The Association of Health Locus of Control with Clinical and Psychosocial Aspects of Living with Multiple Sclerosis.

Health Locus of control (LOC) refers to one's beliefs regarding control over one's health. This study aimed to determine the relationship between LOC on clinical and psychosocial aspects associated with multiple sclerosis (MS). 5059 participants with MS completed a questionnaire pack including the Multidimensional Health Locus of Control Scale. Associations between LOC and sociodemographic (age, gender, educational level) and clinical variables (duration, disability, depression, anxiety, self-efficacy, QoL) were explored. LOC was found to be significantly associated with all of the clinical variables and age, but not gender or educational level. When controlling for level of disability, Chance (CLOC) was associated with higher self-efficacy, lower anxiety and higher QoL than Powerful Others (PLOC), while Internal (ILOC) had no association. The proportion with ILOC preference was lower in increased disability. In MS, believing that health is controlled mainly by chance confers the most benefit with regard to quality of life. There is prima-facie evidence that LOC preference changes with MS progression, in a pattern that is protective against psychological distress.

Prevalence of depression in amyotrophic lateral sclerosis/motor neuron disease: multi-attribute ascertainment and trajectories over 30 months.

Objective: Evidence is equivocal about the prevalence of depression in amyotrophic lateral sclerosis (ALS). This study uses a multi-attribute ascertainment of the prevalence of depression and examines this prevalence over time. Methods: Patients with ALS were recruited into the Trajectories of Outcome in Neurological Conditions (TONiC-ALS) study. Caseness was identified by the Modified-Hospital Anxiety and Depression Scale (M-HADS). In addition, participants provided data on co-morbidities and medication use. A combination of the three was used to derive the estimate for the prevalence of depression, treated or untreated. Longitudinal data were analyzed by trajectory analysis of interval level M-HADS-Depression data. Results: Among 1120 participants, the mean age was 65.0 years (SD 10.7), 60.4% male, and the median duration since diagnosis was 9 months (IQR 4-24). Caseness of probable depression at baseline, defined by M-HADS-Depression, was 6.45% (95%CI: 5.1-8.0). Taken together with antidepressant medication and co-morbidity data, the prevalence of depression was 23.1% (95%CI: 20.7-25.6). Of those with depression, 17.8% were untreated. Trajectory analysis identified three groups, one of which contained the most cases; the level of depression for each group remained almost constant over time. Conclusion: Depression affects almost a quarter of those with ALS, largely confined to a single trajectory group. Prevalence estimates based on screening for current depressive symptoms substantially under-estimate the population experiencing depression. Future prevalence studies should differentiate data based on current symptoms from those including treated patients. Both have their place in assessing depression and the response by the health care system, including medication, depending upon the hypothesis under test.

Measuring coping in people with amyotrophic lateral sclerosis using the Coping Index-ALS: A patient derived, Rasch compliant scale.

OBJECTIVE: The progressively disabling and terminal nature of ALS/MND imposes major coping demands on patients. We wished to improve the psychometric properties of our previously published MND-Coping Scale, so that parametric analyses were valid, and to make it simpler for patients to complete and clinicians to score. METHODS: After a new qualitative analysis of 26 patients with ALS/MND, the draft Coping Index-ALS (CI-ALS) was administered to 465 additional patients, alongside COPE-60, General Perceived Self Efficacy scale, and WHOQOL-BREF. Validity of the CI-ALS was assessed using the Rasch model. External validity was checked against comparator measures. RESULTS: Thirteen centres contributed 465 patients, mean age 64.9 years (SD 10.8), mean disease duration 28.4 months (SD 37.5). The CI-ALS-Self and CI-ALS-Others both satisfied Rasch model expectations and showed invariance across age, gender, marital status and type of onset. Expected correlations were observed with comparator scales. A nomogram is available to convert the raw scores to interval level measures suitable for parametric analysis. CONCLUSIONS: Coping abilities in ALS/MND can now be measured using a simple 21 item self-report measure, offering two subscales with a focus of 'coping by self ' and 'coping with others'. This allows clinicians to identify individuals with poor coping and facilitates research on interventions that may improve coping skills.

The WHOQOL-BREF: a modern psychometric evaluation of its internal construct validity in people with multiple sclerosis.

PURPOSE: Symptoms of Multiple Sclerosis (MS) differentially impact upon quality of life (QoL) and a comprehensive measure is required for use in observational and interventional studies. This study examines the abbreviated World Health Organisation Quality of Life tool (WHOQOL-BREF) which was designed to be used as a broad measure of QoL across different cultures and diseases. METHODS: Data were collected from 3186 subjects as part of the TONiC study in MS and was examined with a systematic, iterative approach using Rasch analysis to investigate the internal construct validity of the WHOQOL-BREF. RESULTS: Mean age was 49.8 years (SD 11.8), disease duration was 11.2 years (SD 9.6) and 73.2% were female. Subjects represented all stages of MS with EDSS scores of 0-4, 4.5-6.5, 7-7.5 and ≥ 8 seen in 49.8%, 38.5%, 6.8% and 4.9% of patients, respectively. Using a super-item approach, it was possible to demonstrate fit to the assumptions of the Rasch model for 3 of the 4 domains of the WHOQOL-BREF (physical, psychological and environment) as well as a broad 24-item total score. In addition, item subsets derived from the stem of each question were shown to function as novel scales measuring impact and life satisfaction. We have provided transformation tables from ordinal raw scores to interval scales where data are complete. CONCLUSIONS: The validation of multiple conceptual frameworks validates the WHOQOL-BREF as a powerful and flexible end-point for use in clinical trials and in testing conceptual models of factors influencing QoL in MS.

Use of coping strategies in multiple sclerosis: Association with demographic and disease-related characteristics✰.

BACKGROUND: Coping positively and negatively influences psychosocial and other outcomes in multiple sclerosis (MS), but there is conflicting evidence about the use of different coping strategies and their associations with demographic and disease characteristics. Our aims were to examine which coping strategies are used by a large sample of people with MS, then to identify any associations between demographic and disease related factors with use of individual coping strategies. METHODS: Participants in the Trajectories of Outcomes in Neurological Conditions (TONiC) study completed the Coping Orientations to Problems Experienced (COPE60) questionnaire. Relationships between demographic and clinical characteristics and coping strategies were examined by multiple ordinal logistic regression to assess the effect of each potential predictor after adjustment for other possible covariates. RESULTS: From 722 patients, the most commonly used strategy was Acceptance, followed by Active Coping, Planning and Positive Reinterpretation and Growth. All but two strategies showed significant associations with demographic and clinical characteristics. The most marked effects were found for Restraint, with people in employment 2.1 times as likely to utilise this strategy compared to those unemployed, and Seeking of Emotional Social Support and Focus on and Venting of Emotions, which were utilised twice as much by women compared to men. Behavioural and Mental Disengagement were highly associated with greater disability and not being in employment. CONCLUSION: Clinicians should be aware of several disease and demographic characteristics that are associated with use of potentially maladaptive coping strategies.

Development and validation of Spasticity Index-Amyotrophic Lateral Sclerosis.

OBJECTIVES: Spasticity is a common and disabling feature of amyotrophic lateral sclerosis (ALS). There are currently no validated ALS-specific measures of spasticity. The aim of this study was to develop and use a self-report outcome measure for spasticity in ALS. METHODS: Following semi-structured interviews with 11 ALS patients, a draft scale was administered across ALS clinics in the UK. Internal validity of the scale was examined using the Rasch model. The numerical rating scale (NRS) for spasticity and Leeds Spasticity scale (LSS) were co-administered. The final scale was used in a path model of spasticity and quality of life. RESULTS: A total of 465 patients (mean age 64.7 years (SD 10), 59% male) with ALS participated. Spasticity was reported by 80% of subjects. A pool of 71 items representing main themes of physical symptoms, negative impact and modifying factors was subject to an iterative process of item reduction by Rasch analysis resulting in a 20-item scale-the Spasticity Index for ALS (SI-ALS)-which was unidimensional and free from differential item functioning. Moderate correlations were found with LSS and NRS-spasticity. Incorporating the latent estimate of spasticity into a path model, greater spasticity reduced quality of life and motor function; higher motor function was associated with better quality of life. CONCLUSIONS: The SI-ALS is a disease-specific self-report scale, which provides a robust interval-level measure of spasticity in ALS. Spasticity has a substantial impact on quality of life in ALS.

The Neurological Sleep Index: A suite of new sleep scales for multiple sclerosis.

OBJECTIVE: The objective of this study was to develop patient-reported outcome measures for sleep dysfunction and sleepiness in multiple sclerosis (MS), since there are currently no MS-specific measurement tools for these clinically important entities. METHODS: Items were generated from semi-structured interviews followed by cognitive debrief. A 42-item pool was administered to patients with MS at three neuroscience centres in the UK. Comparator scales were co-administered. Constructs were validated by Rasch analysis, guided by initial exploratory factor analysis. RESULTS: There were two supraordinate qualitative themes of diurnal sleepiness and non-restorative nocturnal sleep. Rasch analysis on 722 records produced three scales, which corresponded to diurnal sleepiness, non-restorative nocturnal sleep and fragmented nocturnal sleep. All had excellent fit parameters, were unidimensional and were free from differential item functioning. A summed raw score cut-point of 31/48 in the Diurnal Sleepiness Scale equated to the standard cut-point of 10 on the Epworth Sleepiness Scale (ESS). CONCLUSION: Three high-quality measurement scales were developed, and together they compose the Neurological Sleep Index for MS (NSI-MS). The Diurnal Sleepiness Scale might provide an alternative to the ESS. The Non-Restorative Nocturnal Sleep Scale and the Fragmented Nocturnal Sleep Scale appear to be the only such measures for use in MS.

Poststroke fatigue: the patient perspective.

PURPOSE: Fatigue is reported as a prevalent symptom post stroke. The purpose of this study is to explore the patent perspective of this symptom, how it is experienced, and its subjective impact on the patient. METHOD: The qualitative procedure of interpretative phenomenological analysis (IPA) was used to analyze the narratives of 10 subjects with previous stroke, who each undertook a single, semi-structured interview. RESULTS: Fatigue was a salient symptom for all the patients. Six main themes were identified. Tiredness/sleep was recognized in all the narratives, and themes of restriction, frustration, and determination/coping reflected varying degrees of physical, cognitive, and psychological dimensions to fatigue. Depression/motivation was also identified, reflecting low mood and helplessness. The remaining theme support indicated a social dimension, with patients recognizing the need for professional and familial support. Further subthemes were identified, and the thematic descriptions of the physical and psychosocial aspects indicated the complexity of fatigue and unique patient profiles. A holistic overview of each narrative furthered an understanding of the dynamic interrelationships between these aspects and their impact on the patient. There were prevalent patterns, but these were different for each patient. CONCLUSION: A better understanding of the varied dimensions or themes elaborated for poststroke fatigue, and their interrelationships, should help in mitigating its impact. The analysis cautions against giving any simplistic and unitary advice to patients about dealing with fatigue.

Is the Epworth sleepiness scale suitable for use in stroke?

BACKGROUND: The Epworth Sleepiness Scale (ESS-8) is frequently used in stroke but has never been validated for this condition. There is concern regarding the suitability of the driving item (item 8). A summed raw score of 10 or more (from a maximum of 24) signifies pathological sleepiness. OBJECTIVE: To determine the construct validity of the ESS-8 by Rasch analysis and in particular to determine whether omission of item 8 confounds the scale. METHOD: A pack containing the ESS-8 and questions regarding sleep and demographics was sent to 999 patients who had experienced a stroke within the past 4 years. Data were assessed for fit to the Rasch model. RESULTS: Analysis of 269 records revealed a unidimensional scale that was free from differential item functioning by age and sex with good overall fit to the Rasch model. Item 4 had disordered thresholds. Analysis of the ESS without item 8 (ESS-7) also revealed a valid scale. Equating person locations between the ESS-8 and ESS-7 showed no differences below a summed raw score of 18. CONCLUSION: The ESS-8 has good construct validity for use in stroke and is reliable at the cutpoint of 10. Summed raw scores below 18 will be unaffected if nondrivers either score as zero or simply omit item 8. The scale is therefore robust for detecting cases of pathological sleepiness in stroke but may not be suitable for measuring high levels of sleepiness in a sample containing both drivers and nondrivers. Instead, the ESS-7 could be used for this purpose.

Perceived changes and minimum clinically important difference of the Neurological Fatigue Index for multiple sclerosis (NFI-MS).

The determination of the minimum clinically important difference (MCID) is an important aspect of scale development. The Neurological Fatigue Index for multiple sclerosis (NFI-MS) was administered before and after expected change or stability in fatigue in 208 multiple sclerosis (MS) patients. The overall change scores of the NFI-MS accorded with perceived direction of change; importantly, no change was seen when none was perceived. Using the interval level NFI-MS scores, the largest MCID equated to 2.49 points on the Summary scale, 2.36 points on the Physical scale, 0.84 points on the Cognitive scale, 0.97 on the Diurnal Sleep scale and 1.95 on the Nocturnal Sleep scale. Our conclusion is that the NFI-MS responds as expected to changes in fatigue and has desirably small MCID scores.

The unidimensional self-efficacy scale for MS (USE-MS): developing a patient based and patient reported outcome.

BACKGROUND: Self-efficacy concerns the individual's belief that he or she is capable of performing a certain task and producing a desired effect, i.e. it reflects the person's perceptions of their capability for specific tasks, as distinct from their actual ability. Self-efficacy has been shown to influence motivation, psychological well-being, adherence with treatment regimes and quality of life in multiple sclerosis and other conditions. OBJECTIVE: To develop a unidimensional scale of MS self-efficacy with robust psychometric properties, suitable for patient self report. METHODS: A questionnaire pack covering three MS self-efficacy scales, the Dispositional Resilience Scale and demographic data was posted to MS patients from two MS databases. Data underwent Rasch analysis. RESULTS: Response rate was 309/600 (51.5%). None of the existing MS self-efficacy scales were unidimensional. A new 12-item scale, created by combining items from our two scales, was shown to fit the Rasch model, was unidimensional, and invariant for gender, education and disease duration. CONCLUSION: The Unidimensional Self-Efficacy scale for MS (USE-MS) provides a simple summated scale for an ordinal estimate of a persons' self efficacy. A transformation to interval scaling is available for use in the calculation of change scores and effect sizes.

Rasch analysis of the Modified Fatigue Impact Scale (MFIS) in multiple sclerosis.

BACKGROUND: The 21-item Modified Fatigue Impact Scale (MFIS) has been recommended as an outcome measure for use in multiple sclerosis and is commonly used to generate an overall score of fatigue. OBJECTIVE: To test if the MFIS total score is valid by application of the Rasch measurement model. METHOD: The MFIS was sent by post to patients with clinically definite multiple sclerosis in two centres in the UK. Data were fitted to the Rasch model. RESULTS: Analysis was based on 415 records (55% response). The 21-item scale did not fit the Rasch model mainly because of multidimensionality. The scale was found to contain a "physical" dimension and a "cognitive" dimension, consistent with the original subscale structure. Valid physical and cognitive subscales were derived after deletion of some items. CONCLUSION: The MFIS cannot be used to generate a single overall score of fatigue. The conceptual interaction between the two dimensions remains unclear, which poses problems when interpreting change scores in these individual scales. Studies in which a global MFIS score was used as either an outcome measure or selection tool may need to be re-evaluated.

Central trigeminal involvement in multiple sclerosis using high-resolution MRI at 3 T.

Trigeminal neuralgia and sensory disturbance is common in multiple sclerosis (MS). Recent literature suggests that signal abnormalities in the cisternal trigeminal nerve and pontine root entry zone are seen in approximately 3% of MS patients, using conventional diagnostic MRI. The objective of this study was to determine the prevalence of trigeminal lesions using high-resolution MRI at 3T. Forty-seven patients with clinically definite MS, chosen at random from the outpatient population of a neuroscience centre underwent MRI on a Siemens 3T Trio machine. Three 3D sequences of T2 TSE (turbo spin echo), T2 FLAIR (fluid attenuated inversion recovery) and T1 IR (inversion recovery) were acquired in the coronal plane. The sequences were of contiguous 1 mm slices with in-plane resolution of up to 0.5 mm by 0.5 mm. Images were read by both a neurologist and a neuroradiologist. Any clinical history of trigeminal symptoms was determined for all subjects. The results showed that 11 patients (23%) had high signal in the trigeminal root entry zone and either the trans-cisternal nerve or pontine nucleus; example images are given. MRI changes did not correspond to clinical symptoms (chi square probability 1.000). The study concludes that high-resolution MRI at 3T yielded a high prevalence of detectable trigeminal abnormality in the MS sample studied. MRI involvement did not correspond to trigeminal symptoms.

A medical definition of fatigue in multiple sclerosis.

BACKGROUND: The symptom of fatigue has been described in a variety of ways but absence of a single taxonomy may be hindering research into this prevalent symptom. OBJECTIVE: To define the symptom of fatigue, as experienced by patients with multiple sclerosis (MS), in terms of a common framework, typical of a medical history. DESIGN: Qualitative phase followed by cross-sectional questionnaire survey. METHOD: Forty patients, with clinically definite MS, underwent semi-structured interviews which were analysed within a common framework of: experience (with derived themes of motor, cognitive, somatic/energy, sleep, other features) cadence (i.e. short-term variability), chronicity, precipitating and aggravating factors, relieving factors, severity and associated features. The prevalence of each feature of fatigue, emergent from the interviews, was subsequently determined by questionnaire survey of a further 635 MS patients. RESULTS: Despite variance across patients, fatigue could be described within the derived themes and framework. Nearly all themes were endorsed by the majority of questionnaire respondents. In summary, fatigue could be defined as reversible motor and cognitive impairment, with reduced motivation and desire to rest. It could appear spontaneously or may be brought on by mental or physical activity, humidity, acute infection and food ingestion. It was relieved by daytime sleep or rest without sleep. It could occur at any time but was usually worse in the afternoon. CONCLUSION: A framework, not only derived from patient experience but also meaningful in a medical context, was shown to be capable of describing fatigue in a large cross-section of MS patients. The definition may facilitate inter-disease comparison of fatigue as well as physiological enquiry.

Treatment for ataxia in multiple sclerosis.

BACKGROUND: Disabling tremor or ataxia is common in multiple sclerosis (MS) and up to 80% of patients experience tremor or ataxia at some point during their disease. A variety of treatments are available, ranging from pharmacotherapy or stereotactic neurosurgery to neurorehabilitation. OBJECTIVES: To assess the efficacy and tolerability of both pharmacological and non-pharmacologic treatments of ataxia in patients with MS. SEARCH STRATEGY: The following electronic resources were searched: Cochrane MS Group trials register (June 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2006), National Health Service National Research Register (NRR) including the Medical Research Council Clinical Trials Directory (Issue 2, 2006), MEDLINE (January 1996 to June 2006), and EMBASE (Jan 1988 to June 2006). Manual searches of bibliographies of relevant articles, pertinent medical and neurology journals and abstract books of major neurology and MS conferences (2001-2006) were also performed. Direct communication with experts and drug companies was sought. SELECTION CRITERIA: Blinded, randomised trials which were either placebo-controlled or which compared two or more treatments were included. Trials testing pharmacological agents must have had both participant and assessor blinding. Trials testing surgical interventions or effects of physiotherapy, where participants could not have been blinded to the treatment, must have had independent assessors who were blinded to the treatment. Cross-over trials were included. DATA COLLECTION AND ANALYSIS: Three independent reviewers extracted data and the findings of the trials were summarised. A meta-analysis was not performed due to the inadequacy of outcome measures and methodological problems with the studies reviewed. MAIN RESULTS: Ten randomised controlled trials met the inclusion criteria. Six placebo-controlled studies (pharmacotherapy) and four comparative studies (one stereotactic neurosurgery and three neurorehabilitation) were reviewed. No standardised outcome measures were used across the studies. In general, pharmacotherapies were unrewarding and data on neurosurgery or rehabilitation is insufficient to lead to a change in practice. AUTHORS' CONCLUSIONS: The absolute and comparative efficacy and tolerability of pharmacotherapies to treat ataxia in MS are poorly documented and no recommendations can be made to guide prescribing. Although studies on neurosurgery and neurorehabilitation showed promising results, the absolute indications for treating with those methods cannot be developed. Standardised, well validated measures of ataxia and tremor need to be developed and employed in larger randomised controlled trials with careful blinding.

3D MRI in multiple sclerosis: a study of three sequences at 3 T.

The objective of this study was to assess the feasibility of using 3D acquisition at 3 T for imaging patients with multiple sclerosis (MS). Feasibility was assessed by three criteria based on acquisition time, specific absorption rate (SAR) and image quality. 47 patients with clinically definite MS underwent imaging in a Siemens 3T Trio MR scanner. Patient safety data were obtained following the scan sessions. The study had local ethics approval. The following three-dimensional (3D) sequences, all acquired coronally, were used: T2 fluid attenuated inversion recovery (FLAIR) (repetition time (TR) 6000 ms, echo time (TE) 353 ms, inversion time (TI) 2200 ms), 0.5x0.5x1 mm voxels, acquisition time 10 min 38 s; T2 turbo spin echo (TSE) (TR 3000 ms, TE 354 ms), 1x1x1 mm voxels, acquisition time 8 min 29 s; T1 inversion recovery (IR) (TR 2040 ms, TE 5.56 ms, TI 1100 ms), matrix 512x448 (0.5x0.5 mm pixels), 0.5x0.5x1 mm voxels, acquisition time 7 min 38 s. Total acquisition time was 26 min 45 s. Example images are presented. 3D scanning at 3 T provides highly detailed, high quality images with acquisition times tolerated by MS patients, even by those with severe disability. The volumetric data are suitable for a wide variety of post-processing techniques; the authors suggest that 3D studies at 3 T should be considered as the possible brain imaging protocol for either cross-sectional or longitudinal studies in MS and that the 3D T2 FLAIR sequence should be considered for the purposes of radiological diagnosis.

Increased pre-operative platelet counts are a possible predictor for reduced sensitivity to heparin.

We investigated a possible relationship between pre-operative platelet count and reduced sensitivity to heparin in 87 patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Sensitivity to heparin was determined by measuring the slope of the heparin dose response (HDR) before surgery. Pre-operative platelet counts were measured as part of routine analysis of the patients' coagulation status. Patients with an HDR slope of <80 s u. ml(-1), were considered to have a reduced sensitivity to heparin and activated clotting time data were collected from these patients before and after heparin administration before CPB. A significant correlation was determined between pre-operative platelet levels and HDR slope (P<0.001). Platelet counts were significantly greater in heparin-resistant patients compared with those who had the expected response to the anticoagulant (P<0.05). This could be caused by an increased capacity to produce platelet factor 4, which neutralizes heparin.

Harnessing peer networks as an instrument for AIDS prevention: results from a peer-driven intervention.

OBJECTIVE: Since 1985, community outreach efforts to combat acquired immunodeficiency syndrome (AIDS) among injecting drug users (IDUs) in the United States have overwhelmingly depended on a provider-client model that relies on staffs of professional outreach workers. We report on a comparison of this traditional outreach model with an innovative social network model, termed "a peer-driven intervention" (PDI). The latter provides IDUs with guidance and structured incentives that permit them to play a much more active role in the outreach process, thereby harnessing peer pressure on behalf of human immunodeficiency virus (HIV) prevention efforts. METHODS: We compare the performance of a traditional outreach intervention (TOI) and a PDI that were implemented in medium-sized towns in eastern and central Connecticut. Comparisons are based on the number and representativeness of IDUs recruited at each site, the effectiveness of HIV prevention education, compliance rates with AIDS risk reduction recommendations, and relative cost. The analyses are based on 522 initial interviews and 190 six-month follow-up interviews conducted during the first two years of each intervention's operation. RESULTS: Both interventions produced significant reductions in HIV risk behaviors, as measured using self-reports. The PDI outperformed the traditional intervention with respect to the number of IDUs recruited, the ethnic and geographic representativeness of the recruits, and the effectiveness of HIV prevention education. In addition, the costs of recruiting IDUs into the intervention and educating them about HIV in the community was only one-thirtieth as much in the PDI as in the traditional intervention. CONCLUSIONS: The findings suggest that given guidance and nominal incentives, IDUs can play a more extensive role in community outreach efforts than the traditional model allows. The findings also suggest that both interventions reduce HIV-associated risk behaviors, but the PDI reaches a larger and more diverse set of IDUs, and does so at much less expense.

Impact of zidovudine plus lamivudine or zalcitabine on health-related quality of life.

OBJECTIVE: To assess the impact of treatment with zidovudine plus lamivudine or zalcitabine on health-related quality of life (HRQOL) in patients with HIV. DESIGN: HRQOL assessments were conducted as part of a double-blind, randomized, 24-week (extended to 52 wk) efficacy and safety study. The Medical Outcomes Study HIV Health Survey (MOS-HIV), which assesses 10 physical and psychological domains of HRQOL, was self-administered by patients at baseline and at weeks 16, 32, 52, or at treatment discontinuation. SETTING: Twenty-one outpatient centers in the US, Canada, and Puerto Rico. PATIENTS: The study enrolled 254 HIV-positive patients (CD4+ 100-300 cells/mm3); 206 patients completed the MOS-HIV at baseline and at least once during treatment. Post hoc analyses stratified patients into two subgroups: AIDS (CD4+ < 200 cells/mm3) and non-AIDS (CD4+ > or = 200 cells/mm3). INTERVENTIONS: Patients received zidovudine 200 mg three times daily plus one of the following: lamivudine 150 mg twice daily, lamivudine 300 mg twice daily, or zalcitabine 0.75 mg three times daily. MAIN OUTCOME MEASURE: Change in MOS-HIV scores from baseline to last completed questionnaire. RESULTS: Following an average of 36 weeks of treatment, there were statistically significant differences across treatment groups in mean change scores on the physical functioning, role functioning, and vitality scales, with stable or increased (improved) scores in the zidovudine plus lamivudine 150 mg group and decreased scores in the zidovudine plus zalcitabine and zidovudine plus lamivudine 300 mg groups for most scales. Post hoc analyses found that in the non-AIDS subgroup, only the zidovudine plus lamivudine 150 mg group had increases in mean MOS-HIV scores (on 8 of 10 scales); in the AIDS subgroup, all but two MOS-HIV scores (in the zidovudine plus zalcitabine group) decreased in all three treatment groups. CONCLUSIONS: These results suggest that, of the three combination therapies studied, zidovudine plus lamivudine 150 mg was most likely to maintain or improve HRQOL in HIV-positive patients.