Reliability, construct and concurrent validity of a smartphone-based cognition test in multiple sclerosis.

BACKGROUND: Early detection and monitoring of cognitive dysfunction in multiple sclerosis (MS) may be enabled with smartphone-adapted tests that allow frequent measurements in the everyday environment. OBJECTIVES: The aim of this study was to determine the reliability, construct and concurrent validity of a smartphone-adapted Symbol Digit Modalities Test (sSDMT). METHODS: During a 28-day follow-up, 102 patients with MS and 24 healthy controls (HC) used the MS sherpa® app to perform the sSDMT every 3 days on their own smartphone. Patients performed the Brief International Cognitive Assessment for MS at baseline. Test-retest reliability (intraclass correlation coefficients, ICC), construct validity (group analyses between cognitively impaired (CI), cognitively preserved (CP) and HC for differences) and concurrent validity (correlation coefficients) were assessed. RESULTS: Patients with MS and HC completed an average of 23.2 (SD = 10.0) and 18.3 (SD = 10.2) sSDMT, respectively. sSDMT demonstrated high test-retest reliability (ICCs > 0.8) with a smallest detectable change of 7 points. sSDMT scores were different between CI patients, CP patients and HC (all ps < 0.05). sSDMT correlated modestly with the clinical SDMT (highest r = 0.690), verbal (highest r = 0.516) and visuospatial memory (highest r = 0.599). CONCLUSION: Self-administered smartphone-adapted SDMT scores were reliable and different between patients who were CI, CP and HC and demonstrated concurrent validity in assessing information processing speed.

Performance validity in outpatients with multiple sclerosis and cognitive complaints.

BACKGROUND: Suboptimal performance during neuropsychological assessment renders cognitive test results invalid. However, suboptimal performance has rarely been investigated in multiple sclerosis (MS). OBJECTIVES: To investigate potential underlying mechanisms of suboptimal performance in MS. METHODS: Performance validity testing, neuropsychological assessments, neuroimaging, and questionnaires were analyzed in 99 MS outpatients with cognitive complaints. Based on performance validity testing patients were classified as valid or invalid performers, and based on neuropsychological test results as cognitively impaired or preserved. Group comparisons and correlational analyses were performed on demographics, patient-reported, and disease-related outcomes. RESULTS: Twenty percent displayed invalid performance. Invalid and valid performers did not differ regarding demographic, patient-reported, and disease-related outcomes. Disease severity of invalid and valid performers with cognitive impairment was comparable, but worse than cognitively preserved valid performers. Lower performance validity scores related to lower cognitive functioning, lower education, being male, and higher disability levels (p < 0.05). CONCLUSION: Suboptimal performance frequently occurs in patients with MS and cognitive complaints. In both clinical practice and in cognitive research, suboptimal performance should be considered in the interpretation of cognitive outcomes. Identification of factors that differentiate between suboptimal and optimal performers with cognitive impairment needs further exploration.

COVID-19 LNMA: COVID-19 living network meta-analysis: Drugs, antibodies, and cellular therapies for treatment and prophylaxis against COVID-19

This website provides up-to-date information about the use of pharmaceuticals, antiviral antibodies, and blood products in treatment and prevention of COVID-19. The evidence presented is the joint effort of an international group of researchers. The core group is based at McMaster University, and collaborates closely with the Magic Evidence Ecosystem Foundation and The BMJ. We also work independently of, but in collaboration with, the World Health Organization. This work is partially funded by the Canadian Institutes of Health Research operating grants VR4-172738 and MM1-174897

The BMJ Infographics

The BMJ infographics are selected information from an article, highlighting the key messages. BMJ infographics are reviewed by the authors, our technical and section editors and with some the peer reviewers before publication, and we're confident that they are accurate representations of the article. At the time of going to press, we make every effort to ensure that the information held in them is up-to-date. However, because of their innovative nature, we add disclaimers to them, to remind our readers that the information contained should be treated with the same caution as written articles. The graphics are often a summary of a summary - they shouldn't be taken to be the whole of the information available on the subject. Rare conditions/complications/etc will sometimes be excluded. While our infographics are not validated decision aids that have been extensively tested on clinicians or patients, we want them to be useful to readers in summarising recommendations or evidence. If you have any comments about their usability, we'd be glad to hear

Real-world keystroke dynamics are a potentially valid biomarker for clinical disability in multiple sclerosis.

BACKGROUND: Clinical measures in multiple sclerosis (MS) face limitations that may be overcome by utilising smartphone keyboard interactions acquired continuously and remotely during regular typing. OBJECTIVE: The aim of this study was to determine the reliability and validity of keystroke dynamics to assess clinical aspects of MS. METHODS: In total, 102 MS patients and 24 controls were included in this observational study. Keyboard interactions were obtained with the Neurokeys keyboard app. Eight timing-related keystroke features were assessed for reliability with intraclass correlation coefficients (ICCs); construct validity by analysing group differences (in fatigue, gadolinium-enhancing lesions on magnetic resonance imaging (MRI), and patients vs controls); and concurrent validity by correlating with disability measures. RESULTS: Reliability was moderate in two (ICC = 0.601 and 0.742) and good to excellent in the remaining six features (ICC = 0.760-0.965). Patients had significantly higher keystroke latencies than controls. Latency between key presses correlated the highest with Expanded Disability Status Scale (r = 0.407) and latency between key releases with Nine-Hole Peg Test and Symbol Digit Modalities Test (ρ = 0.503 and r = -0.553, respectively), ps < 0.001. CONCLUSION: Keystroke dynamics were reliable, distinguished patients and controls, and were associated with clinical disability measures. Consequently, keystroke dynamics are a promising valid surrogate marker for clinical disability in MS.

Coronavirus disease 2019 (COVID-19): The right clinical information, right where it's needed

A potentially severe acute respiratory infection caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).[1] The clinical presentation is generally that of a respiratory infection with a symptom severity ranging from a mild common cold-like illness, to a severe viral pneumonia leading to acute respiratory distress syndrome that is potentially fatal. Characteristic symptoms include fever, cough, and dyspnea, although some patients may be asymptomatic. Complications of severe disease include, but are not limited to, multi-organ failure, septic shock, and blood clots.

Kappa free light chains is a valid tool in the diagnostics of MS: A large multicenter study.

OBJECTIVE: To validate kappa free light chain (KFLC) and lambda free light chain (LFLC) indices as a diagnostic biomarker in multiple sclerosis (MS). METHODS: We performed a multicenter study including 745 patients from 18 centers (219 controls and 526 clinically isolated syndrome (CIS)/MS patients) with a known oligoclonal IgG band (OCB) status. KFLC and LFLC were measured in paired cerebrospinal fluid (CSF) and serum samples. Gaussian mixture modeling was used to define a cut-off for KFLC and LFLC indexes. RESULTS: The cut-off for the KFLC index was 6.6 (95% confidence interval (CI) = 5.2-138.1). The cut-off for the LFLC index was 6.9 (95% CI = 4.5-22.2). For CIS/MS patients, sensitivity of the KFLC index (0.88; 95% CI = 0.85-0.90) was higher than OCB (0.82; 95%CI = 0.79-0.85; p < 0.001), but specificity (0.83; 95% CI = 0.78-0.88) was lower (OCB = 0.92; 95% CI = 0.89-0.96; p < 0.001). Both sensitivity and specificity for the LFLC index were lower than OCB. CONCLUSION: Compared with OCB, the KFLC index is more sensitive but less specific for diagnosing CIS/MS. Lacking an elevated KFLC index is more powerful for excluding MS compared with OCB but the latter is more important for ruling in a diagnosis of CIS/MS.

Tobacco Control (Journal)

Tobacco Control is an international peer review journal covering the nature and consequences of tobacco use worldwide; tobacco's effects on population health, the economy, the environment, and society; efforts to prevent and control the global tobacco epidemic through population level education and policy changes; the ethical dimensions of tobacco control policies; and the activities of the tobacco industry and its allies.

Disease course heterogeneity and OCT in multiple sclerosis.

BACKGROUND: The heterogeneity of the disease course in multiple sclerosis (MS) remains a challenge for patient management and clinical trials. OBJECTIVE: The objective of this paper is to investigate the relationship between disease course heterogeneity and retinal layer thicknesses in MS. METHODS: A total of 230 MS patients and 63 healthy control subjects were included. Spectral-domain OCT scanning of the peripapillary and macular regions was performed, followed by automated eight-layer segmentation. Generalised estimation equations were used for comparisons. Receiver operating characteristic (ROC) curves were calculated for distinguishing a benign from a typical disease course. RESULTS: Primary progressive patients showed relative preservation of inner retinal layers, compared to the relapsing onset MS types. Only in MS eyes without optic neuritis did patients with typical MS show more severe thinning of the inner retinal layers (RNFL to INL) compared to patients with a benign disease course, even after an average disease course of 20 years. CONCLUSION: The thicknesses, particularly of the innermost retinal layers (RNFL, GCC), were significantly related to the heterogeneous disease course in MS. The relative preservation of these layers in primary progressive and benign MS suggests rather limited susceptibility of the retina to neurodegeneration, which may be relevant for future neurodegenerative treatment trials employing OCT as a secondary outcome measure in primary progressive MS.

Student BMJ

Página da revista eletrônica "Student BMJ" destinada para estudantes e médicos recém formados. Traz informações sobre a revista, submissões, artigos, estudo de casos, sistema de busca. É necessário cadastro gratuito para acesso irrestrito do conteúdo.

Open access capture of patients with gastroesophageal reflux disease using an online patient-reported outcomes instrument.

BACKGROUND: Persons with gastroesophageal reflux disease (GERD) frequently search online for information about causes and treatment options. The GerdQ self-assessment questionnaire can be used for diagnosis of GERD and follow-up of symptoms. OBJECTIVES: To assess whether it is feasible (1) to study the prevalence and impact of GERD in persons visiting a GERD information website, and (2) to identify partial responsiveness to proton pump inhibitor (PPI) therapy using the GerdQ. METHODS: All visitors (aged 18-79 years) to a GERD information website between November 2008 and May 2011 were invited to complete the GerdQ online. The GerdQ questionnaire consists of 6 questions (score per question: 0-3). In respondents who did not use PPIs, we used the questionnaire to identify those with GERD (total score ≥8) and assess the influence of these symptoms on their daily life, divided into low (total score <3 on impact questions) and high impact (total score ≥3 on impact questions). In PPI users, we used the GerdQ to quantify partial responsiveness by any report of heartburn, regurgitation, sleep disturbance, or over-the-counter medication use for more than 1 day in the preceding week. We subsequently asked GerdQ respondents scoring ≥8 to complete the disease-specific Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire. RESULTS: A total of 131,286 visitors completed the GerdQ, of whom 80.23% (n = 105,329) did not use a PPI. Of these, we identified 67,379 respondents (63.97%) to have GERD (n = 32,935; 48.88% high impact). We invited 14,028 non-PPI users to complete the QOLRAD questionnaire, of whom 1231 (8.78%) completed the questionnaire. Mean total QOLRAD scores were 5.14 (SEM 0.04) for those with high-impact GERD and 5.77 (SEM 0.04) for those with low-impact GERD (P < .001). In PPI users, 22,826 of 25,957 respondents (87.94%) reported partial responsiveness. We invited 6238 PPI users to complete the QOLRAD questionnaire, of whom 599 (9.60%) completed the disease-specific quality-of-life questionnaire. Mean total QOLRAD scores were 4.62 (SEM 0.05) for partial responders and 5.88 (SEM 0.14) for adequate responders (P < .001). CONCLUSIONS: The GerdQ identified GERD in many website respondents and measured partial responsiveness in the majority of PPI users. Both non-PPI users with GERD and PPI users with partial responsiveness were associated with a decreased health-related quality of life. We have shown the feasibility of GERD patient identification online.

Serotonin receptor 3A polymorphism c.-42C > T is associated with severe dyspepsia.

BACKGROUND: The association between anxiety and depression related traits and dyspepsia may reflect a common genetic predisposition. Furthermore, genetic factors may contribute to the risk of having increased visceral sensitivity, which has been implicated in dyspeptic symptom generation. Serotonin (5-HT) modulates visceral sensitivity by its action on 5-HT3 receptors. Interestingly, a functional polymorphism in HTR3A, encoding the 5-HT3 receptor A subunit, has been reported to be associated with depression and anxiety related traits. A functional polymorphism in the serotonin transporter (5-HTT), which terminates serotonergic signalling, was also found associated with these psychiatric comorbidities and increased visceral sensitivity in irritable bowel syndrome, which coexistence is associated with higher dyspeptic symptom severity. We investigated the association between these functional polymorphisms and dyspeptic symptom severity. METHODS: Data from 592 unrelated, Caucasian, primary care patients with dyspepsia participating in a randomised clinical trial comparing step-up and step-down antacid drug treatment (The DIAMOND trial) were analysed. Patients were genotyped for HTR3A c.-42C > T SNP and the 44 bp insertion/deletion polymorphism in the 5-HTT promoter (5-HTTLPR). Intensity of 8 dyspeptic symptoms at baseline was assessed using a validated questionnaire (0 = none; 6 = very severe). Sum score ≥20 was defined severe dyspepsia. RESULTS: HTR3A c.-42T allele carriers were more prevalent in patients with severe dyspepsia (OR 1.50, 95% CI 1.06-2.20). This association appeared to be stronger in females (OR 2.05, 95% CI 1.25-3.39) and patients homozygous for the long (L) variant of the 5-HTTLPR genotype (OR 2.00, 95% CI 1.01-3.94). Females with 5-HTTLPR LL genotype showed the strongest association (OR = 3.50, 95% CI = 1.37-8.90). CONCLUSIONS: The HTR3A c.-42T allele is associated with severe dyspeptic symptoms. The stronger association among patients carrying the 5-HTTLPR L allele suggests an additive effect of the two polymorphisms. These results support the hypothesis that diminished 5-HT3 mediated antinociception predisposes to increased visceral sensitivity of the gastrointestinal tract. Moreover, the HTR3A c.-42C > T and 5-HTTLPR polymorphisms likely represent predisposing genetic variants in common to psychiatric morbidity and dyspepsia.

Health equity in Brazil

Article published on 29 November, 2010, at the British Medical Journal - BMJ that considers progress and continued challenges towards health equity in Brazil, including information about the gradients in health status and access to health services.

Evidence-Based Nursing

It presents access to the Evidence-Based Nursing, an international digest of the evidence for nursing practice. It brings the current issue, issues archive, topic collections and free articles.

The distribution of new enhancing lesion counts in multiple sclerosis: further explorations.

BACKGROUND: A statistical distribution describing the number of new enhancing lesions seen on MRI in patients with MS is of great importance for improving the statistical methodology of clinical trials using new enhancing lesions as outcome measure. We examined whether there are superior alternatives for the currently proposed negative binomial (NB) distribution. OBJECTIVE: To determine the optimal statistical distribution describing new enhancing lesion counts from a selection of six conceivable models, and to assess the effect on the distribution of a treatment effect, varying follow-up duration and selection for activity at baseline. METHODS: The statistical NB, Poisson-Inverse Gaussian (P-IG), Poisson- Lognormal (P-LN), Neyman type A (NtA), Pólya-Aeppli (PA) and Zero Inflated Poisson (ZIP) distribution were fitted on new enhancing lesion data derived from one treated and two untreated cohorts of RRMS and relapsing SPMS patients and on subgroups of varying follow-up duration and selection for baseline activity. Measure of comparison was Akaike's information criterion (AIC). RESULTS: Both the subgroup analyses as well as a treatment had a noticeable effect on the distributional characteristics of new enhancing lesion counts. The NB distribution generally provided the most optimal fit, closely followed by the P-IG distribution and the P-LN distribution. Fits of the PA and NtA distribution were suboptimal, while the ZIP distribution was the least adequate for modelling new enhancing lesion counts. CONCLUSION: The NB distribution is the optimal distribution for modelling new enhancing lesion counts, irrespective of the effect of treatment, follow-up duration or a baseline activity selection criterion.