTION: Eligible studies included participants with stroke whose PA was quantitatively measured for at least 4 hours in a single session. Two reviewers independently reviewed titles and abstracts. DATA EXTRACTION: One reviewer extracted data and assessed quality using the Downs and Black checklist. Weighted means were calculated for PA outcomes. DATA SYNTHESIS: Searches yielded 103 eligible papers including 5306 participants aged 21 to 96 years. Devices (eg, activity monitors) were used in 73 papers, and behavioral mapping (observational monitoring) in 30. Devices show that people with stroke took on average 5535 steps per day (n = 406, 10 studies) in the subacute phase and 4078 steps (n = 1280, 32 studies) in the chronic phase. Average daily walking duration (% measured time) was higher in the chronic phase (9.0%, n = 100) than subacute (1.8%, n = 172), and sedentary time was >78% regardless of time post stroke. Acute data were lacking for these variables. Matched healthy individuals took an average of 8338 steps per day (n = 129). Behavioral mapping showed time in bed was higher in the acute than subacute phase (mean 45.1% versus 23.8%), with similar time spent sitting (mean 37.6% versus 32.6%). LIMITATIONS: Limitations of this review include not pooling data reported as medians. CONCLUSIONS: Physical activity levels do not meet guidelines following stroke. Time spent inactive and sedentary is high at all times. Increasing PA and developing standardized activity targets may be important across all stages of stroke recovery.

Peer-Assisted Learning in Education of Allied Health Professional Students in the Clinical Setting: A Systematic Review.

Pressure on clinical educators to provide best practice education to growing student numbers is driving innovations in clinical education. Placing multiple students with a single clinical educator may increase capacity; however, little is known about the role and impact of peer-assisted learning (PAL) in these models. A systematic review of the literature from 1985 to 2014 was done to investigate the effectiveness of PAL amongst allied health professional students in clinical settings. Secondary aims were to investigate how PAL is defined and measured in this practice setting. Twenty-eight articles representing five allied health professions met the inclusion criteria. The risk of bias in the articles was generally high, limiting confidence in findings. Nine studies measured the effects of PAL on students, with inconsistent results across domains of satisfaction, perceived learning, and performance outcomes. Only four studies described how PAL was facilitated. Evidence supporting PAL is non-specific and lacks comparative rigour. More robust research is needed to quantify the potential benefits of PAL.

Simulated Patients in Physical Therapy Education: Systematic Review and Meta-Analysis.

BACKGROUND: Traditional models of physical therapy clinical education are experiencing unprecedented pressures. Simulation-based education with simulated (standardized) patients (SPs) is one alternative that has significant potential value, and implementation is increasing globally. However, no review evaluating the effects of SPs on professional (entry-level) physical therapy education is available. PURPOSE: The purpose of this study was to synthesize and critically appraise the findings of empirical studies evaluating the contribution of SPs to entry-level physical therapy education, compared with no SP interaction or an alternative education strategy, on any outcome relevant to learning. DATA SOURCES: A systematic search was conducted of Ovid MEDLINE, PubMed, AMED, ERIC, and CINAHL Plus databases and reference lists of included articles, relevant reviews, and gray literature up to May 2015. STUDY SELECTION: Articles reporting quantitative or qualitative data evaluating the contribution of SPs to entry-level physical therapy education were included. DATA EXTRACTION: Two reviewers independently extracted study characteristics, intervention details, and quantitative and qualitative evaluation data from the 14 articles that met the eligibility criteria. DATA SYNTHESIS: Pooled random-effects meta-analysis indicated that replacing up to 25% of authentic patient-based physical therapist practice with SP-based education results in comparable competency (mean difference=1.55/100; 95% confidence interval=-1.08, 4.18; P=.25). Thematic analysis of qualitative data indicated that students value learning with SPs. LIMITATIONS: Assumptions were made to enable pooling of data, and the search strategy was limited to English. CONCLUSION: Simulated patients appear to have an effect comparable to that of alternative educational strategies on development of physical therapy clinical practice competencies and serve a valuable role in entry-level physical therapy education. However, available research lacks the rigor required for confidence in findings. Given the potential advantages for students, high-quality studies that include an economic analysis should be conducted.

Remote-online case-based learning: A comparison of remote-online and face-to-face, case-based learning - a randomized controlled trial.

BACKGROUND: Case-based learning (CBL) is an educational approach where students work in small, collaborative groups to solve problems. Computer assisted learning (CAL) is the implementation of computer technology in education. The purpose of this study was to compare the effects of a remote-online CBL (RO-CBL) with traditional face-to-face CBL on learning the outcomes of undergraduate physiotherapy students. METHODS: Participants were randomized to either the control (face-to-face CBL) or to the CAL intervention (RO-CBL). The entire 3rd year physiotherapy cohort (n = 41) at Monash University, Victoria, Australia, were invited to participate in the randomized controlled trial. Outcomes included a postintervention multiple-choice test evaluating the knowledge gained from the CBL, a self-assessment of learning based on examinable learning objectives and student satisfaction with the CBL. In addition, a focus group was conducted investigating perceptions and responses to the online format. RESULTS: Thirty-eight students (control n = 19, intervention n = 19) participated in two CBL sessions and completed the outcome assessments. CBL median scores for the postintervention multiple-choice test were comparable (Wilcoxon rank sum P = 0.61) (median/10 [range] intervention group: 9 [8-10] control group: 10 [7-10]). Of the 15 examinable learning objectives, eight were significantly in favor of the control group, suggesting a greater perceived depth of learning. Eighty-four percent of students (16/19) disagreed with the statement "I enjoyed the method of CBL delivery." Key themes identified from the focus group included risks associated with the implementation of, challenges of communicating in, and flexibility offered, by web-based programs. DISCUSSION: RO-CBL appears to provide students with a comparable learning experience to traditional CBL. Procedural and infrastructure factors need to be addressed in future studies to counter student dissatisfaction and decreased perceived depth of learning.

How is physical activity monitored in people following stroke?

PURPOSE: To describe how physical activity is monitored following stroke; to summarise methods and devices used across the stroke pathway and document their psychometric properties. METHODS: Searches of five databases identified studies that included stroke survivors whose physical activity was quantitatively measured. Two reviewers independently determined inclusion. A descriptive synthesis was undertaken and reliability data for specific methods of monitoring physical activity were pooled where possible. RESULTS: Ninety-one papers (60 using devices and 31 using observational methods) met inclusion criteria, with 3479 participants aged 21-96 years. Twenty-nine devices (72% accelerometers) were identified. Devices were typically used to measure ambulant participants more than 6 months following stroke. Direct observation of physical activity was commonly used for inpatients. No outcome measurements were common to all methods/devices. Test-retest reliability was not reported for 23 devices; for the remaining six it ranged from r = 0.44 to r = 0.99. Inter-rater reliability of observational methods ranged from 0.51 to 1.0. Validity was infrequently reported. CONCLUSIONS: Physical activity outcomes were variable. Devices allow for unobtrusive, sustained monitoring in free-living environments. Observational methods suit inpatient settings but are time and labour intensive. No single approach appears superior but standardisation of outcomes would improve the field. IMPLICATIONS FOR REHABILITATION: Physical activity measurement is highly variable following stroke and better definition of physical activity outcomes would enhance the field. Accelerometry and behavioural mapping are most commonly used to measure physical activity following stroke, each have advantages and disadvantages depending on the setting and the outcome of interest. There is no single device ideal for clinical application for people following stroke.

The concurrent validity of brief screening questions for anxiety, depression, social isolation, catastrophization, and fear of movement in people with low back pain.

OBJECTIVES: The aim of this study was to (1) test the concurrent validity of brief screening questions for 5 psychosocial constructs (anxiety, depression, social isolation, catastrophization, and fear of movement) and (2) translate into Danish and validate those screening questions. MATERIALS AND METHODS: Data were collected from 5 cross-sectional samples (total n=1105) of people seeking care for low back pain in Australian primary care settings and a Danish secondary care hospital. The responses to English and Danish-translated versions of 1-item or 2-item screening questions were compared with those of validated full-length questionnaires. RESULTS: Compared with anxiety, depression, and social isolation scores from full-length questionnaires, screening questionnaire responses demonstrated: a correlation of 0.62 to 0.83, overall accuracy of 78% to 91%, sensitivity of 70% to 82%, specificity of 75% to 95%, positive likelihood ratios of 3.3 to 13.9, and negative likelihood ratios of 0.21 to 0.33. For catastrophization and fear of movement, the results demonstrated: correlation of 0.89 to 0.95, overall accuracy of 88% to 93%, sensitivity of 78% to 88%, specificity of 91% to 96%, positive likelihood ratios of 9.5 to 20.8, and negative likelihood ratios of 0.13 to 0.23. DISCUSSION: The concurrent validity of these screening questions was comparable to, or better than, alternate questions previously reported, and stable across age, sex, pain intensity, pain duration, and counties. On the basis of the observed likelihood ratios, all of the screening questions provided moderate or strong evidence to rule in or out an extreme score on each psychosocial construct. Given the ease of administration of these brief screening questions, their prognostic and treatment implications should be investigated.

Breakeven, cost benefit, cost effectiveness, and willingness to pay for web-based versus face-to-face education delivery for health professionals.

BACKGROUND: The introduction of Web-based education and open universities has seen an increase in access to professional development within the health professional education marketplace. Economic efficiencies of Web-based education and traditional face-to-face educational approaches have not been compared under randomized controlled trial conditions. OBJECTIVE: To compare costs and effects of Web-based and face-to-face short courses in falls prevention education for health professionals. METHODS: We designed two short courses to improve the clinical performance of health professionals in exercise prescription for falls prevention. One was developed for delivery in face-to-face mode and the other for online learning. Data were collected on learning outcomes including participation, satisfaction, knowledge acquisition, and change in practice, and combined with costs, savings, and benefits, to enable a break-even analysis from the perspective of the provider, cost-effectiveness analysis from the perspective of the health service, and cost-benefit analysis from the perspective of the participant. RESULTS: Face-to-face and Web-based delivery modalities produced comparable outcomes for participation, satisfaction, knowledge acquisition, and change in practice. Break-even analysis identified the Web-based educational approach to be robustly superior to face-to-face education, requiring a lower number of enrollments for the program to reach its break-even point. Cost-effectiveness analyses from the perspective of the health service and cost-benefit analysis from the perspective of the participant favored face-to-face education, although the outcomes were contingent on the sensitivity analysis applied (eg, the fee structure used). CONCLUSIONS: The Web-based educational approach was clearly more efficient from the perspective of the education provider. In the presence of relatively equivocal results for comparisons from other stakeholder perspectives, it is likely that providers would prefer to deliver education via a Web-based medium. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN): 12610000135011; http://www.anzctr.org.au/trial_view.aspx?id=335135 (Archived by WebCite at http://www.webcitation.org/668POww4L).

Management of people with acute low-back pain: a survey of Australian chiropractors.

INTRODUCTION: Chiropractors commonly provide care to people with acute low-back pain (LBP). The aim of this survey was to determine how chiropractors intend to support and manage people with acute LBP and if this management is in accordance with two recommendations from an Australian evidence-based acute LBP guideline. The two recommendations were directed at minimising the use of plain x-ray and encouraging the patient to stay active. METHODS: This is a cross sectional survey of chiropractors in Australia. This paper is part of the ALIGN study in which a targeted implementation strategy was developed to improve the management of acute LBP in a chiropractic setting. This implementation strategy was subsequently tested in a cluster randomised controlled trial. In this survey phase of the ALIGN study we approached a random sample of 880 chiropractors in three States of Australia. The mailed questionnaire consisted of five patient vignettes designed to represent people who would typically present to chiropractors with acute LBP. Four vignettes represented people who, according to the guideline, would not require a plain lumbar x-ray, and one vignette represented a person with a suspected vertebral fracture. Respondents were asked, for each vignette, to indicate which investigation(s) they would order, and which intervention(s) they would recommend or undertake. RESULTS: Of the 880 chiropractors approached, 137 were deemed ineligible to participate, mostly because they were not currently practising, or mail was returned to sender. We received completed questionnaires from 274 chiropractors (response rate of 37%). Male chiropractors made up 66% of respondents, 75% practised in an urban location and their mean number of years in practice was 15. Across the four vignettes where an x-ray was not indicated 68% (95% Confidence Intervals (CI): 64%, 71%) of chiropractors responded that they would order or take an x-ray. In addition 51% (95%CI: 47%, 56%) indicated they would give advice to stay active when it was indicated. For the vignette where a fracture was suspected, 95% (95% CI: 91%, 97%) of chiropractors would order an x-ray. CONCLUSION: The intention of chiropractors surveyed in this study shows low adherence to two recommendations from an evidence-based guideline for acute LBP. Quality of care for these patients could be improved through effective implementation of evidence-based guidelines. Further research to find cost-effective methods to increase implementation is warranted.

The Assessment of Physiotherapy Practice (APP) is a valid measure of professional competence of physiotherapy students: a cross-sectional study with Rasch analysis.

QUESTION: Is the Assessment of Physiotherapy Practice (APP) a valid instrument for the assessment of entry-level competence in physiotherapy students? DESIGN: Cross-sectional study with Rasch analysis of initial (n=326) and validation samples (n=318). Students were assessed on completion of 4, 5, or 6-week clinical placements across one university semester. PARTICIPANTS: 298 clinical educators and 456 physiotherapy students at nine universities in Australia and New Zealand provided 644 completed APP instruments. RESULTS: APP data in both samples showed overall fit to a Rasch model of expected item functioning for interval scale measurement. Item 6 (Written communication) exhibited misfit in both samples, but was retained as an important element of competence. The hierarchy of item difficulty was the same in both samples with items related to professional behaviour and communication the easiest to achieve and items related to clinical reasoning the most difficult. Item difficulty was well targeted to person ability. No Differential Item Functioning was identified, indicating that the scale performed in a comparable way regardless of the student's age, gender or amount of prior clinical experience, and the educator's age, gender, or experience as an educator, or the type of facility, university, or clinical area. The instrument demonstrated unidimensionality confirming the appropriateness of summing the scale scores on each item to provide an overall score of clinical competence and was able to discriminate four levels of professional competence (Person Separation Index=0.96). Person ability and raw APP scores had a linear relationship (r(2)=0.99). CONCLUSION: Rasch analysis supports the interpretation that a student's APP score is an indication of their underlying level of professional competence in workplace practice.

A randomised controlled trial of an open lung strategy with staircase recruitment, titrated PEEP and targeted low airway pressures in patients with acute respiratory distress syndrome.

INTRODUCTION: Tidal volume and plateau pressure minimisation are the standard components of a protective lung ventilation strategy for patients with acute respiratory distress syndrome (ARDS). Open lung strategies, including higher positive end-expiratory pressure (PEEP) and recruitment manoeuvres to date have not proven efficacious. This study examines the effectiveness and safety of a novel open lung strategy, which includes permissive hypercapnia, staircase recruitment manoeuvres (SRM) and low airway pressure with PEEP titration. METHOD: Twenty ARDS patients were randomised to treatment or ARDSnet control ventilation strategies. The treatment group received SRM with decremental PEEP titration and targeted plateau pressure < 30 cm H2O. Gas exchange and lung compliance were measured daily for 7 days and plasma cytokines in the first 24 hours and on days 1, 3, 5 and 7 (mean ± SE). Duration of ventilation, ICU stay and hospital stay (median and interquartile range) and hospital survival were determined. RESULTS: There were significant overall differences between groups when considering plasma IL-8 and TNF-α. For plasma IL-8, the control group was 41% higher than the treatment group over the seven-day period (ratio 1.41 (1.11 to 1.79), P = 0.01), while for TNF-α the control group was 20% higher over the seven-day period (ratio 1.20 (1.01 to 1.42) P = 0.05). PaO2/FIO2 (204 ± 9 versus 165 ± 9 mmHg, P = 0.005) and static lung compliance (49.1 ± 2.9 versus 33.7 ± 2.7 mls/cm H2O, P < 0.001) were higher in the treatment group than the control group over seven days. There was no difference in duration of ventilation (180 (87 to 298) versus 341 (131 to 351) hrs, P = 0.13), duration of ICU stay (9.9 (5.6 to 14.8) versus 16.0 (8.1 to 19.3) days, P = 0.19) and duration of hospital stay (17.9 (13.7 to 34.5) versus 24.7 (20.5 to 39.8) days, P = 0.16) between the treatment and control groups. CONCLUSIONS: This open lung strategy was associated with greater amelioration in some systemic cytokines, improved oxygenation and lung compliance over seven days. A larger trial powered to examine clinically-meaningful outcomes is warranted. TRIAL REGISTRATION: ACTRN12607000465459.

A positive response to a recruitment maneuver with PEEP titration in patients with ARDS, regardless of transient oxygen desaturation during the maneuver.

UNLABELLED: Recruitment maneuvers (RMs) can expand collapsed alveoli in ventilated patients. The optimal method for delivering RMs is unknown. PURPOSE: To evaluate the safety and the respiratory and hemodynamic effects of a staircase recruitment maneuver (SRM) with decremental positive end expiratory pressure (PEEP) titration and the consequences of desaturation during the SRM in patients with early acute lung injury (ALI). METHODS: In total, 20 consecutive patients with early ALI were enrolled and received an SRM. Patients were given 15 ± 3 cm H(2)O pressure-controlled ventilation. Positive end expiratory pressure was increased from baseline (range 10-18) to 20, 30, and 40 cm H(2)O every 2 minutes to achieve maximum alveolar pressure of 55 ± 3 cm H(2)O, then decreased at 3-minute intervals to 25, 22.5, 20, 17.5, and 15 cm H(2)O until a decrease of 1% to 2% oxygen saturation from maximum was detected. Positive end expiratory pressure was left at the level where the fall in oxygen saturation occurred. Standard respiratory and circulatory variables, arterial and central venous gases were measured before, during, and after the SRM. RESULTS: There were significant improvements in shunt fraction (36.3% ± 10% to 26.4% ± 14%, P < .001), oxygen saturation (93.4% ± 2% to 96.8% ± 3%, P = .007), partial pressure of oxygen, arterial (PaO(2))/fraction of inspired oxygen ([FIO(2)]; 150 ± 42 to 227 ± 100, P = .004), lung compliance (33.9 ± 9.1 to 40.1 ± 11.4 mL/cm H(2)O, P < .01), and chest x-ray (CXR) after the SRM. Briefly, 80% of the patients responded and the response was maintained at 1 hour. In total, 8 patients desaturated 6.1% ± 2.8% in SaO(2) during the SRM but 5 of those improved SaO(2) relative to baseline by the end of the SRM. CONCLUSIONS: In all, 80% of the patients with early ALI responded to the SRM with decremental PEEP titration. Desaturation during the SRM did not indicate a failed response 1 hour later.

The Interaction with Disabled Persons scale: revisiting its internal consistency and factor structure, and examining item-level properties.

The Interaction with Disabled Persons scale (IDP) has been used in research into baseline attitudes and to evaluate whether a shift in attitudes towards people with developmental disabilities has occurred following some form of intervention. This research has been conducted on the assumption that the IDP measures attitudes as a multidimensional construct and has good internal consistency. Such assumptions about the IDP appear flawed, particularly in light of failures to replicate its underlying factor structure. The aim of this study was to evaluate the construct validity and dimensionality of the IDP. This study used a prospective survey approach. Participants were recruited from first and second year undergraduate university students enrolled in health sciences, occupational therapy, physiotherapy, community and emergency health, nursing, and combined degrees of nursing and midwifery, and health sciences and social work at a large Australian university (n=373). Students completed the IDP, a 20-item self-report scale of attitudes towards people with disabilities. The IDP data were analysed using a combination of factor analysis (Classical Test Theory approach) and Rasch analysis (Item Response Theory approach). The results indicated that the original IDP 6-factor solution was not supported. Instead, one factor consisting of five IDP items (9, 11, 12, 17, and 18) labelled Discomfort met the four criteria for empirical validation of test quality: interval level scaling (scalability), unidimensionality, lacked of DIF across the two participant groups and data collection occasions, and hierarchical ordering. Researchers should consider using the Discomfort subscale of the IDP in future attitude research since it exhibits sound measurement properties.

Does clinician treatment choice improve the outcomes of manual therapy for nonspecific low back pain? A metaanalysis.

OBJECTIVE: The purpose of this study is to quantitatively compare outcomes for trials when treating clinicians did, or did not, have the discretion to decide on treatment technique. METHODS: CINAHL, EMBASE, MEDLINE, the Physiotherapy Evidence Database, the Cochrane Controlled Trials register, reference list searching, and citation tracking were investigated. Ten randomized controlled trials (RCTs) of mobilization and manipulation for nonspecific low back pain (NSLBP) met the inclusion criteria. The effectiveness of manual therapy with and without clinician technique choice was assessed using descriptive statistics and metaanalysis for the outcomes of pain and activity limitation. RESULTS: In approximately two thirds of the included RCTs, clinicians had choice of treatment technique. There were no systematic differences favoring results for RCTs that did allow clinician choice of treatment technique. CONCLUSIONS: Few quality studies are available, and conclusions on the basis of these data need to be interpreted with caution. However, allowing clinicians to choose from a number of treatment techniques does not appear to have improved the outcomes of these RCTs that have investigated the effect of manual therapy for NSLBP. If tailoring manual therapy treatment to NSLBP patients does positively impact on patient outcomes, this is not yet systematically apparent.

Do primary-care clinicians think that nonspecific low back pain is one condition?

STUDY DESIGN: Postal survey. OBJECTIVES.: To determine whether Australian primary-care clinicians think that nonspecific low back pain (NSLBP) is one condition or a number of conditions (subgroups), and whether this belief influences their management of NSLBP. SUMMARY OF BACKGROUND DATA: Most low back pain (LBP) remains a diagnostic enigma and results in approximately 80% of primary care LBP presentations being most accurately labeled as "nonspecific LBP." Manual therapy clinicians (chiropractors, osteopaths, physiotherapists) are trained to think that subgroups exist within the NSLBP population. This research sought to identify the extent to which these beliefs are widely held in primary care. METHODS: A survey was conducted of 1,093 primary-contact clinicians from six professional disciplines (physiotherapists, manipulative physiotherapists, chiropractors, osteopaths, general medical practitioners, and musculoskeletal medicine practitioners). RESULTS: Completed questionnaires were returned by 651 (60%) clinicians. Of the primary-contact clinicians who responded, 93% do not think NSLBP is one condition. Seventy-four percent think that it is currently possible to recognize NSLBP subgroups. Ninety-three percent treat NSLBP differently based on patterns of signs and symptoms. The proportions of clinicians who hold these views were highest for physiotherapists and manipulative physiotherapists, and smallest for general medical practitioners and musculoskeletal medicine practitioners. CONCLUSIONS: Although assigning NSLBP patients to subgroups has not been validated, it is common in primary-care settings and influences case management. If subgroups exist within the NSLBP population, there are implications for research into the effects of treatment. Further research into the validity of subgroups is warranted.