St Joseph's Health Care

OBJECTIVE: The 1980 American College of Rheumatology (ACR) classification criteria for systemic sclerosis (SSc) lack sensitivity for early SSc and limited cutaneous SSc. The present work, by a joint committee of the ACR and the European League Against Rheumatism (EULAR), was undertaken for the purpose of developing new classification criteria for SSc. METHODS: Using consensus methods, 23 candidate items were arranged in a multicriteria additive point system with a threshold to classify cases as SSc. The classification system was reduced by clustering items and simplifying weights. The system was tested by 1) determining specificity and sensitivity in SSc cases and controls with scleroderma-like disorders, and 2) validating against the combined view of a group of experts on a set of cases with or without SSc. RESULTS: It was determined that skin thickening of the fingers extending proximal to the metacarpophalangeal joints is sufficient for the patient to be classified as having SSc; if that is not present, 7 additive items apply, with varying weights for each: skin thickening of the fingers, fingertip lesions, telangiectasia, abnormal nailfold capillaries, interstitial lung disease or pulmonary arterial hypertension, Raynaud's phenomenon, and SSc-related autoantibodies. Sensitivity and specificity in the validation sample were, respectively, 0.91 and 0.92 for the new classification criteria and 0.75 and 0.72 for the 1980 ACR classification criteria. All selected cases were classified in accordance with consensus-based expert opinion. All cases classified as SSc according to the 1980 ACR criteria were classified as SSc with the new criteria, and several additional cases were now considered to be SSc. CONCLUSION: The ACR/EULAR classification criteria for SSc performed better than the 1980 ACR criteria for SSc and should allow for more patients to be classified correctly as having the disease.

Multifactorial mechanisms underlying late-onset Alzheimer's disease (LOAD) are poorly characterized from an integrative perspective. Here spatiotemporal alterations in brain amyloid-β deposition, metabolism, vascular, functional activity at rest, structural properties, cognitive integrity and peripheral proteins levels are characterized in relation to LOAD progression. We analyse over 7,700 brain images and tens of plasma and cerebrospinal fluid biomarkers from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Through a multifactorial data-driven analysis, we obtain dynamic LOAD-abnormality indices for all biomarkers, and a tentative temporal ordering of disease progression. Imaging results suggest that intra-brain vascular dysregulation is an early pathological event during disease development. Cognitive decline is noticeable from initial LOAD stages, suggesting early memory deficit associated with the primary disease factors. High abnormality levels are also observed for specific proteins associated with the vascular system's integrity. Although still subjected to the sensitivity of the algorithms and biomarkers employed, our results might contribute to the development of preventive therapeutic interventions.

In Brief Purpose: Oncologic concerns from high wound recurrence rates prompted a multi-institutional randomized trial to test the hypothesis that disease-free and overall survival are equivalent, regardless of whether patients receive laparoscopic-assisted or open colectomy. Methods: Eight hundred seventy-two patients with curable colon cancer were randomly assigned to undergo laparoscopic-assisted or open colectomy at 1 of 48 institutions by 1 of 66 credentialed surgeons. Patients were followed for 8 years, with 5-year data on 90% of patients. The primary end point was time to recurrence, tested using a noninferiority trial design. Secondary endpoints included overall survival and disease-free survival. (Kaplan–Meier) Results: As of March 1, 2007, 170 patients have recurred and 252 have died. Patients have been followed a median of 7 years (range 5–10 years). Disease-free 5-year survival (Open 68.4%, Laparoscopic 69.2%, P = 0.94) and overall 5-year survival (Open 74.6%, Laparoscopic 76.4%, P = 0.93) are similar for the 2 groups. Overall recurrence rates were similar for the 2 groups (Open 21.8%, Laparoscopic 19.4%, P = 0.25). These recurrences were distributed similarly between the 2 treatment groups. Sites of first recurrence were distributed similarly between the treatment arms (Open: wound 0.5%, liver 5.8%, lung 4.6%, other 8.4%; Laparoscopic: wound 0.9%, liver 5.5%, lung 4.6%, other 6.1%). Conclusion: Laparoscopic colectomy for curable colon cancer is not inferior to open surgery based on long-term oncologic endpoints from a prospective randomized trial. A multicenter prospective trial of 872 patients randomly assigned to undergo laparoscopic or open colectomy for curable cancer was performed. Laparoscopic colectomy for curable colon cancer is not inferior to open surgery based on 5-year overall survival, disease-free survival, and overall and site-specific rates of recurrence.

OBJECTIVE: To determine whether land-based therapeutic exercise is beneficial for people with knee osteoarthritis (OA) in terms of reduced joint pain or improved physical function and quality of life. METHODS: Five electronic databases were searched, up until May 2013. Randomised clinical trials comparing some form of land-based therapeutic exercise with a non-exercise control were selected. Three teams of two review authors independently extracted data and assessed risk of bias for each study. Standardised mean differences immediately after treatment and 2-6 months after cessation of formal treatment were separately pooled using a random effects model. RESULTS: In total, 54 studies were identified. Overall, 19 (35%) studies reported adequate random sequence generation, allocation concealment and adequately accounted for incomplete outcome data. However, research results may be vulnerable to selection, attrition and detection bias. Pooled results from 44 trials indicated that exercise significantly reduced pain (12 points/100; 95% CI 10 to 15) and improved physical function (10 points/100; 95% CI 8 to 13) to a moderate degree immediately after treatment, while evidence from 13 studies revealed that exercise significantly improved quality of life immediately after treatment with small effect (4 points/100; 95% CI 2 to 5). In addition, 12 studies provided 2-month to 6-month post-treatment sustainability data which showed significantly reduced knee pain (6 points/100; 95% CI 3 to 9) and 10 studies which showed improved physical function (3 points/100; 95% CI 1 to 5). CONCLUSIONS: Among people with knee osteoarthritis, land-based therapeutic exercise provides short-term benefit that is sustained for at least 2-6 months after cessation of formal treatment.

BACKGROUND: Knee osteoarthritis (OA) is a major public health issue because it causes chronic pain, reduces physical function and diminishes quality of life. Ageing of the population and increased global prevalence of obesity are anticipated to dramatically increase the prevalence of knee OA and its associated impairments. No cure for knee OA is known, but exercise therapy is among the dominant non-pharmacological interventions recommended by international guidelines. OBJECTIVES: To determine whether land-based therapeutic exercise is beneficial for people with knee OA in terms of reduced joint pain or improved physical function and quality of life. SEARCH METHODS: Five electronic databases were searched, up until May 2013. SELECTION CRITERIA: All randomised controlled trials (RCTs) randomly assigning individuals and comparing groups treated with some form of land-based therapeutic exercise (as opposed to exercise conducted in the water) with a non-exercise group or a non-treatment control group. DATA COLLECTION AND ANALYSIS: Three teams of two review authors independently extracted data, assessed risk of bias for each study and assessed the quality of the body of evidence for each outcome using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach. We conducted analyses on continuous outcomes (pain, physical function and quality of life) immediately after treatment and on dichotomous outcomes (proportion of study withdrawals) at the end of the study; we also conducted analyses on the sustained effects of exercise on pain and function (two to six months, and longer than six months). MAIN RESULTS: In total, we extracted data from 54 studies. Overall, 19 (20%) studies reported adequate random sequence generation and allocation concealment and adequately accounted for incomplete outcome data; we considered these studies to have an overall low risk of bias. Studies were largely free from selection bias, but research results may be vulnerable to performance and detection bias, as only four of the RCTs reported blinding of participants to treatment allocation, and, although most RCTs reported blinded outcome assessment, pain, physical function and quality of life were participant self-reported.High-quality evidence from 44 trials (3537 participants) indicates that exercise reduced pain (standardised mean difference (SMD) -0.49, 95% confidence interval (CI) -0.39 to -0.59) immediately after treatment. Pain was estimated at 44 points on a 0 to 100-point scale (0 indicated no pain) in the control group; exercise reduced pain by an equivalent of 12 points (95% CI 10 to 15 points). Moderate-quality evidence from 44 trials (3913 participants) showed that exercise improved physical function (SMD -0.52, 95% CI -0.39 to -0.64) immediately after treatment. Physical function was estimated at 38 points on a 0 to 100-point scale (0 indicated no loss of physical function) in the control group; exercise improved physical function by an equivalent of 10 points (95% CI 8 to 13 points). High-quality evidence from 13 studies (1073 participants) revealed that exercise improved quality of life (SMD 0.28, 95% CI 0.15 to 0.40) immediately after treatment. Quality of life was estimated at 43 points on a 0 to 100-point scale (100 indicated best quality of life) in the control group; exercise improved quality of life by an equivalent of 4 points (95% CI 2 to 5 points).High-quality evidence from 45 studies (4607 participants) showed a comparable likelihood of withdrawal from exercise allocation (event rate 14%) compared with the control group (event rate 15%), and this difference was not significant: odds ratio (OR) 0.93 (95% CI 0.75 to 1.15). Eight studies reported adverse events, all of which were related to increased knee or low back pain attributed to the exercise intervention provided. No study reported a serious adverse event.In addition, 12 included studies provided two to six-month post-treatment sustainability data on 1468 participants for knee pain and on 1279 (10 studies) participants for physical function. These studies indicated sustainability of treatment effect for pain (SMD -0.24, 95% CI -0.35 to -0.14), with an equivalent reduction of 6 (3 to 9) points on 0 to 100-point scale, and of physical function (SMD -0.15 95% CI -0.26 to -0.04), with an equivalent improvement of 3 (1 to 5) points on 0 to 100-point scale.Marked variability was noted across included studies among participants recruited, symptom duration, exercise interventions assessed and important aspects of study methodology. Individually delivered programmes tended to result in greater reductions in pain and improvements in physical function, compared to class-based exercise programmes or home-based programmes; however between-study heterogeneity was marked within the individually provided treatment delivery subgroup. AUTHORS' CONCLUSIONS: High-quality evidence indicates that land-based therapeutic exercise provides short-term benefit that is sustained for at least two to six months after cessation of formal treatment in terms of reduced knee pain, and moderate-quality evidence shows improvement in physical function among people with knee OA. The magnitude of the treatment effect would be considered moderate (immediate) to small (two to six months) but comparable with estimates reported for non-steroidal anti-inflammatory drugs. Confidence intervals around demonstrated pooled results for pain reduction and improvement in physical function do not exclude a minimal clinically important treatment effect. Since the participants in most trials were aware of their treatment, this may have contributed to their improvement. Despite the lack of blinding we did not downgrade the quality of evidence for risk of performance or detection bias. This reflects our belief that further research in this area is unlikely to change the findings of our review.

BackgroundPregnant women with type 1 diabetes are a high-risk population who are recommended to strive for optimal glucose control, but neonatal outcomes attributed to maternal hyperglycaemia remain suboptimal. Our aim was to examine the effectiveness of continuous glucose monitoring (CGM) on maternal glucose control and obstetric and neonatal health outcomes.MethodsIn this multicentre, open-label, randomised controlled trial, we recruited women aged 18–40 years with type 1 diabetes for a minimum of 12 months who were receiving intensive insulin therapy. Participants were pregnant (≤13 weeks and 6 days' gestation) or planning pregnancy from 31 hospitals in Canada, England, Scotland, Spain, Italy, Ireland, and the USA. We ran two trials in parallel for pregnant participants and for participants planning pregnancy. In both trials, participants were randomly assigned to either CGM in addition to capillary glucose monitoring or capillary glucose monitoring alone. Randomisation was stratified by insulin delivery (pump or injections) and baseline glycated haemoglobin (HbA1c). The primary outcome was change in HbA1c from randomisation to 34 weeks' gestation in pregnant women and to 24 weeks or conception in women planning pregnancy, and was assessed in all randomised participants with baseline assessments. Secondary outcomes included obstetric and neonatal health outcomes, assessed with all available data without imputation. This trial is registered with ClinicalTrials.gov, number NCT01788527.FindingsBetween March 25, 2013, and March 22, 2016, we randomly assigned 325 women (215 pregnant, 110 planning pregnancy) to capillary glucose monitoring with CGM (108 pregnant and 53 planning pregnancy) or without (107 pregnant and 57 planning pregnancy). We found a small difference in HbA1c in pregnant women using CGM (mean difference −0·19%; 95% CI −0·34 to −0·03; p=0·0207). Pregnant CGM users spent more time in target (68% vs 61%; p=0·0034) and less time hyperglycaemic (27% vs 32%; p=0·0279) than did pregnant control participants, with comparable severe hypoglycaemia episodes (18 CGM and 21 control) and time spent hypoglycaemic (3% vs 4%; p=0·10). Neonatal health outcomes were significantly improved, with lower incidence of large for gestational age (odds ratio 0·51, 95% CI 0·28 to 0·90; p=0·0210), fewer neonatal intensive care admissions lasting more than 24 h (0·48; 0·26 to 0·86; p=0·0157), fewer incidences of neonatal hypoglycaemia (0·45; 0·22 to 0·89; p=0·0250), and 1-day shorter length of hospital stay (p=0·0091). We found no apparent benefit of CGM in women planning pregnancy. Adverse events occurred in 51 (48%) of CGM participants and 43 (40%) of control participants in the pregnancy trial, and in 12 (27%) of CGM participants and 21 (37%) of control participants in the planning pregnancy trial. Serious adverse events occurred in 13 (6%) participants in the pregnancy trial (eight [7%] CGM, five [5%] control) and in three (3%) participants in the planning pregnancy trial (two [4%] CGM and one [2%] control). The most common adverse events were skin reactions occurring in 49 (48%) of 103 CGM participants and eight (8%) of 104 control participants during pregnancy and in 23 (44%) of 52 CGM participants and five (9%) of 57 control participants in the planning pregnancy trial. The most common serious adverse events were gastrointestinal (nausea and vomiting in four participants during pregnancy and three participants planning pregnancy).InterpretationUse of CGM during pregnancy in patients with type 1 diabetes is associated with improved neonatal outcomes, which are likely to be attributed to reduced exposure to maternal hyperglycaemia. CGM should be offered to all pregnant women with type 1 diabetes using intensive insulin therapy. This study is the first to indicate potential for improvements in non-glycaemic health outcomes from CGM use.FundingJuvenile Diabetes Research Foundation, Canadian Clinical Trials Network, and National Institute for Health Research.

BACKGROUND AND PURPOSE: Hemiparesis resulting in functional limitation of an upper extremity is common among stroke survivors. Although existing evidence suggests that increasing intensity of stroke rehabilitation therapy results in better motor recovery, limited evidence is available on the efficacy of virtual reality for stroke rehabilitation. METHODS: In this pilot, randomized, single-blinded clinical trial with 2 parallel groups involving stroke patients within 2 months, we compared the feasibility, safety, and efficacy of virtual reality using the Nintendo Wii gaming system (VRWii) versus recreational therapy (playing cards, bingo, or "Jenga") among those receiving standard rehabilitation to evaluate arm motor improvement. The primary feasibility outcome was the total time receiving the intervention. The primary safety outcome was the proportion of patients experiencing intervention-related adverse events during the study period. Efficacy, a secondary outcome measure, was evaluated with the Wolf Motor Function Test, Box and Block Test, and Stroke Impact Scale at 4 weeks after intervention. RESULTS: Overall, 22 of 110 (20%) of screened patients were randomized. The mean age (range) was 61.3 (41 to 83) years. Two participants dropped out after a training session. The interventions were successfully delivered in 9 of 10 participants in the VRWii and 8 of 10 in the recreational therapy arm. The mean total session time was 388 minutes in the recreational therapy group compared with 364 minutes in the VRWii group (P=0.75). There were no serious adverse events in any group. Relative to the recreational therapy group, participants in the VRWii arm had a significant improvement in mean motor function of 7 seconds (Wolf Motor Function Test, 7.4 seconds; 95% CI, -14.5, -0.2) after adjustment for age, baseline functional status (Wolf Motor Function Test), and stroke severity. CONCLUSIONS: VRWii gaming technology represents a safe, feasible, and potentially effective alternative to facilitate rehabilitation therapy and promote motor recovery after stroke.

Support vector ordinal regression (SVOR) is a popular method to tackle ordinal regression problems. However, until now there were no effective algorithms proposed to address incremental SVOR learning due to the complicated formulations of SVOR. Recently, an interesting accurate on-line algorithm was proposed for training ν -support vector classification (ν-SVC), which can handle a quadratic formulation with a pair of equality constraints. In this paper, we first present a modified SVOR formulation based on a sum-of-margins strategy. The formulation has multiple constraints, and each constraint includes a mixture of an equality and an inequality. Then, we extend the accurate on-line ν-SVC algorithm to the modified formulation, and propose an effective incremental SVOR algorithm. The algorithm can handle a quadratic formulation with multiple constraints, where each constraint is constituted of an equality and an inequality. More importantly, it tackles the conflicts between the equality and inequality constraints. We also provide the finite convergence analysis for the algorithm. Numerical experiments on the several benchmark and real-world data sets show that the incremental algorithm can converge to the optimal solution in a finite number of steps, and is faster than the existing batch and incremental SVOR algorithms. Meanwhile, the modified formulation has better accuracy than the existing incremental SVOR algorithm, and is as accurate as the sum-of-margins based formulation of Shashua and Levin.

The efficacy of arthroscopic surgery for the treatment of osteoarthritis of the knee is unknown.

Abstract The heterogeneity of neurodegenerative diseases is a key confound to disease understanding and treatment development, as study cohorts typically include multiple phenotypes on distinct disease trajectories. Here we introduce a machine-learning technique—Subtype and Stage Inference (SuStaIn)—able to uncover data-driven disease phenotypes with distinct temporal progression patterns, from widely available cross-sectional patient studies. Results from imaging studies in two neurodegenerative diseases reveal subgroups and their distinct trajectories of regional neurodegeneration. In genetic frontotemporal dementia, SuStaIn identifies genotypes from imaging alone, validating its ability to identify subtypes; further the technique reveals within-genotype heterogeneity. In Alzheimer’s disease, SuStaIn uncovers three subtypes, uniquely characterising their temporal complexity. SuStaIn provides fine-grained patient stratification, which substantially enhances the ability to predict conversion between diagnostic categories over standard models that ignore subtype ( p = 7.18 × 10 −4 ) or temporal stage ( p = 3.96 × 10 −5 ). SuStaIn offers new promise for enabling disease subtype discovery and precision medicine.

Tau is a hallmark pathology of Alzheimer's disease, and animal models have suggested that tau spreads from cell to cell through neuronal connections, facilitated by β-amyloid (Aβ). We test this hypothesis in humans using an epidemic spreading model (ESM) to simulate tau spread, and compare these simulations to observed patterns measured using tau-PET in 312 individuals along Alzheimer's disease continuum. Up to 70% of the variance in the overall spatial pattern of tau can be explained by our model. Surprisingly, the ESM predicts the spatial patterns of tau irrespective of whether brain Aβ is present, but regions with greater Aβ burden show greater tau than predicted by connectivity patterns, suggesting a role of Aβ in accelerating tau spread. Altogether, our results provide evidence in humans that tau spreads through neuronal communication pathways even in normal aging, and that this process is accelerated by the presence of brain Aβ.

Delirium is a common postoperative complication in older adults associated with adverse events including functional decline, longer lengths of stay, and risk of institutionalization. The purpose of this article is to systematically review preoperative risk factors associated with delirium following noncardiac surgery. A medical literature search was conducted using several bibliographic databases (PubMed, CINAHL, Cochrane, PsychInfo), supplemented by a manual search of the references of retrieved articles. Studies were retained for review after meeting strict inclusion criteria that included only operative patients with incident postoperative delirium diagnosed prospectively using criteria derived from the Diagnostic and Statistical Manual of Mental Disorders Third or Fourth Edition. Quantitative analyses included significance testing, homogeneity testing, and effect-size pooling. Twenty-five articles were included for review. The incidence of delirium ranged from 5.1% to 52.2%, with greater rates after hip fracture and aortic surgeries. This review found two scales, a clinical prediction rule, and a delirium risk classification system that were validated in other operative settings. Individual risk factor analysis suggested that cognitive impairment, older age, functional impairment, sensory impairment, depression, preoperative psychotropic drug use, psychopathological symptoms, institutional residence, and greater comorbidity were associated with postoperative delirium. Of the risk factors examined, evidence was most robust for an association between delirium and cognitive impairment or psychotropic drug use, with moderate effect sizes for both. Missing data and measurement differences did not allow for inferences to be made about other risk factors. Effect-size pooling supports the concept that delirium is a heterogeneous disorder with multiple risk factors. More research is needed to better identify patients at risk for postoperative delirium and to develop preventive strategies.

BACKGROUND: Current international treatment guidelines recommending therapeutic exercise for people with symptomatic hip osteoarthritis (OA) report are based on limited evidence. OBJECTIVES: To determine whether land-based therapeutic exercise is beneficial for people with hip OA in terms of reduced joint pain and improved physical function and quality of life. SEARCH METHODS: We searched five databases from inception up to February 2013. SELECTION CRITERIA: All randomised controlled trials (RCTs) recruiting people with hip OA and comparing some form of land-based therapeutic exercise (as opposed to exercises conducted in water) with a non-exercise group. DATA COLLECTION AND ANALYSIS: Four review authors independently selected studies for inclusion. We resolved disagreements through consensus. Two review authors independently extracted data, assessed risk of bias and the quality of the body of evidence for each outcome using the GRADE approach. We conducted analyses on continuous outcomes (pain, physical function and quality of life) and dichotomous outcomes (proportion of study withdrawals). MAIN RESULTS: We considered that seven of the 10 included RCTs had a low risk of bias. However, the results may be vulnerable to performance and detection bias as none of the RCTs were able to blind participants to treatment allocation and, while most RCTs reported blinded outcome assessment, pain, physical function and quality of life were participant self reported. One of the 10 RCTs was only reported as a conference abstract and did not provide sufficient data for the evaluation of bias risk.High-quality evidence from nine trials (549 participants) indicated that exercise reduced pain (standardised mean difference (SMD) -0.38, 95% confidence interval (CI) -0.55 to -0.20) and improved physical function (SMD -0.38, 95% CI -0.54 to -0.05) immediately after treatment. Pain and physical function were estimated to be 29 points on a 0- to 100-point scale (0 was no pain or loss of physical function) in the control group; exercise reduced pain by an equivalent of 8 points (95% CI 4 to 11 points; number needed to treat for an additional beneficial outcome (NNTB) 6) and improved physical function by an equivalent of 7 points (95% CI 1 to 12 points; NNTB 6). Only three small studies (183 participants) evaluated quality of life, with overall low quality evidence, with no benefit of exercise demonstrated (SMD -0.07, 95% CI -0.23 to 0.36). Quality of life was estimated to be 50 points on a norm-based mean (standard deviation (SD)) score of 50 (10) in the general population in the control group; exercise improved quality of life by 0 points. Moderate-quality evidence from seven trials (715 participants) indicated an increased likelihood of withdrawal from the exercise allocation (event rate 6%) compared with the control group (event rate 3%), but this difference was not significant (risk difference 1%; 95% CI -1% to 4%). Of the five studies reporting adverse events, each study reported only one or two events and all were related to increased pain attributed to the exercise programme.The reduction in pain was sustained at least three to six months after ceasing monitored treatment (five RCTs, 391 participants): pain (SMD -0.38, 95% CI -0.58 to -0.18). Pain was estimated to be 29 points on a 0- to 100-point scale (0 was no pain) in the control group, the improvement in pain translated to a sustained reduction in pain intensity of 8 points (95% CI 4 to 12 points) compared with the control group (0 to 100 scale). The improvement in physical function was also sustained (five RCTs, 367 participants): physical function (SMD -0.37, 95% CI -0.57 to -0.16). Physical function was estimated to be 24 points on a 0- to 100-point scale (0 was no loss of physical function) in the control group, the improvement translated to a mean of 7 points (95% CI 4 to 13) compared with the control group.Only five of the 10 RCTs exclusively recruited people with symptomatic hip OA (419 participants). There was no significant difference in pain or physical function outcomes compared with five studies recruiting participants with hip or knee OA (130 participants). AUTHORS' CONCLUSIONS: Pooling the results of these 10 RCTs demonstrated that land-based therapeutic exercise programmes can reduce pain and improve physical function among people with symptomatic hip OA.

The Papanicolaou smear, a routine screening test for cancer of the uterine cervix, was reported in 1928, and its efficacy was proved by 1941. Since then, it has been used worldwide as a clinical tool for the early detection of cancer. Cancer of the cervix follows a predictable sequence. Precancerous changes, not visible to the naked eye, are detected readily in cells sampled by the Papanicolaou smear. The evolution from the precancerous stage to cancer is slow, and routine annual screening makes this a curable cancer and totally preventable disease. This is the story of an ambitious and brilliant man, George Papanicolaou, and his devoted wife, Andromache Mavroyenous, whose discovery of the screening test is now recognized as the most significant advance in the control of cancer in the 20th century.

Task-oriented therapy is important. It makes intuitive sense that the best way to relearn a given task is to train specifically for that task. In animals, functional reorganization is greater for tasks that are meaningful to the animal. Repetition alone, without usefulness or meaning in terms of function, is not enough to produce increased motor cortical representations. In humans, less intense but task-specific training regimens with the more affected limb can produce cortical reorganization and associated, meaningful functional improvements.

OBJECTIVE: This in vivo (1)H magnetic resonance spectroscopy study examined levels of glutamate, glutamine, and N-acetylaspartate in patients experiencing their first episode of schizophrenia. METHOD: Localized in vivo (1)H spectra were acquired at 4.0 T from the left anterior cingulate and thalamus of 21 never-treated patients with schizophrenia and 21 comparable healthy volunteers. RESULTS: The level of glutamine was significantly higher in the left anterior cingulate cortex and thalamus of the patients with schizophrenia than in the healthy subjects. No differences were found between groups in the levels of other metabolites in the anterior cingulate or thalamus. CONCLUSIONS: Higher than normal glutamine levels in the left anterior cingulate and thalamus provide in vivo evidence of greater than normal glutamatergic activity proposed by glutamatergic models of schizophrenia. In contrast to other studies in chronically ill patients, no differences were seen in the levels of N-acetylaspartate in either location, suggesting that the findings in patients with chronic schizophrenia may be related to the effect of medication or the progression of the illness.

Alzheimer's disease (AD) is a progressive neurodegenerative condition marked by a decline in cognitive functions with no validated disease modifying treatment. It is critical for timely treatment to detect AD in its earlier stage before clinical manifestation. Mild cognitive impairment (MCI) is an intermediate stage between cognitively normal older adults and AD. To predict conversion from MCI to probable AD, we applied a deep learning approach, multimodal recurrent neural network. We developed an integrative framework that combines not only cross-sectional neuroimaging biomarkers at baseline but also longitudinal cerebrospinal fluid (CSF) and cognitive performance biomarkers obtained from the Alzheimer's Disease Neuroimaging Initiative cohort (ADNI). The proposed framework integrated longitudinal multi-domain data. Our results showed that 1) our prediction model for MCI conversion to AD yielded up to 75% accuracy (area under the curve (AUC) = 0.83) when using only single modality of data separately; and 2) our prediction model achieved the best performance with 81% accuracy (AUC = 0.86) when incorporating longitudinal multi-domain data. A multi-modal deep learning approach has potential to identify persons at risk of developing AD who might benefit most from a clinical trial or as a stratification approach within clinical trials.

The Global Study of Sexual Attitudes and Behaviors (GSSAB) investigated various aspects of sex and relationships among 27,500 men and women aged 40-80 years. Here, we report help-seeking behaviours for sexual problems in this population. A questionnaire was administered using the accepted survey method in each country. Although almost half of all sexually active respondents had experienced at least one sexual problem, less than 19% of them (18.0% of men and 18.8% of women) had attempted to seek medical help for their problem(s). The most frequent action taken by men and women was to talk to their partner (39%). Only 9% of men and women had been asked about their sexual health by a doctor in a routine visit during the past 3 years. Although sexual problems are highly prevalent, few men and women seek medical help for these problems. Overall, men and women show similar help-seeking behaviours.

BACKGROUND AND PURPOSE: Dysphagia occurs in 55% of all acute stroke patients. Early identification of dysphagia from screening can lead to earlier treatments and thereby reduce complications. We designed and validated a new bedside dysphagia screening tool-the Toronto Bedside Swallowing Screening Test (TOR-BSST) for stroke survivors in acute and rehabilitative settings. METHODS: The TOR-BSST initially contained 5 items with proven high predictive ability for dysphagia. Trained screeners administer and score the TOR-BSST in less than 10 minutes. Trained nurses from 2 acute and 2 rehabilitation facilities administered the TOR-BSST to consecutively admitted stroke inpatients. A positive screen identified patients at risk for dysphagia. Blinded repeat screenings were conducted within 24 hours. Test-retest reliability was established with the first 50 administrations at an ICC=0.92 (CI, 0.85 to 0.96). Items were eliminated if they contributed <or=5% to the total score and were judged clinically impractical. 20% of all enrolled patients were randomly allocated to gold standard videofluoroscopic assessment of swallowing and findings rated independently by 4 blinded experts. Adequate validity was set at sensitivity >or=90% and negative predictive value >or=90%. RESULTS: 311 stroke inpatients were enrolled; 103 acute and 208 rehabilitation. Screening was positive in 59.2% acute and 38.5% rehabilitation patients. The pharyngeal sensation item did not meet inclusion criteria and was eliminated. The TOR-BSST demonstrated excellent validity with sensitivity at 91.3% (CI, 71.9 to 98.7), and negative predictive values at 93.3% in acute and 89.5% in rehabilitation settings. CONCLUSIONS: The TOR-BSST is a simple accurate tool to identify stroke patients with dysphagia regardless of severity and setting.

BACKGROUND: Dementia can now be accurately diagnosed through clinical evaluation, cognitive screening, basic laboratory evaluation and structural imaging. A large number of ancillary techniques are also available to aid in diagnosis, but their role in the armamentarium of family physicians remains controversial. In this article, we provide physicians with practical guidance on the diagnosis of dementia based on recommendations from the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia, held in March 2006. METHODS: We developed evidence-based guidelines using systematic literature searches, with specific criteria for study selection and quality assessment, and a clear and transparent decision-making process. We selected studies published from January 1996 to December 2005 that pertained to key diagnostic issues in dementia. We graded the strength of evidence using the criteria of the Canadian Task Force on Preventive Health Care. RESULTS: Of the 1591 articles we identified on all aspects of dementia diagnosis, 1095 met our inclusion criteria; 620 were deemed to be of good or fair quality. From a synthesis of the evidence in these studies, we made 32 recommendations related to the diagnosis of dementia. There are clinical criteria for diagnosing most forms of dementia. A standard diagnostic evaluation can be performed by family physicians over multiple visits. It involves a clinical history (from patient and caregiver), a physical examination and brief cognitive testing. A list of core laboratory tests is recommended. Structural imaging with computed tomography or magnetic resonance imaging is recommended in selected cases to rule out treatable causes of dementia or to rule in cerebrovascular disease. There is insufficient evidence to recommend routine functional imaging, measurement of biomarkers or neuropsychologic testing. INTERPRETATION: The diagnosis of dementia remains clinically integrative based on history, physical examination and brief cognitive testing. A number of core laboratory tests are also recommended. Structural neuroimaging is advised in selected cases. Other diagnostic approaches, including functional neuroimaging, neuropsychological testing and measurement of biomarkers, have shown promise but are not yet recommended for routine use by family physicians.