Comparing ocrelizumab to interferon/glatiramer acetate in people with multiple sclerosis over age 60.

BACKGROUND: Ongoing controversy exists regarding optimal management of disease modifying therapy (DMT) in older people with multiple sclerosis (pwMS). There is concern that the lower relapse rate, combined with a higher risk of DMT-related infections and side effects, may alter the risk-benefit balance in older pwMS. Given the lack of pwMS above age 60 in randomised controlled trials, the comparative efficacy of high-efficacy DMTs such as ocrelizumab has not been shown in older pwMS. We aimed to evaluate the comparative effectiveness of ocrelizumab, a high-efficacy DMT, versus interferon/glatiramer acetate (IFN/GA) in pwMS over the age of 60. METHODS: Using data from MSBase registry, this multicentre cohort study included pwMS above 60 who switched to or started on ocrelizumab or IFN/GA. We analysed relapse and disability outcomes after balancing covariates using an inverse probability treatment weighting (IPTW) method. Propensity scores were obtained based on age, country, disease duration, sex, baseline Expanded Disability Status Scale, prior relapses (all-time, 12 months and 24 months) and prior DMT exposure (overall number and high-efficacy DMTs). After weighting, all covariates were balanced. Primary outcomes were time to first relapse and annualised relapse rate (ARR). Secondary outcomes were 6-month confirmed disability progression (CDP) and confirmed disability improvement (CDI). RESULTS: A total of 248 participants received ocrelizumab, while 427 received IFN/GA. The IPTW-weighted ARR for ocrelizumab was 0.01 and 0.08 for IFN/GA. The IPTW-weighted ARR ratio was 0.15 (95% CI 0.06 to 0.33, p<0.001) for ocrelizumab compared with IFN/GA. On IPTW-weighted Cox regression models, HR for time to first relapse was 0.13 (95% CI 0.05 to 0.26, p<0.001). The hazard of first relapse was significantly reduced in ocrelizumab users after 5 months compared with IFN/GA users. However, the two groups did not differ in CDP or CDI over 3.57 years. CONCLUSION: In older pwMS, ocrelizumab effectively reduced relapses compared with IFN/GA. Overall relapse activity was low. This study adds valuable real-world data for informed DMT decision making with older pwMS. Our study also confirms that there is a treatment benefit in older people with MS, given the existence of a clear differential treatment effect between ocrelizumab and IFN/GA in the over 60 age group.

The Patient-Determined Disease Steps scale is not interchangeable with the Expanded Disease Status Scale in mild to moderate multiple sclerosis.

BACKGROUND AND PURPOSE: The validity, reliability, and longitudinal performance of the Patient-Determined Disease Steps (PDDS) scale is unknown in people with multiple sclerosis (MS) with mild to moderate disability. We aimed to examine the psychometric properties and longitudinal performance of the PDDS. METHODS: We included relapsing-remitting MS patients with an Expanded Disability Status Scale (EDSS) score of less than 4. Validity and test-retest reliability was examined. Longitudinal data were analysed with mixed-effect modelling and Cohen's kappa for concordance in confirmed disability progression (CDP). RESULTS: We recruited a total of 1093 participants, of whom 904 had complete baseline data. The baseline correlation between PDDS and EDSS was weak (ρ = 0.45, p < 0.001). PDDS had stronger correlations with patient-reported outcomes (PROs). Conversely, EDSS had stronger correlations with age, disease duration, Kurtzke's functional systems and processing speed test. PDDS test-retest reliability was good to excellent (concordance correlation coefficient = 0.73-0.89). Longitudinally, PDDS was associated with EDSS, age and depression. A higher EDSS score was associated with greater PDSS progression. The magnitude of these associations was small. There was no concordance in CDP as assessed by PDDS and EDSS. CONCLUSION: The PDDS has greater correlation with other PROs but less correlation with other MS-related outcome measures compared to the EDSS. There was little correlation between PDDS and EDSS longitudinally. Our findings suggest that the PDDS scale is not interchangeable with the EDSS.

Pituitary abscess: a case report and systematic review of 488 cases.

BACKGROUND: Pituitary abscess (PA) is a rare condition and not well understood. We aimed to describe a case and perform a comprehensive systematic review to explore presenting symptoms, radiological findings, endocrine abnormalities and mortality. AIM: To identify presenting symptoms, radiological findings, endocrinological abnormalities and predictors of mortality for PA. METHODS: We systematically reviewed the literature to identify all case reports of PA. Data regarding presentation, mortality, radiological findings, endocrinological abnormalities and treatment was extracted. RESULTS: We identified 488 patients from 218 articles meeting the inclusion criteria. Mortality was 5.1%, with days to presentation (OR 1.0005, 95% CI 1.0001-1.0008, p < 0.01) being the only identified independent predictor of mortality. Mortality rates have decreased over time, with cases published prior to 2000 having higher mortality rates (OR 6.92, 95% CI 2.80-17.90, p < 0.001). The most common symptom was headache (76.2%), followed by visual field defects (47.3%). Classical signs of infection were only present in 43%. The most common imaging feature on magnetic resonance imaging (MRI) was high T2 and low T1 signal of the pituitary gland with peripheral contrast enhancement. Over half (54.8%) were culture negative, with the most common bacterial organism being staphylococcus aureus (7.8%) and fungal organism being aspergillus (8.8%). The most common endocrine abnormality was hypopituitarism (41.1%), followed by diabetes insipidus (24.8%). Whilst symptoms resolved in most patients, persistent endocrine abnormalities were present in over half of patients (61.0%). CONCLUSION: PA is associated with significant mortality, with delayed presentation increasing risk of mortality. Ongoing endocrinological abnormalities are common. Given the non-specific clinical presentation, the appearance of high T2, low T1 and peripheral contrast enhancement of the pituitary on MRI should prompt consideration of this rare disease.

Smartphone monitoring of cognition in people with multiple sclerosis: A systematic review.

BACKGROUND: Current cognitive monitoring of people with multiple sclerosis (pwMS) is sporadic, resource intensive and insensitive for detection of real-world cognitive performance and decline. Smartphone applications may provide us with a more sensitive biomarker for cognitive decline that reflects real-world performance. The goal of this study was to perform a systematic review and qualitative synthesis of all current smartphone apps monitoring cognition in pwMS. METHODS: A systematic search of five major online databases (PubMed/Medline, Scopus, Web of Science, Cumulative Index of Nursing and Allied Health Literature and IEEE Xplore) was performed in accordance with the Cochrane Handbook and Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. We included all studies with at least one measure of phone-based digital biomarkers for monitoring cognition in pwMS above the age of 18. Two authors independently screened the articles retrieved. Data on test-retest reliability, validity coefficients, feasibility and practice effects were extracted from the studies identified. Critical appraisal of the studies was performed using the National Institute of Health quality assessment tool for observational cohort and cross-sectional studies. RESULTS: 12 articles covering six smartphone apps were included in this review. All articles had a low risk of bias, though sample size calculation was rarely performed. Of the six apps, five used smartphone versions of the symbol digit modalities test. The final app examined keystroke features passively. Test-retest reliability ranged from good to excellent. Concurrent validity was demonstrated through moderate to strong correlation with neuropsychological tests and weak to moderate correlations with EDSS, radiological biomarkers and patient-reported outcomes. Mobile apps performed comparably, and in some cases outperformed established cognitive tests. Whilst reported acceptability was high, significant attrition rates were present in longitudinal cohorts. There were significant short and long-term practice effects. Overall, smartphone versions of the SDMT showed strong psychometric properties across multiple apps. CONCLUSION: Smartphone applications are reliable and valid biomarkers of real-world cognition in pwMS. Further longitudinal data would allow for a better understanding of their predictive and ecological validity.

Clinical relevance of MRI knee abnormalities in Australian rules football players: a longitudinal study.

BACKGROUND/AIM: The clinical relevance of MRI knee abnormalities in athletes is unclear. This study aimed to determine the prevalence of MRI knee abnormalities in Australian Rules Football (ARF) players and describe their associations with pain, function, past and incident injury and surgery history. METHODS: 75 male players (mean age 21, range 16-30) from the Tasmanian State Football League were examined early in the playing season (baseline). History of knee injury/surgery and knee pain and function were assessed. Players underwent MRI scans of both knees at baseline. Clinical measurements and MRI scans were repeated at the end of the season, and incident knee injuries during the season were recorded. RESULTS: MRI knee abnormalities were common at baseline (67% bone marrow lesions, 16% meniscal tear/extrusion, 43% cartilage defects, 67% effusion synovitis). Meniscal tears/extrusion and synovial fluid volume were positively associated with knee symptoms, but these associations were small in magnitude and did not persist after further accounting for injury history. Players with a history of injury were at a greater risk of having meniscal tears/extrusion, effusion synovitis and greater synovial fluid volume. In contrast, players with a history of surgery were at a greater risk of having cartilage defects and meniscal tears/extrusion. Incident injuries were significantly associated with worsening symptoms, BML development and incident meniscal damage. CONCLUSIONS: MRI abnormalities are common in ARF players, are linked to a previous knee injury and surgery history, as well as incident injury but do not dictate clinical symptomatology.

Los teléfonos móviles como potencial vehículo de infección en un entorno hospitalario.

ResumenEl objetivo de este artículo es investigar el posible papel desempeñado por los teléfonos móviles como depósitos de colonización bacteriana y los factores de riesgo que ésta conlleva en un ambiente hospitalario. Entre enero de 2013 y marzo de 2014 examinamos a 226 miembros del personal de un hospital regional de Australia (146 médicos y 80 estudiantes de medicina). Los principales resultados de interés se relacionaron con los tipos de microorganismos y la cantidad de contaminación encontrados en los teléfonos móviles. Este estudio mostró la existencia de un alto nivel de contaminación bacteriana (n = 168/226, 74%) en los teléfonos móviles de los funcionarios de un hospital de atención terciaria, aislándose organismos similares en la mano dominante del personal y en sus teléfonos móviles. Mientras que la mayoría de los organismos aislados pertenecía a la flora cutánea normal, un pequeño porcentaje era potencialmente patógeno (n = 12/226, 5%). Además, se encontró que ser miembro subalterno del personal médico constituía un factor de riesgo para un importante crecimiento microbiano (OR 4.00, 95% CI 1.54, 10.37). Sólo 31% (70/226) de los participantes en el estudio informó que limpiaba sus teléfonos regularmente y sólo 21% (47/226) reportó que usa toallitas con alcohol para la limpieza de su teléfono. Este estudio demuestra que los teléfonos móviles son potenciales vehículos de bacterias patógenas en un ambiente hospitalario. Sólo una minoría de participantes informó que limpia su teléfono regularmente. Deberían elaborarse y aplicarse directrices de desinfección utilizando toallitas con alcohol.

Sinonasal teratocarcinosarcoma: a case report.

BACKGROUND: Sinonasal teratocarcinosarcoma is a rare and aggressive malignancy with histological features of both carcinosarcoma and teratoma. The optimal management of this malignancy is unclear, with most patients being managed by a combination of surgery and radiotherapy. CASE PRESENTATION: We describe an 83-year-old white woman with sinonasal teratocarcinosarcoma of her left nasal cavity treated with surgical debulking initially with radiological evidence of residual disease which was treated with radiotherapy (60 Gy in 30 fractions). A follow-up examination at 2 years showed no evidence of recurrence. CONCLUSIONS: In cases of sinonasal teratocarcinosarcoma with residual disease post-surgery, radiotherapy alone can be an effective option.

Venous thromboembolism in medical patients during hospitalisation and 3†months after hospitalisation: a prospective observational study.

OBJECTIVES: This study was conducted to assess the incidence and risk factors for venous thromboembolism (VTE) in a cohort of medical patients both during the period of hospitalisation and following discharge. DESIGN: This was a prospective observational study to document the risk profile and incidence of VTE posthospitalisation among all medical patients admitted to our institution during the trial period. SETTINGS: Primary healthcare. Single tertiary referral centre, Tasmania, Australia. PARTICIPANTS: A total of 986 patients admitted to the medical ward between January 2012 and September 2012 were included in the study with male to female ratio of 497:489. The mean age of patients was 68 years (range 17-112, SD 16). RESULTS: Overall, 54/986 patients (5.5%) had a VTE during the study period. Of these, 40/54 (74.1%) occurred during hospitalisation and 14/54 (25.9%) occurred following discharge. VTE risk factors revealed in multivariate analysis to be associated with a previous diagnosis of VTE (p<0.001, OR=6.63, 95% CI 3.3 to 13.36), the occurrence of surgery within the past 30 days (p<0.001, OR=2.52, 95% CI 1.33 to 4.79) and an admission diagnosis of pulmonary disease (p<0.01, OR 3.61, 95% CI 1.49 to 8.76). Mobility within 24 hours of admission was not associated with an increased risk. There was risk of VTE when the length of stay prolonged (p=0.046, OR=1.01, 95% CI 1.00 to 1.03), however it was not sustained with multivariate modelling. VTE-specific prophylaxis was used in 53% of the studied patients. Anticoagulation including antiplatelet agents were administered in 63% of patients who developed VTE. CONCLUSIONS: This prospective observational study found that 5.5% of the studied patients developed VTE. Among those, 25.9% (14/54) of patients had a detected VTE posthospitalisation with this risk being increased if there was a history of VTE, recent surgery and pulmonary conditions. Thromboprophylaxis may be worth considering in these cohorts. Further study to confirm these findings are warranted. TRIAL REGISTRATION NUMBER: ACTRN12611001255976.

Accelerometer-determined physical activity, muscle mass, and leg strength in community-dwelling older adults.

INTRODUCTION: The aim of this study was to describe the relationship between accelerometer-determined physical activity (PA), muscle mass, and lower-limb strength in community-dwelling older adults. METHODS: Six hundred thirty-six community-dwelling older adults (66 ± 7 years) were studied. Muscle mass was measured using dual-energy x-ray absorptiometry, whilst lower limb strength was measured via dynamometry. We measured minutes/day spent in sedentary, light, moderate, and vigorous intensity activity using Actigraph GT1M accelerometers. RESULTS: Participants spent a median of 583(Interquartile ratio (IQR) 522-646), 225(176-271), 27(12-45) and 0(0-0) min in sedentary, light, moderate, and vigorous activity, respectively. PA intensity was positively associated with both lean mass percentage and lower limb strength in a dose-response fashion. Sedentary activity was negatively associated with lean mass percentage, but not lower-limb strength. There was a positive association between PA and appendicular lean mass in men only. There was an interaction between age and activity; as age increased, the magnitude of the association of PA with lean mass percentage decreased. Those who adhered to the Australian Department of Health PA guidelines (moderate/vigorous PA >/=150 min/week) had greater lean mass percentage, appendicular lean mass, and lower limb strength. CONCLUSIONS: Using accelerometer technology, both the amount and intensity of accelerometer-determined PA had an independent, dose-response relationship with lean mass percentage and lower limb strength, with the largest effect for vigorous activity. Time spent in sedentary activity was negatively associated with lean mass percentage, but was not associated with lower limb strength. The magnitude of the association between PA and lean mass percentage decreased with age, suggesting that PA programmes may need to be modified with increasing age.

The clinical significance, natural history and predictors of bone marrow lesion change over eight years.

INTRODUCTION: There is increasing evidence to suggest that bone marrow lesions (BMLs) play a key role in the pathogenesis of osteoarthritis (OA). However, there is a lack of long term data. The aim of this study was to describe the natural history of knee BMLs, their association with knee pain and examine predictors of BML change over eight years. METHODS: A total of 198 subjects (109 adult offspring of subjects who had a knee replacement and 89 community-based controls) were studied. Knee pain and BML size were assessed at two and ten year visits. RESULTS: At the two year visit, 64% of participants (n = 127) had 229 BMLs (34% patella, 26% femoral and 40% tibial). Over eight years, 24% (55/229) increased in size, 55% (125/229) remained stable and 21% (49/229) decreased in size or resolved completely. Of the participants without BMLs at baseline, 52% (37/71) developed incident BMLs. CONCLUSION: In this midlife cohort, the proportion of BMLs increasing in size was similar to those decreasing in size with the majority remaining stable. Change in BMLs was predicted by BMI and strenuous activity. An increase in BML size or a new BML resulted in an increase in pain especially in males and those with a family history of OA.

The association between physical activity and reduced body fat lessens with age - results from a cross-sectional study in community-dwelling older adults.

INTRODUCTION: The aim of this study was to describe the relationship between accelerometer-determined physical activity (PA) and adiposity in community-dwelling older adults. In addition, we were interested in comparing the extent of correlation between questionnaire and accelerometer determined PA. METHODS: 636 community-dwelling older adults (66±7years) were studied. Adiposity was measured using dual-energy X-ray absorptiometry and BMI was calculated. We measured minutes/day spent in sedentary, light, moderate and vigorous intensity activity using both questionnaires and Actigraph GT1M accelerometers. RESULTS: Participants spent a median of 583(IQR 522-646), 225(176-271), 27(12-45) and 0(0-0) minutes in sedentary, light, moderate and vigorous activities respectively. There was a non linear dose-response inverse relationship between activity intensity and adiposity. After adjusting for age, sex and other levels of PA, for every 10minute increase in activity, total body fat decreased by 169g(95% CI 61-277), 905g(632-1178), and 2208g(759-3657) for light, moderate and vigorous activities respectively. There was an interaction between age and activity; as age increased, the magnitude of the effects of light and moderate activities on adiposity decreased. Sedentary minutes were not associated with adiposity after adjusting for time spent at other PA intensities. Questionnaire measures of PA were weakly correlated with body fat measures when compared to accelerometer determined PA. CONCLUSION: Both the amount and intensity of PA, but not sedentary time, have an independent dose-response association with adiposity. The association is much stronger using objective assessment compared to questionnaire. The magnitude of these associations decrease with age suggesting that physical activity programmes may need to be modified with increasing age.

Swimming training for asthma in children and adolescents aged 18 years and under.

BACKGROUND: Asthma is the most common chronic medical condition in children and a common reason for hospitalisation. Observational studies have suggested that swimming, in particular, is an ideal form of physical activity to improve fitness and decrease the burden of disease in asthma. OBJECTIVES: To determine the effectiveness and safety of swimming training as an intervention for asthma in children and adolescents aged 18 years and under. SEARCH METHODS: We searched the Cochrane Airways Group's Specialised Register of trials (CENTRAL), MEDLINE , EMBASE, CINAHL, in November 2011, and repeated the search of CENTRAL in July 2012. We also handsearched ongoing Clinical Trials Registers. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) and quasi-RCTs of children and adolescents comparing swimming training with usual care, a non-physical activity, or physical activity other than swimming. DATA COLLECTION AND ANALYSIS: We used standard methods specified in the Cochrane Handbook for Systematic reviews of Interventions. Two review authors used a standard template to independently assess trials for inclusion and extract data on study characteristics, risk of bias elements and outcomes. We contacted trial authors to request data if not published fully. When required, we calculated correlation coefficients from studies with full outcome data to impute standard deviation of changes from baseline. MAIN RESULTS: Eight studies involving 262 participants were included in the review. Participants had stable asthma, with severity ranging from mild to severe. All studies were randomised trials, three studies had high withdrawal rates. Participants were between five to 18 years of age, and in seven studies swimming training varied from 30 to 90 minutes, two to three times a week, over six to 12 weeks. The programme in one study gave 30 minutes training six times per week. The comparison was usual care in seven studies and golf in one study. Chlorination status of swimming pool was unknown for four studies. Two studies used non-chlorinated pools, one study used an indoor chlorinated pool and one study used a chlorinated but well-ventilated pool.No statistically significant effects were seen in studies comparing swimming training with usual care or another physical activity for the primary outcomes; quality of life, asthma control, asthma exacerbations or use of corticosteroids for asthma. Swimming training had a clinically meaningful effect on exercise capacity compared with usual care, measured as maximal oxygen consumption during a maximum effort exercise test (VO2 max) (two studies, n = 32), with a mean increase of 9.67 mL/kg/min; 95% confidence interval (CI) 5.84 to 13.51. A difference of equivalent magnitude was found when other measures of exercise capacity were also pooled (four studies, n = 74), giving a standardised mean difference (SMD) 1.34; 95% CI 0.82 to 1.86. Swimming training was associated with small increases in resting lung function parameters of varying statistical significance; mean difference (MD) for FEV1 % predicted 8.07; 95% CI 3.59 to 12.54. In sensitivity analyses, by risk of attrition bias or use of imputed standard deviations, there were no important changes on effect sizes. Unknown chlorination status of pools limited subgroup analyses.Based on limited data, there were no adverse effects on asthma control or occurrence of exacerbations. AUTHORS' CONCLUSIONS: This review indicates that swimming training is well-tolerated in children and adolescents with stable asthma, and increases lung function (moderate strength evidence) and cardio-pulmonary fitness (high strength evidence). There was no evidence that swimming training caused adverse effects on asthma control in young people 18 years and under with stable asthma of any severity. However whether swimming is better than other forms of physical activity cannot be determined from this review. Further adequately powered trials with longer follow-up periods are needed to better assess the long-term benefits of swimming.