Predicting time to serologic diagnosis of AQP4+ NMOSD based on clinical factors and social determinants of health.

BACKGROUND: Early serologic diagnosis and initiation of targeted therapy are associated with better outcomes in aquaporin-4 IgG positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD). OBJECTIVE: To determine predictors of time to serologic diagnosis of AQP4+ NMOSD. METHODS: In CANOPTICS, a multi-centre, Canadian cohort study of NMOSD, we retrospectively evaluated time from the first clinical attack to first positive AQP4-IgG serology. We used a multivariable negative binomial regression model to evaluate possible predictors of time to diagnosis. RESULTS: We identified 129 participants with AQP4+ NMOSD from 7 centres. Diagnostic delay of >1 month was observed in 82 (63.6 %). Asian compared to European (White) ethnicity (IRR:0.40, 95 % CI:0.21-0.78), female sex (IRR:0.56, 95 % CI:0.32-0.99), later calendar year (IRR:0.84, 95 % CI:0.81-0.86), and hospitalization for the first attack (IRR:0.35, 95 % CI:0.20-0.62) were associated with shorter times to serologic diagnosis. We did not observe any overall effect of Afro-Caribbean ethnicity, but in exploratory analyses, Afro-Caribbean individuals with low income had longer times to diagnosis. CONCLUSION: More than 60 % of patients with NMOSD experienced delays to AQP4-IgG serologic diagnosis in this cohort. Given evidence of more adverse long-term outcomes in Afro-Caribbean individuals with NMOSD, intersectional effects of ethnicity and social determinants of health merit further study.

A Canadian case control study investigating demographic and environmental factors associated with MOGAD.

BACKGROUND: Little is known about demographic and environmental factors associated with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). OBJECTIVE: To investigate factors associated with MOGAD using a case-control design and validated questionnaire from the Environmental Risk Factors in Multiple Sclerosis Study (EnvIMS). METHODS: We enrolled patients with positive MOG antibody serology and diagnosis of MOGAD at six Canadian centres. MOGAD participants completed the EnvIMS questionnaire, and were compared to unaffected controls from the Canadian arm of EnvIMS. We calculated crude and adjusted odds ratios (OR) using logistic regression models and Firth's procedure for rare events. RESULTS: We enrolled 39 MOGAD participants with mean (SD) age 45.0 (14.4) years, 28 (71.8 %) women, 25 (64.1 %) White, 26 (66.7 %) residents of Ontario, and mean BMI 28.6 (7.1). They were compared to 956 controls. Using multivariable logistic regression, larger body size at age 10 years (OR: 3.57, 95 % CI:1.23 - 10.33) and non-White ethnicity (OR:3.81, 95 % CI:1.93-7.54) were associated with higher odds of MOGAD. Among Ontario residents, current BMI ≥30 was associated with higher odds of MOGAD (OR:2.79, 95 % CI:1.03-7.53). CONCLUSION: Our findings are hypothesis-generating due to the sample size, but suggest that obesity and ethnicity should be explored as potential risk factors for MOGAD in other settings.

A national case-control study investigating demographic and environmental factors associated with NMOSD.

BACKGROUND: Risk factors for aquaporin-4 (AQP4+) antibody neuromyelitis optica spectrum disorder (NMOSD) are not well-established. OBJECTIVE: To investigate demographic and environmental factors associated with NMOSD using a validated questionnaire and case-control design. METHODS: We enrolled patients with AQP4 + NMOSD through six Canadian Multiple Sclerosis Clinics. Participants completed the validated Environmental Risk Factors in Multiple Sclerosis Study (EnvIMS) questionnaire. Their responses were compared to those of 956 unaffected controls from the Canadian arm of EnvIMS. We calculated odds ratios (ORs) for the association between each variable and NMOSD using logistic regression and Firth's procedure for rare events. RESULTS: In 122 participants (87.7% female) with NMOSD, odds of NMOSD in East Asian and Black participants were ⩾8 times that observed in White participants. Birthplace outside Canada was associated with an increased risk of NMOSD (OR = 5.5, 95% confidence interval (CI) = 3.6-8.3) as were concomitant autoimmune diseases (OR = 2.7, 95% CI = 1.4-5.0). No association was observed with reproductive history or age at menarche. CONCLUSION: In this case-control study, risk of NMOSD in East Asian and Black versus White individuals was greater than that observed in many previous studies. Despite the preponderance of affected women, we did not observe any association with hormonal factors such as reproductive history or age at menarche.

Non-compliance with disease modifying therapies in patients with Multiple Sclerosis: A qualitative analysis.

BACKGROUND: Factors associated with adherence to disease modifying therapies (DMT) in patients with Multiple Sclerosis (MS) have been reported before, but little has been studied on compliance to a physician's initial treatment recommendations. The objective of this study was to assess the factors associated with compliance to physician recommended treatment in treatment-naïve patients with MS. METHODS: We studied a cohort of patients with MS followed at an academic MS center in Toronto, Canada between January 2015 and May 2018. We used log-binomial models to identify patient-level factors (age, sex, and smoking history), and MS-specific clinical details (delay in diagnosis, and age at diagnosis) associated with compliance. RESULTS: Of the 332 patients, 256 (77.1%) were recommended DMT and 80 (31.3%) did not follow the recommendation. The most common causes for refusal to initiate DMT were: personal preference to not embark on a medication (46.2%), wishing to use a conservative approach (22.5%) or use of complementary medical approaches (18.8%). Twenty-one () patients who initially were compliant to treatment recommendations subsequently stopped DMT against medical advice. The two most common reasons for this nonadherence included adverse effects (61.8%) and personal preference (19.0%). Every year delay in the diagnosis of MS was associated with a lower risk of compliance (risk ratio 0.97, 95% CI, 0.94-1.00). CONCLUSION: Non-compliance to DMT recommendation in patients with MS in a Canadian practice is sizable, due to patients' own perspectives of disease and their belief in alternative complementary medicine.

Evaluation of ethnicity as a predictor of diagnostic phenotype and prognosis in neuromyelitis optica spectrum disorder in Toronto, Canada.

BACKGROUND: Recent international studies suggest that ethnicity may predict relapse types and outcomes in NMOSD. Our aim was to evaluate ethnicity as a predictor of diagnostic phenotype and prognosis in a multi-ethnic NMOSD cohort from a single geographic region. METHODS: This was a multi-centre retrospective cohort study of NMOSD subjects in Toronto, Canada. Ethnicity was classified as Asian, black, Caucasian, and other. Regression models were used to assess the relationship between ethnicity and each of diagnostic phenotype (2006 vs. only 2015 diagnostic criteria), annualized relapse rate, and EDSS at last follow-up. RESULTS: Out of 81 patients with NMOSD, 87.7% were female, 70.4% positive for aquaporin-4 (AQP4) IgG, with mean age of onset 38.9 (17) years and median disease duration [IQR] of 9.8 [4.50, 16.59] years. Blacks compared to Asians were less likely to exhibit classic NMO as per 2006 diagnostic criteria (p = 0.006). Caucasians, compared to Asians, had lower EDSS scores at last follow-up (p = 0.008) despite a trend towards higher annualized relapse rates. Older age of onset was significantly associated with greater disability as measured by the EDSS (p = 0.003). CONCLUSIONS: In this multi-ethnic cohort from Toronto, Canada, blacks with NMOSD were less likely than Asians to demonstrate classic NMO by 2006 diagnostic criteria. Caucasians had better long-term disability outcomes compared to Asians as measured by the EDSS.

Sequencing of high-efficacy disease-modifying therapies in multiple sclerosis: perspectives and approaches.

Multiple sclerosis (MS) is characterized by chronic inflammation in conjunction with neurodegeneration within the central nervous system. Most individuals with MS begin with a relapsing remitting course that later transitions to secondary progressive MS. Currently available disease-modifying therapies (DMTs) for relapsing MS have been demonstrated to reduce disease activity, however most patients require a change in therapy over the course of their disease. Treatment goals include the prevention of relapses and disability accumulation and to achieve this objective requires careful planning. Sequencing of DMTs for individual patients should be designed in such a way to maximize disease control and minimize risk based on the mechanism of action, pharmacokinetic and pharmacodynamic properties of each therapy. This includes the DMT patients are being switched from to those they are being switched to. The reversibility of immune system effects should be a key consideration for DMT sequence selection. This feature varies across DMTs and should factor more prominently in decision making as newer treatments become available for the prevention of disability accumulation in patients with progressive MS. In this short review, we discuss the landscape of existing therapies with an eye to the future when planning for optimal DMT sequencing. While no cure exists for MS, efforts are being directed toward research in neuroregeneration with the hope for positive outcomes.

Sequencing of disease-modifying therapies for relapsing-remitting multiple sclerosis: a theoretical approach to optimizing treatment.

Multiple sclerosis (MS) is a chronic disease which usually begins in young adulthood and is a lifelong condition. Individuals with MS experience physical and cognitive disability resulting from inflammation and demyelination in the central nervous system. Over the past decade, several disease-modifying therapies (DMTs) have been approved for the management of relapsing-remitting MS (RRMS), which is the most prevalent phenotype. The chronic nature of the disease and the multiple treatment options make benefit-risk-based sequencing of therapy essential to ensure optimal care. The efficacy and short- and long-term risks of treatment differ for each DMT due to their different mechanism of action on the immune system. While transitioning between DMTs, in addition to immune system effects, factors such as age, disease duration and severity, disability status, monitoring requirements, preference for the route of administration, and family planning play an important role. Determining a treatment strategy is therefore challenging as it requires careful consideration of the differences in efficacy, safety and tolerability, while at the same time minimizing risks of immune modulation. In this review, we discuss a sequencing approach for treating RRMS, with importance given to the long-term risks and individual preference when devising a treatment plan. Evidence-based strategies to counter breakthrough disease are also addressed.

Normal appearing white matter permeability: a marker of inflammation and information processing speed deficit among relapsing remitting multiple sclerosis patients.

PURPOSE: Blood-brain barrier breakdown (BBBB) occurs in relapsing remitting multiple sclerosis (RRMS). Relative recirculation (rR), a BBBB surrogate, may show inflammation undetectable by gadolinium. We compared normal appearing white matter (NAWM) rR in patients with and without disability measured with Symbol Digit Modalities Test and the Expanded Disability Status Scale (EDSS). METHODS: Thirty-nine RRMS patients were prospectively recruited and classified as impaired or non-impaired based on the SDMT and EDSS threshold ≥3. Significant demographic, MRI structural and regional rR characteristics were advanced into multivariate analysis to assess the association with impairment of cognition and EDSS. Bonferroni corrected p < 0.025 was applied to demographic and rR group comparisons; p < 0.05 was used in the final multivariate logistic regression. RESULTS: rR was higher in NAWM (p = 0.012), NAGM (p = 0.004), and basal ganglia (p = 0.007) in cognitively impaired versus non-impaired patients. The difference between NAWM and T2HL rR was significant in cognitively non-impaired patients and approximated that of T2HL in impairment (0.084 vs. 0.075, p = 0.008; 0.118 vs. 0.101, p = 0.091, respectively). After adjusting for confounders, rR elevation for NAWM (OR 1.777; 95% CI 1.068-2.956; p = 0.026), NAGM (OR 2.138; 1.100-4.157; p = 0.025), and basal ganglia (OR 2.192; 1.120-4.289; p = 0.022) remained significantly predictive of cognitive impairment. NAWM area under the curve (AUC) for cognitive impairment was 0.783. No significant group differences or associations were seen for rR and EDSS impairment. No NAGM and cortical lesion rR difference was present within any of the impaired or non-impaired groups. CONCLUSION: rR elevation in NAWM, NAGM, and basal ganglia appears sensitive to cognitive impairment but not EDSS.

Trial of Minocycline in a Clinically Isolated Syndrome of Multiple Sclerosis.

BACKGROUND: On the basis of encouraging preliminary results, we conducted a randomized, controlled trial to determine whether minocycline reduces the risk of conversion from a first demyelinating event (also known as a clinically isolated syndrome) to multiple sclerosis. METHODS: During the period from January 2009 through July 2013, we randomly assigned participants who had had their first demyelinating symptoms within the previous 180 days to receive either 100 mg of minocycline, administered orally twice daily, or placebo. Administration of minocycline or placebo was continued until a diagnosis of multiple sclerosis was established or until 24 months after randomization, whichever came first. The primary outcome was conversion to multiple sclerosis (diagnosed on the basis of the 2005 McDonald criteria) within 6 months after randomization. Secondary outcomes included conversion to multiple sclerosis within 24 months after randomization and changes on magnetic resonance imaging (MRI) at 6 months and 24 months (change in lesion volume on T2-weighted MRI, cumulative number of new lesions enhanced on T1-weighted MRI ["enhancing lesions"], and cumulative combined number of unique lesions [new enhancing lesions on T1-weighted MRI plus new and newly enlarged lesions on T2-weighted MRI]). RESULTS: A total of 142 eligible participants underwent randomization at 12 Canadian multiple sclerosis clinics; 72 participants were assigned to the minocycline group and 70 to the placebo group. The mean age of the participants was 35.8 years, and 68.3% were women. The unadjusted risk of conversion to multiple sclerosis within 6 months after randomization was 61.0% in the placebo group and 33.4% in the minocycline group, a difference of 27.6 percentage points (95% confidence interval [CI], 11.4 to 43.9; P=0.001). After adjustment for the number of enhancing lesions at baseline, the difference in the risk of conversion to multiple sclerosis within 6 months after randomization was 18.5 percentage points (95% CI, 3.7 to 33.3; P=0.01); the unadjusted risk difference was not significant at the 24-month secondary outcome time point (P=0.06). All secondary MRI outcomes favored minocycline over placebo at 6 months but not at 24 months. Trial withdrawals and adverse events of rash, dizziness, and dental discoloration were more frequent among participants who received minocycline than among those who received placebo. CONCLUSIONS: The risk of conversion from a clinically isolated syndrome to multiple sclerosis was significantly lower with minocycline than with placebo over 6 months but not over 24 months. (Funded by the Multiple Sclerosis Society of Canada; ClinicalTrials.gov number, NCT00666887 .).

Validation of a smartphone-based EEG among people with epilepsy: A prospective study.

Our objective was to assess the ability of a smartphone-based electroencephalography (EEG) application, the Smartphone Brain Scanner-2 (SBS2), to detect epileptiform abnormalities compared to standard clinical EEG. The SBS2 system consists of an Android tablet wirelessly connected to a 14-electrode EasyCap headset (cost ~ 300 USD). SBS2 and standard EEG were performed in people with suspected epilepsy in Bhutan (2014-2015), and recordings were interpreted by neurologists. Among 205 participants (54% female, median age 24 years), epileptiform discharges were detected on 14% of SBS2 and 25% of standard EEGs. The SBS2 had 39.2% sensitivity (95% confidence interval (CI) 25.8%, 53.9%) and 94.8% specificity (95% CI 90.0%, 97.7%) for epileptiform discharges with positive and negative predictive values of 0.71 (95% CI 0.51, 0.87) and 0.82 (95% CI 0.76, 0.89) respectively. 31% of focal and 82% of generalized abnormalities were identified on SBS2 recordings. Cohen's kappa (κ) for the SBS2 EEG and standard EEG for the epileptiform versus non-epileptiform outcome was κ = 0.40 (95% CI 0.25, 0.55). No safety or tolerability concerns were reported. Despite limitations in sensitivity, the SBS2 may become a viable supportive test for the capture of epileptiform abnormalities, and extend EEG access to new, especially resource-limited, populations at a reduced cost.

The relationship between white matter fiber damage and gray matter perfusion in large-scale functionally defined networks in multiple sclerosis.

BACKGROUND: Recent studies utilizing perfusion as a surrogate of cortical integrity show promise for overall cognition, but the association between white matter (WM) damage and gray matter (GM) integrity in specific functional networks is not previously studied. OBJECTIVE: To investigate the relationship between WM fiber integrity and GM node perfusion within six functional networks of relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS) patients. METHODS: Magnetic resonance imaging (MRI) and neurocognitive testing were performed on 19 healthy controls (HC), 39 RRMS, and 45 SPMS patients. WM damage extent and severity were quantified with T2-hyper/T1-hypointense (T2h/T1h) lesion volume and degree of perfusion reduction in lesional and normal-appearing white matter (NAWM), respectively. A two-step linear regression corrected for confounders was employed. RESULTS: Cognitive impairment was present in 20/39 (51%) RRMS and 25/45 (53%) SPMS patients. GM node perfusion was associated with WM fiber damage severity (WM hypoperfusion) within each network-including both NAWM ( R2 = 0.67-0.89, p < 0.0001) and T2h ( R2 = 0.39-0.62, p < 0.0001) WM regions-but was not significantly associated ( p > 0.01) with WM fiber damage extent (i.e. T2h/T1h lesion volumes). CONCLUSION: Overall, GM node perfusion was associated with severity rather than extent of WM network damage, supporting a primary etiology of GM hypoperfusion.

Attitudes to cannabis and patterns of use among Canadians with multiple sclerosis.

BACKGROUND: Canada has the highest incidence of MS worldwide. Anecdotal evidence reveals that people with MS smoke, ingest or vaporize cannabis for a multiplicity of reasons. With the legal situation in relation to use currently in flux, we undertook a study investigating patterns of use amongst people with MS and their attitudes towards the drug. METHODS: A consecutive sample of people with MS (n=246) attending a neurology (n=118) and a neuropsychiatry (n=107) clinic was enrolled and asked to complete a questionnaire containing demographic, disease and cannabis related variables. RESULTS: Of the 246 people approached, 225 (91.8%) agreed to participant. Attitude towards cannabis revealed that 122 (54.3%) participants approved of the drug while 75 (33.2%) were neutral. Legalization was endorsed by 98 (43.7%) participants, while 98 (43.7%) were in favour of legalization for medical use only. Current use was endorsed by 44 (19.5%) people with 125 (56.1%) reporting lifetime use. If cannabis were legal, 113 (50.2%) participants would use it. The most common symptoms for which cannabis was being used were: sleep (86%), pain (75%), anxiety (73%) and spasticity (68%). Participants attending the neuropsychiatry clinic were more likely to use cannabis for managing depression (χ2=4.99; p=0.03) and pain (χ2=3.85; p=0.05). CONCLUSION: There is a wide acceptance of cannabis within the MS patient community. One in five people currently use the drug for reasons that differ between neuropsychiatry and neurology clinics. Use could potentially more than double if the drug were legalized.

The spectrum of neurological presentations in an outpatient clinic of rural Zimbabwe.

BACKGROUND: Previous studies to estimate burden of neurological disorders in Africa are limited to inpatients in urban hospitals. The spectrum of neurological conditions in rural Africa remains unclear. OBJECTIVE: To determine the spectrum of neurological presentations in an outpatient setting in rural Zimbabwe. METHODS: Clinical data was collected from outpatient records at Karanda Mission Hospital, a rural community hospital in Northern Zimbabwe from February 2013 to February 2014. Each patient visit was entered in an outpatient record book by a registered nurse or a nurse trainee. Demographic details such as age, sex, weight and address of the patient, and clinical details such as diagnosis on discharge and medications prescribed were recorded in the record book following assessment by a physician or nurse practitioner. Each visit corresponded to a separate entry in the study. RESULTS: We recorded a total of 19,206 visits in the outpatient registry. The average age was 46.41 years (standard deviation=21.46), and there were more visits from women (57.81%). 11.63% (2233) of all visits had a neurological diagnosis at discharge. The most common neurological diagnoses were epilepsy/seizures (24.38%), followed by neuropathies (13.63%), headaches (11.4%) and strokes (4.6%). CONCLUSIONS: One in ten cases in an outpatient setting in rural Zimbabwe were neurologically related. Further studies are required to determine the public health burden of neurological disorders in rural Africa. The development and funding of educational initiatives in resource-limited areas is needed to improve neurological diagnosis and care.

Perfusion reduction in the absence of structural differences in cognitively impaired versus unimpaired RRMS patients.

BACKGROUND: Cognitive impairment affects 40%-68% of relapsing-remitting multiple sclerosis (RRMS) patients. Gray matter (GM) demyelination is complicit in cognitive impairment, yet cortical lesions are challenging to image clinically. We wanted to determine whether cortical cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) differences exist between cognitively impaired (CI) and unimpaired (NI) RRMS. METHODS: Prospective study of healthy controls (n = 19), CI (n = 20), and NI (n = 19) undergoing magnetic resonance imaging (MRI) and cognitive testing <1 week apart. White matter (WM) T2 hyperintense lesions and T1 black holes were traced. General linear regression assessed the relationship between lobar WM volume and cortical and WM CBF, CBV, and MTT. Relationship between global and lobar cortical CBF, CBV, and MTT and cognitive impairment was tested using a generalized linear model. Adjusted Bonferroni p < 0.005 was considered significant. RESULTS: No significant differences for age, gender, disease duration, and any fractional brain or lesion volume were demonstrated for RRMS subgroups. Expanded Disability Status Scale (EDSS) and Hospital Anxiety and Depression Scale-Depression (HADS-D) were higher in CI. Lobar cortical CBF and CBV were associated with cognitive impairment (p < 0.0001) after controlling for confounders. Cortical CBV accounted for 7.2% of cognitive impairment increasing to 8.7% with cortical CBF (p = 0.06), while WM and cortical CBF accounted for 8.2% of variance (p = 0.04). CONCLUSION: Significant cortical CBF and CBV reduction was present in CI compared to NI in the absence of structural differences.

Regional reduction in cortical blood flow among cognitively impaired adults with relapsing-remitting multiple sclerosis patients.

PURPOSE: Detection of cortical abnormalities in relapsing-remitting multiple sclerosis (RRMS) remains elusive. Structural magnetic resonance imaging (MRI) measures of cortical integrity are limited, although functional techniques such as pseudo-continuous arterial spin labeling (pCASL) show promise as a surrogate marker of disease severity. We sought to determine the utility of pCASL to assess cortical cerebral blood flow (CBF) in RRMS patients with (RRMS-I) and without (RRMS-NI) cognitive impairment. METHODS: A total of 19 age-matched healthy controls and 39 RRMS patients were prospectively recruited. Cognition was assessed using the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) battery. Cortical CBF was compared between groups using a mass univariate voxel-based morphometric analysis accounting for demographic and structural variable covariates. RESULTS: Cognitive impairment was present in 51.3% of patients. Significant CBF reduction was present in the RRMS-I compared to other groups in left frontal and right superior frontal cortex. Compared to healthy controls, RRMS-I displayed reduced CBF in the frontal, limbic, parietal and temporal cortex, and putamen/thalamus. RRMS-I demonstrated reduced left superior frontal lobe cortical CBF compared to RRMS-NI. No significant cortical CBF differences were present between healthy controls and RRMS-NI. CONCLUSION: Significant cortical CBF reduction occurs in RRMS-I compared to healthy controls and RRMS-NI in anatomically significant regions after controlling for structural and demographic differences.

EDSS Change Relates to Physical HRQoL While Relapse Occurrence Relates to Overall HRQoL in Patients with Multiple Sclerosis Receiving Subcutaneous Interferon ß -1a.

Objective. To compare patterns of associations of changes in mental and physical health dimensions of health-related quality of life (HRQoL) over time with relapse occurrence and changes in Expanded Disability Status Scale (EDSS) scores in patients with relapsing multiple sclerosis (RMS). Methods. This 24-month, phase IV, observational study enrolled 334 patients with RMS who received interferon ß-1a 44 µg or 22 µg subcutaneously three times weekly. At each 6-month visit, patients completed the Multiple Sclerosis Quality of Life-54 (MSQOL-54) and site investigators assessed EDSS and recorded relapse occurrence. A generalized linear model procedure was used for multivariable analyses (per protocol) that explored unique associations of EDSS score change and relapse occurrence with MSQOL-54 physical health composite score (PCS) and mental health composite score (MCS). Results. HRQoL improved over 2 years among those who completed the study. Occurrence of ≥1 relapse was significantly associated with lower MSQOL-54 PCS and MCS. Changes in EDSS score were significantly associated with MSQOL-54 PCS, but not MCS. Conclusions. HRQoL assessments, particularly those that examine mental health, may provide information on the general health status of patients with RMS that would not be recognized using traditional clinician-assessed measures of disease severity and activity. This trial is registered with ClinicalTrials.gov; identifier: NCT01141751.

Two Multiple Sclerosis Quality-of-Life Measures: Comparison in a National Sample.

BACKGROUND: Multiple sclerosis (MS) has a profound impact on patients' health-related quality of life (HRQoL). It is unclear how HRQoL can be best assessed for different purposes. This study aimed to compare two HRQoL questionnaires of differing lengths for feasibility of administration, patient perceptions and psychometric properties. METHODS: This was an open-label, 24-month study in 334 patients with relapsing MS treated with subcutaneous interferon ß-1a. At baseline and months 6, 12, 18 and 24, patients completed the Multiple Sclerosis International Quality of Life (MusiQoL) and Multiple Sclerosis Quality of Life-54 (MSQOL-54) questionnaires and compared them using an evaluation questionnaire. HRQoL scores over time and psychometric properties (correlations with clinical disease measures, relative validity and responsiveness to change) of the questionnaires were assessed. RESULTS: A minority of patients had missing items on either HRQoL measure. Completion time was significantly shorter for MusiQoL versus MSQOL-54 (p<0.0001). Patients felt that MusiQoL was easier to use than MSQOL-54 but preferred MSQOL-54 in terms of thoroughness. Mean HRQoL scores increased significantly from baseline to 24 months; correlations of both measures were stronger with an anxiety and depression measure than with disability or recent relapse occurrence. Relative validity and responsiveness to change were similar for both instruments. CONCLUSION: The shorter MusiQoL is suitable for evaluating HRQoL in patients with MS and may be more practical to administer than the more thorough MSQOL-54.

Impact of a formal mentoring program on academic promotion of Department of Medicine faculty: a comparative study.

PURPOSE: To evaluate the impact of a formal mentoring program on time to academic promotion and differences in gender-based outcomes. METHODS: Comparisons of time to promotion (i) before and after implementation of a formal mentoring program and (ii) between mentored and non-mentored faculty matched for covariates. Using paired-samples t-testing and mixed repeated measures ANCOVA, we explored the effect of mentor assignment and influence of gender on time to promotion. RESULTS: Promotional data from 1988 to 2010 for 382 faculty members appointed before 2003 were compared with 229 faculty members appointed in 2003 or later. Faculty appointed in 2003 or later were promoted 1.2 years (mean) sooner versus those appointed before 2003 (3.7 [SD = 1.7] vs. 2.5 [SD = 2], p < 0.0001). Regardless of year of appointment, mentor assignment appears to be significantly associated with a reduction in time to promotion versus non-mentored (3.4 [SD = 2.4] vs. 4.4 [SD = 2.6], p = 0.011). Gender effects were statistically insignificant. Post hoc analyses of time to promotion suggested that observed differences are not attributable to temporal effects, but rather assignment to a mentor. CONCLUSIONS: Mentoring was a powerful predictor of promotion, regardless of the year of appointment and likely benefited both genders equally. University resource allocation in support of mentoring appears to accelerate faculty advancement.