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BACKGROUND: Venous thromboembolism (VTE), encompassing both deep vein thrombosis (DVT) and pulmonary embolism (PE), is a leading cause of morbidity and mortality worldwide. METHODS: GARFIELD-VTE is a prospective, non-interventional observational study of real-world treatment practices. We aimed to capture the 36-month clinical outcomes of 10,679 patients with objectively confirmed VTE enrolled between May 2014 and January 2017 from 415 sites in 28 countries. FINDINGS: A total of 6582 (61.6 %) patients had DVT alone, 4097 (38.4 %) had PE ± DVT. At baseline, 98.1 % of patients received anticoagulation (AC) with or without other modalities of therapy. The proportion of patients on AC therapy decreased over time: 87.6 % at 3 months, 73.0 % at 6 months, 54.2 % at 12 months and 42.0 % at 36 months. At 12-months follow-up, the incidences (95 % confidence interval [CI]) of all-cause mortality, recurrent VTE and major bleeding were 6.5 (7.0-8.1), 5.4 (4.9-5.9) and 2.7 (2.4-3.0) per 100 person-years, respectively. At 36-months, these decreased to 4.4 (4.2-4.7), 3.5 (3.2-2.7) and 1.4 (1.3-1.6) per 100 person-years, respectively. Over 36-months, the rate of all-cause mortality and major bleeds were highest in patients treated with parenteral therapy (PAR) versus oral anti-coagulants (OAC) and no OAC, and the rate of recurrent VTE was highest in patients on no OAC versus those on PAR and OAC. The most frequent cause of death after 36-month follow-up was cancer (n = 565, 48.6 %), followed by cardiac (n = 94, 8.1 %), and VTE (n = 38, 3.2 %). Most recurrent VTE events were DVT alone (n = 564, 63.3 %), with the remainder PE, (n = 236, 27.3 %), or PE in combination with DVT (n = 63, 7.3 %). INTERPRETATION: GARFIELD-VTE provides a global perspective of anticoagulation patterns and highlights the accumulation of events within the first 12 months after diagnosis. These findings may help identify treatment gaps for subsequent interventions to improve patient outcomes in this patient population. ispartof: THROMBOSIS RESEARCH vol:222 pages:31-39 ispartof: location:United States status: published

The monoclonal antibody ublituximab enhances antibody-dependent cellular cytolysis and produces B-cell depletion. Ublituximab is being evaluated for the treatment of relapsing multiple sclerosis.In two identical, phase 3, double-blind, double-dummy trials (ULTIMATE I and II), participants with relapsing multiple sclerosis were randomly assigned in a 1:1 ratio to receive intravenous ublituximab (150 mg on day 1, followed by 450 mg on day 15 and at weeks 24, 48, and 72) and oral placebo or oral teriflunomide (14 mg once daily) and intravenous placebo. The primary end point was the annualized relapse rate. Secondary end points included the number of gadolinium-enhancing lesions on magnetic resonance imaging (MRI) by 96 weeks and worsening of disability.A total of 549 participants were enrolled in the ULTIMATE I trial, and 545 were enrolled in the ULTIMATE II trial; the median follow-up was 95 weeks. In the ULTIMATE I trial, the annualized relapse rate was 0.08 with ublituximab and 0.19 with teriflunomide (rate ratio, 0.41; 95% confidence interval [CI], 0.27 to 0.62; P0.001); in the ULTIMATE II trial, the annualized relapse rate was 0.09 and 0.18, respectively (rate ratio, 0.51; 95% CI, 0.33 to 0.78; P = 0.002). The mean number of gadolinium-enhancing lesions was 0.02 in the ublituximab group and 0.49 in the teriflunomide group (rate ratio, 0.03; 95% CI, 0.02 to 0.06; P0.001) in the ULTIMATE I trial and 0.01 and 0.25, respectively (rate ratio, 0.04; 95% CI, 0.02 to 0.06; P0.001), in the ULTIMATE II trial. In the pooled analysis of the two trials, 5.2% of the participants in the ublituximab group and 5.9% in the teriflunomide group had worsening of disability at 12 weeks (hazard ratio, 0.84; 95% CI, 0.50 to 1.41; P = 0.51). Infusion-related reactions occurred in 47.7% of the participants in the ublituximab group. Serious infections occurred in 5.0% in the ublituximab group and in 2.9% in the teriflunomide group.Among participants with relapsing multiple sclerosis, ublituximab resulted in lower annualized relapse rates and fewer brain lesions on MRI than teriflunomide over a period of 96 weeks but did not result in a significantly lower risk of worsening of disability. Ublituximab was associated with infusion-related reactions. (Funded by TG Therapeutics; ULTIMATE I and II ClinicalTrials.gov numbers, NCT03277261 and NCT03277248.).

BACKGROUND Prognostication of myeloproliferative neoplasm (MPN) has always been challenging, even with the advent of Janus kinase 2 (JAK2 V617F) molecular studies. The survival pattern of patients diagnosed with MPN in developing countries is still undetermined. MATERIALS AND METHODS The national MPN registry conducted from 2009 to 2015 in Malaysia provided a comprehensive insight into the demographics, clinical characteristics and laboratory parameters of patients diagnosed with MPN nationwide. The study analysed the survival patterns and mortality outcomes and risk among 671 patients diagnosed with essential thrombocythaemia (ET), polycythaemia vera (PV), primary myelofibrosis (PMF) and unclassified MPN (MPN-U). Mortality status was traced and confirmed until the end of December 2018, with right censoring applied to patients alive beyond that. RESULTS The analysed cohort consisted of 283 (42.2%) ET, 269 (40.1%) PV, 62 (9.2%) PMF and 57 (8.5%) MPN-U incident cases with diagnosis made between 2007 and 2015. The majority of patients were male (52.3%) and Malay (48.9%), except for ET, in which the majority of patients were female (60.1%) and of Chinese origin (47.0%). Female patients were found to have significantly better overall survival (OS) rates in ET (p = 0.0285) and MPN-U (p = 0.0070). Patients with JAK2 V617F mutation were found to have marginally inferior OS over time. Multivariable Cox regression identified patients with increased age [hazard ratio (HR) 1.055, 95% CI 1.031; 1.064], reduced haemoglobin (HB) level (HR 0.886, 95% CI 0.831; 0.945, p = 0.0002), being male (HR 1.545, 95% CI 1.077; 2.217, p = 0.0182), and having MPN-U (HR 2.383, 95% CI 1.261; 4.503, p = 0.0075) and PMF (HR 1.975, 95% CI 1.054; 3.701, p = 0.0335) at increased risk for worse mortality outcomes. CONCLUSION Myeloproliferative neoplasm reduces patient survival. The degree of impact on survival varies according to sub-type, sex, bone marrow fibrosis and HB levels. The JAK2 V617F mutation was not found to affect the survival pattern or mortality outcome significantly.

Aim: Patients with relapsing–remitting multiple sclerosis (RRMS) treated with natalizumab have anecdotally reported a ‘feel-good experience’ (FGE). The authors characterized the FGE using survey data from patients with RRMS treated with natalizumab or other disease-modifying therapies (other-DMT). Methods: Questionnaire data from RRMS patients who use MyMSTeam, an online patient social network, were analyzed. Results: The survey included 347 patients (95 natalizumab; 252 other-DMT). More natalizumab than other-DMT patients self-reported having an FGE (62.1 vs 44.8%; p = 0.001) as well as other physical, emotional and cognitive benefits. Conclusion: This study demonstrates that physical, emotional and cognitive benefits were more commonly reported by patients treated with natalizumab than those treated with other disease-modifying therapies and helps characterize patient-reported factors associated with the FGE.

IntroductionA major site of secondhand smoke exposure for children and adults is the home. Few studies have evaluated the impact of e-cigarette or hookah use on home air quality, despite evidence finding toxic chemicals in secondhand e-cigarette aerosols and hookah smoke. We assessed the effect of e-cigarette and hookah use on home air quality and compared it with air quality in homes where cigarettes were smoked and where no smoking or e-cigarette use occurred.MethodsNon-smoking homes and homes where e-cigarettes, hookah or cigarettes were used were recruited in the New York City area (n=57) from 2015 to 2019. Particulate matter with diameter less than 2.5 µm (PM2.5), black carbon and carbon monoxide (CO) were measured during a smoking or vaping session, both in a ‘primary’ smoking room and in an adjacent ‘secondary’ room where no smoking or vaping occurred. Log transformed data were compared with postanalysis of variance Tukey simultaneous tests.ResultsUse of hookah significantly increased PM2.5levels compared with non-smoking homes, in both the primary and secondary rooms, while use of e-cigarettes increased PM2.5levels only in primary rooms. Additionally, in-home use of hookah resulted in greater CO concentrations than the use of cigarettes in primary rooms.ConclusionsUse of e-cigarettes or hookah increases air pollution in homes. For hookah, increases in PM2.5penetrated even into rooms adjacent to where smoking occurs. Extending smoke-free rules inside homes to include e-cigarette and hookah products is needed to protect household members and visitors from passive exposure to harmful aerosols and gases.

Introduction STRIVE was a 4-year, multicenter, observational, open-label, single-arm study of natalizumab treatment in anti-JC virus antibody-negative (JCV-negative) relapsing-remitting multiple sclerosis (RRMS) patients with disease duration ≤ 3 years. The objective of STRIVE was to examine no evidence of disease activity (NEDA) status and predictors of NEDA in natalizumab-treated patients with early RRMS. Methods Proportions of patients with NEDA were evaluated along with baseline predictors of NEDA, annualized relapse rate, 24-week confirmed disability worsening (CDW), magnetic resonance imaging assessments (T2 and gadolinium-enhancing lesions), and serious adverse events. Results In years 1 and 2, 56.1% (95% confidence interval [CI] 48.7–63.4%) and 73.6% (95% CI 66.2–80.2%) of patients (intent-to-treat population [N = 222]), respectively, achieved NEDA. In years 3 and 4, 84.6% (95% CI 78.0–89.9%) and 91.9% (95% CI 86.4–95.8%) of patients, respectively, achieved Clinical NEDA (no relapses or 24-week CDW). Baseline predictors of NEDA in year 4 were Expanded Disability Status Scale score ≤ 2.0 (odds ratio [OR] = 3.85 [95% CI 1.54–9.63]; p = 0.004) and T2 lesion volume > 4 cc (OR = 0.39 [95% CI 0.15–0.98]; p = 0.046), with the latter also predicting Clinical NEDA in year 4 (OR = 0.21 [95% CI 0.05–0.92]; p = 0.038). The cumulative probability of CDW at year 4 was 19.3%. Serious adverse events were reported in 11.3% of patients. Conclusion These results support the long-term safety and effectiveness of natalizumab. Baseline predictors of NEDA help to inform benefit-risk assessments of natalizumab treatment in JCV-negative patients with early RRMS. Trial Registration ClinicalTrials.gov identifier NCT01485003. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01722-w.

Aims Nocturia has been increasingly recognized as a potential manifestation of cardiovascular disease. However, the relationship between nocturia and electrocardiographic (ECG) abnormalities has not been studied. This study aims to characterize the diagnostic utility of nocturia in identifying left ventricular hypertrophy (LVH), left atrial enlargement (LAE), and prolonged QTc on ECG. Methods Retrospective analysis of nocturnal voiding frequency and contemporaneous ECG data from consecutive patients evaluated at a university-based outpatient cardiology clinic. Three sets of three incremental binary multiple logistic regression models controlling for (1) age, (2) sex and race, and (3) body mass index, hypertension, diabetes mellitus, and diuretic utilization were performed to determine whether nocturia was predictive of LVH, LAE, and prolonged QTc. Results Included patients (n = 143, 77.6% nocturia) were predominantly African-American (89.5%), female (74.1%), and obese (61.5%), of whom 44.1%, 41.3%, and 27.3% had LVH, LAE, and prolonged QTc, respectively. Older age, African-American race, obesity, hypertension, diuretic use, LVH, and LAE were significantly associated with nocturia on univariate analysis. No significant differences were observed in the strength of associations between nocturia and LVH, LAE, or QTc prolongation based on age. Nocturia independently predicted LVH in Models I-III (odds ratios [ORs], 2.99-3.20; relative risks [RRs], 1.18 for all, p ≤ .046) and LAE in Models I-III (ORs, 4.24-4.72; RRs, 1.21 for all, p ≤ .015). No significant associations were observed between nocturia and prolonged QTc. Conclusions Nocturia may be a risk marker for underlying structural cardiac abnormalities.

BACKGROUND: Groin pain is a common long-term complication of total hip arthroplasty (THA). Femoral head size has been proposed as one of the primary causes. The implants used in dual mobility (DM) THA have large outer-bearing articulations, which could increase the risk of post-operative groin pain. Hip resurfacing (HR), too, has been shown to be associated with a risk of groin pain. QUESTIONS/PURPOSES: The goals of this study were to compare the incidence of groin pain at 1 year after hip arthroplasty in patients with different femoral head diameters and in patients undergoing conventional THA, DM THA, and HR. METHODS: After combing an institutional registry for all patients who had undergone THA or HR for primary hip osteoarthritis, we included 3193 patients in the analysis; 2008 underwent conventional THA, 416 underwent DM THA, and 769 underwent HR. We used logistic regression modeling to analyze the relation of groin pain at 1 year after surgery to patient demographics and clinical characteristics, including age, sex, body mass index (BMI), University of California at Los Angeles activity score at 1 year after surgery, bearing couple, and the ratio of acetabular diameter to femoral head diameter. We also measured cup inclination and anteversion in a subset of patients with and without groin pain at 1 year to assess whether pain could be related to implant position. RESULTS: Overall, 8.7% of patients reported groin pain at 1 year. Patients with groin pain were younger and had lower BMIs. There were increased odds of groin pain with a greater cup-to-head ratio, although DM implants, interestingly, were not significantly associated with groin pain; this may be attributable to so much of their movement taking place inside the implant. Subgroup analysis measuring cup inclination and anteversion showed no difference in cup position between patients with and without pain. CONCLUSION: In this population of hip arthroplasty patients, the incidence of groin pain 1 year after surgery did not differ among patients undergoing DM and conventional THA; DM THA in particular was not associated with a higher risk of groin pain, despite its comparatively larger femoral head sizes. HR, on the other hand, was associated with a higher risk of pain. Appropriate implant sizing and bearing couple choice may optimize the functional benefit of THA. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11420-020-09764-6) contains supplementary material, which is available to authorized users.

Objective To identify the extent of hospital-to-hospital variation in use of obstetrical blood transfusion. Design Population-based cohort study linking provincial perinatal and blood transfusion registries. Setting British Columbia, Canada, 2004-2015. Population All pregnant women delivering at or beyond 20 weeks' gestation at any British Columbia hospital. Methods Mixed-effects regression models were used to estimate hospital-specific transfusion rates after sequentially accounting for (1) the role of random variation, (2) maternal medical and obstetrical characteristics (i.e. patient case mix) and (3) institutional and delivery factors (such as use of instrumental or caesarean delivery). Main outcome measures Hospital-specific use of obstetrical red blood cell transfusion. Results Among 44 hospitals, crude institutional transfusion rates across the study period ranged from 3.7 to 23.6 per 1000, with an average of 8.3 per 1000. After adjusting for maternal characteristics, institution and delivery risk factors, a nearly three-fold difference in rates between the 10th and 90th percentile remained (5.4-14.5 per 1000). Twelve sites had rates significantly higher or lower than the provincial average. Women residing in remote areas were 2.5-fold (95% CI 1.8-3.5] more likely to receive a blood transfusion than were women residing in metropolitan areas. Conclusions Meaningful variation between hospitals in use of blood transfusion during pregnancy was not explained by differences in patient case-mix or institutional factors, suggesting that over- or under-utilisation of this resource may be occurring in obstetrical care. Tweetable abstract Use of blood transfusion in pregnant women varied broadly between hospitals in British Columbia, Canada.

Smart grids integrate power system engineering with information and communication technology to form a complex system. In this study, a framework is proposed to model the smart grid as interdependent complex networks and investigate the topology vulnerabilities subject to targeted attacks. As a serious targeted cyber-physical threat, the load redistribution attack is a type of false data injection attack. Adversaries can intentionally intercept communication traffic flows or cooperatively manipulate data transmitted over the communication network to mislead the control centre to perform incorrect actions, thereby tripping off lines or breakers, and even triggering cascading failures. Based on the intelligent attack mechanism, a new approach is introduced to identify sequential attack targets according to the node importance, which can in turn collapse the entire power system. Based on the particular characteristics of power systems, the components require achieving a power balance through the redistribution or shedding of loads in each attack. Compared to random removal and block removal, the effectiveness of the proposed strategy was validated on the IEEE 39-bus and the actual provincial backbone network. From the analysis of the experimental results, we find that the topology vulnerability is closely related to the critical node types and locations.

Background STRIVE is a multicenter, observational, open-label, single-arm study of natalizumab in anti–JC virus (JCV) seronegative patients with early relapsing-remitting multiple sclerosis (RRMS). The objective of this prespecified 2-year interim analysis was to determine the effectiveness of natalizumab in establishing and maintaining no evidence of disease activity (NEDA) in early RRMS. Methods Patients aged 18–65 years had an RRMS diagnosis

Background Patient-reported outcome measures (PROMs) are being used increasingly to determine the success of total knee arthroplasty (TKA). Our goal is to investigate whether advanced age is associated with lower PROM scores. Methods We used our hospital’s TKA registry to examine the relationship between age and PROMs in all patients 50-90 years of age who underwent unilateral or simultaneous bilateral primary TKA between 2007 and 2011 with a primary diagnosis of osteoarthritis. All 5 domains of the Knee Injury and Arthritis Outcomes Score (KOOS) and the Lower Extremity Activity Scale (LEAS) at baseline, 2 years, and 5 years were collected. The association between age and PROM score was assessed by piecewise linear regression using generalized estimating equations, adjusting for demographics, comorbidity, and baseline score. Results Significant nonlinear relationships among age, KOOS subdomains, and LEAS were found. The placement of the age spline knot was at 70 years for KOOS Symptom and 68 years for KOOS Pain, KOOS Activities of Daily Living (ADL), and LEAS. The KOOS Symptom domain showed a significant worsening between 2-year and 5-year follow-up (P Conclusion We found an age-related decline in KOOS Pain, KOOS Symptom, KOOS ADL, and LEAS scores. The best fitting spline knots were at 68 (KOOS Pain, KOOS ADL, and LEAS) and 70 years (KOOS Symptoms), respectively. This demonstrates that there is a critical age at which functional decline begins regardless of the quality of the TKA surgery. Our findings will help surgeons accurately guide patient expectations after TKA based on age. Level of Evidence Level II, prognostic study.

Background: Clinical significance of germinal center B-cell (GCB) and non-GCB sub-categorization, expression of MYC, BCL2, BCL6, CD5 proteins and Epstein Barr virus encoded RNA (EBER) positivity in diffuse large B-cell lymphoma (DLBCL) remain controversial. Could these biomarkers accurately identify high risk DLBCL patients? Are MYC, BCL2 and BCL6 proteins expression feasible as baseline testing to predict c-Myc, BCL2 or BCL6 gene rearrangements? Aims: To investigate prognostic values of GCB/non-GCB sub-categorization, Double Protein Expression Lymphoma (DPL), Triple Protein Expression Lymphoma (TPL), positivity of CD5 protein and EBER in patients with DLBCL disease. To evaluate correlation between BCL2 , c-Myc and BCL6 gene rearrangements with BCL2, MYC and BCL6 proteins expression. Methods: Diagnostic tissue samples of 120 DLBCL patients between January 2012 to December 2013 from four major hospitals in Malaysia were selected. Samples were subjected to immunohistochemical staining, fluorescent in-situ hybridization (FISH) testing, and central pathological review. Pathological data were correlated with clinical characteristics and treatment outcome. Results: A total of 120 cases were analysed. Mean age of diagnosis was 54.1 years ± 14.6, 64 were males, 56 were females, mean follow up period was 25 months (ranged from 1 to 36 months). Of the 120 cases, 74.2% were non-GCB whereas 25.8% were GCB, 6.7% were EBER positive, 6.7% expressed CD5 protein, 13.3% were DPL and 40% were TPL. The prevalence of c-Myc, BCL2, BCL6 gene rearrangements were 5.8%, 5.8%, and 14.2%, respectively; and 1.6% were Double Hit Lymphoma (DHL). EBER positivity, DPL, TPL, c-Myc gene rearrangement, BCL2 gene rearrangement, extra copies of BCL2 gene and BCL6 gene rearrangement were associated with shorter median overall survival (P 0.05). Overall, c-Myc, BCL2 and BCL6 gene rearrangements showed weak correlation with expression of MYC, BCL2 and BCL6 proteins (P>0.05). Fluorescent in situ hybridization is the preferred technique for prediction of treatment outcome in DLBCL patients. Conclusion: c-Myc, BCL2, and BCL6 gene rearrangements, EBER expression, DHL, TPL and IPI score are reliable risk stratification tools. MYC, BCL2 and BCL6 proteins expression are not applicable as baseline biomarkers to predict c-Myc, BCL2, and BCL6 gene rearrangements.

Background The evolution of molecular studies in myeloproliferative neoplasms (MPN) has enlightened us the understanding of this complex disease consisting of polycythaemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). The epidemiology is well described in the western world but not in Asian countries like Malaysia. Materials and methods This retrospective national registry of MPN was conducted from year 2009 to 2015 in Malaysia. Results A total of 1010 patients were registered over a period of 5 years. The mean age was 54 years with male predominance. The ethnic distribution revealed that Chinese had a relatively high weighted incidence proportion (43.2%), followed by Indian (23.8%), Malay (15.8%) and other ethnic groups (17.2%). The types of MPN reported were 40.4% of ET (n = 408), 38.1% of PV (n = 385), 9.2% of PMF (n = 93), 3.1% of hypereosinophilic syndrome (HES) (n = 31) and 7.9% of unclassifiable MPN (MPN-U) (n = 80). Splenomegaly was only palpable clinically in 32.2% of patients. The positive JAK2 V617F mutation was present in 644 patients with 46.6% in PV, 36.0% in ET, 9.0% in PMF, and 7.4% in MPN-U, and had significantly lower haemoglobin (p

STRIVE was a 4-year, multicenter, observational, open-label, single-arm study of natalizumab treatment in anti-JC virus antibody-negative (JCV-negative) relapsing-remitting multiple sclerosis (RRMS) patients with disease duration ≤ 3 years. The objective of STRIVE was to examine no evidence of disease activity (NEDA) status and predictors of NEDA in natalizumab-treated patients with early RRMS.Proportions of patients with NEDA were evaluated along with baseline predictors of NEDA, annualized relapse rate, 24-week confirmed disability worsening (CDW), magnetic resonance imaging assessments (T2 and gadolinium-enhancing lesions), and serious adverse events.In years 1 and 2, 56.1% (95% confidence interval [CI] 48.7-63.4%) and 73.6% (95% CI 66.2-80.2%) of patients (intent-to-treat population [N = 222]), respectively, achieved NEDA. In years 3 and 4, 84.6% (95% CI 78.0-89.9%) and 91.9% (95% CI 86.4-95.8%) of patients, respectively, achieved Clinical NEDA (no relapses or 24-week CDW). Baseline predictors of NEDA in year 4 were Expanded Disability Status Scale score ≤ 2.0 (odds ratio [OR] = 3.85 [95% CI 1.54-9.63]; p = 0.004) and T2 lesion volume 4 cc (OR = 0.39 [95% CI 0.15-0.98]; p = 0.046), with the latter also predicting Clinical NEDA in year 4 (OR = 0.21 [95% CI 0.05-0.92]; p = 0.038). The cumulative probability of CDW at year 4 was 19.3%. Serious adverse events were reported in 11.3% of patients.These results support the long-term safety and effectiveness of natalizumab. Baseline predictors of NEDA help to inform benefit-risk assessments of natalizumab treatment in JCV-negative patients with early RRMS.ClinicalTrials.gov identifier NCT01485003.

Background: There is much advancement in treatment of chronic myeloid leukemia (CML) since the approval of first tyrosine kinase inhibitor (TKI), imatinib, by US FDA in 2001. One of them is definitely the concept of stopping TKI, starting at the CML patients who have achieved deep molecular response (MR) of MR4.5 for a reasonable long period of at least two years, pioneered by the researchers from French and Australia. Meanwhile, interferon, the standard treatment of CML before the era of TKI, showed that interferon-responded patients may indeed retain the response once interferon was withdrawn via interferon-induced immunity towards the leukemic clone. This is further supported by stop trial in Japan, in which after stopping TKI, interferon was given for 2 years and it showed a higher drug-free rate compared to stop trial from French and Australia. Hence, it is logical to postulate the use of interferon after TKI was stopped when patients have attained deep MR for more than two years will increase the percentage of patients remain TKI-free on follow-up. Materials and Methods: This is a multi-center randomized controlled trial. Adult CML patients, diagnosed in chronic phase, treated with ongoing TKI for at least 3 years without previous history of TKI failure and have achieved stable deep MR on International Scale for ≥2 years with at least 2 readings of MR4.5 (including the latest before study entry), were randomized into 2 arms: (1) peginterferon-α-2a, subcutaneous weekly, starting at 180 mcg, or (2) observation. Disease is monitored by PCR (centralized in Ampang Hospital) at monthly for the first year, 2 monthly for the second year and 3 monthly for the third year. Relapse is defined as either (i) one reading of loss of major MR, i.e. reading of >0.1% IS and confirmed by second analysis taken 1 month later if the first analysis point reading is ≤1% IS, or (ii) positivity of BCR-ABL1 transcripts, as confirmed by a second analysis point, indicating the increase (at least 1 log) in relation to the first analysis point at two successive assessments. Quality of Life is assessed using EORTC QLO-C30. Results: At the time of writing, total of 8 patients were randomized, 5 into peginterferon arm, 3 into observation arm, all were on imatinib, M:F = 4:4, Malay: Chinese:Indian = 3:4:1, median age 49.5 (range 25-58), median follow-up 4 months (range 1-6) and none of them relapse. Two patients developed imatinib withdrawal syndrome, both female on observation arm, one was mild and resolved after 2 months but one was severe and needed termination after 2 months and restarted on imatinib. Two patients in peginterferon arm developed mild hepatitis with liver enzymes

The archaic definition and registration processes for stillbirth currently prevalent in Canada impede both clinical care and public health. The situation is fraught because of definitional problems related to the inclusion of induced abortions at ≥20 weeks' gestation as stillbirths: widespread uptake of prenatal diagnosis and induced abortion for serious congenital anomalies has resulted in an artefactual temporal increase in stillbirth rates in Canada and placed the country in an unfavourable position in international (stillbirth) rankings. Other problems with the Canadian stillbirth definition and registration processes extend to the inclusion of fetal reductions (for multi-fetal pregnancy) as stillbirths, and the use of inconsistent viability criteria for reporting stillbirth. This paper reviews the history of stillbirth registration in Canada, provides a rationale for updating the definition of fetal death and recommends a new definition and improved processes for fetal death registration. The recommendations proposed are intended to serve as a starting point for reformulating issues related to stillbirth, with the hope that building a consensus regarding a definition and registration procedures will facilitate clinical care and public health.RéSUMé: La définition et les méthodes d’enregistrement archaïques des mortinaissances qui prévalent actuellement au Canada entravent à la fois les soins cliniques et la santé publique. La situation est délicate à cause des problèmes de définition que pose l’inclusion des avortements provoqués à ≥ 20 semaines de gestation parmi les mortinaissances : le recours généralisé au diagnostic prénatal et les avortements provoqués en cas d’anomalies congénitales graves ont entraîné une augmentation temporelle artéfactuelle des taux de mortinatalité au Canada et placé le pays dans une position défavorable dans les classements internationaux (de la mortinatalité). Les autres problèmes dans la définition et les méthodes d’enregistrement canadiennes des mortinaissances sont l’inclusion de la réduction fœtale (pour les grossesses multifœtales) parmi les mortinaissances et l’emploi de critères de viabilité inconsistants pour déclarer les mortinaissances. Nous examinons ici l’histoire de l’enregistrement des mortinaissances au Canada, nous justifions une révision possible de la définition de la mort fœtale et nous recommandons une nouvelle définition et des méthodes d’enregistrement améliorées des morts fœtales. Les recommandations proposées se veulent un point de départ à une reformulation des questions liées à la mortinatalité, dans l’espoir que l’établissement d’un consensus sur une définition et sur les méthodes d’enregistrement facilitera les soins cliniques et la santé publique.

BACKGROUND Blood transfusion is frequently used as an indicator of severe maternal morbidity during pregnancy. However, few studies have examined its validity in population perinatal databases. METHODS We linked a perinatal database from British Columbia, Canada, with the province's Central Transfusion Registry for 2004-2015 deliveries. Using the Central Transfusion Registry records for red blood cell transfusion as the gold standard, we calculated the sensitivity, specificity, positive predictive value, and negative predictive value of the perinatal database variable for red blood cell transfusion, overall and by transfusion risk factor status. We used multivariable logistic regression to examine whether outcome misclassification altered the odds ratios for different transfusion risk factors. RESULTS Among 473,688 deliveries, 4,033 (8.5 per 1,000) had a red blood cell transfusion according to the Central Transfusion Registry. The sensitivity of the perinatal database transfusion variable was 72.3 [95% confidence interval (CI) = 72.2, 72.4]. Sensitivity differed according to the presence of many transfusion risk factors (e.g., 84.9% vs. 72.2% in deliveries with versus without uterine rupture). Odds ratios associated with some transfusion risk factors were exaggerated when the perinatal database transfusion variable was used to define the outcome instead of the Central Transfusion Registry variable, but 95% confidence intervals for these estimates overlapped. CONCLUSION Blood transfusion was documented with reasonable sensitivity in this large population perinatal database. However, validity varied according to risk factor status. Our findings enable researchers to better account for outcome misclassification in studies of obstetrical transfusion risk factors.

INTRODUCTION Unfulfilled expectations, assessed postoperatively, have been consistently associated with dissatisfaction after total knee arthroplasty (TKA). However, identifying these expectations preoperatively has been a challenge. We aimed at identifying specific expectations that are most likely to affect postoperative dissatisfaction. METHODS We included all patients in our institutional registry with a body mass index of

The propagation of cascading failures of modern power systems is mainly constrained by the network topology and system parameter. In order to alleviate the cascading failure impacts, it is necessary to adjust the original network topology considering the geographical factors, construction costs and requirements of engineering practice. Based on the complex network theory, the power system is modeled as a directed graph. The graph is divided into communities based on the Fast&ndash, Newman algorithm, where each community contains at least one generator node. Combined with the islanding characteristics and the node vulnerability, three low-degree-node-based link-addition strategies are proposed to optimize the original topology. A new evaluation index combining with the attack difficulty and the island ratio is proposed to measure the impacts on the network under sequential attacks. From the analysis of the experimental results of three attack scenarios, this study adopts the proposed strategies to enhance the network connectivity and improve the robustness to some extent. It is therefore helpful to guide the power system cascading failure mitigation strategies and network optimization planning.

INTRODUCTION Socioeconomic factors such as poverty may mediate racial disparities in health outcomes after total hip arthroplasty (THA) and confound analyses of differences between blacks and whites. METHODS Using a large institutional THA registry, we built models incorporating individual and census tract data and analyzed interactions between race and percent of population with Medicaid coverage and its association with 2-year patient-reported outcomes. RESULTS Black patients undergoing THA had worse baseline and 2-year pain and function scores compared with whites. We observed strong positive correlations between census tract Medicaid coverage and percent living below poverty (rho = 0.69; P < 0.001). Disparities in 2-year Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function were magnified in communities with high census tract Medicaid coverage. For blacks in these communities, 2-year WOMAC function scores were predicted to be -5.54 points lower (80.42 versus 85.96) compared with blacks in less deprived communities, a difference not observed among whites. CONCLUSION WOMAC pain and function 2 years after THA are similar among blacks and whites in communities with little deprivation (low percent census tract Medicaid coverage). WOMAC function at 2 years is worse among blacks in areas of higher deprivation but is not seen among whites. LEVEL OF EVIDENCE Level II - Cohort Study.

Background Cognitive impairment affects many patients with multiple sclerosis (MS). NeuroTrax, a computerized cognitive screen that can be administered during routine clinical care, provides a consistent, validated, objective cognitive profile measure with a global cognitive score (GCS) and seven individual domain scores. Natalizumab is an efficacious therapy for relapsing MS, demonstrating reductions in disability worsening and MS disease activity measured by magnetic resonance imaging. Objective The aim of this study was to assess cognitive function as measured by NeuroTrax in MS patients treated with natalizumab for ≥ 2 years. Methods This retrospective observational study included adult MS patients in the United States who received 300 mg intravenous natalizumab every 4 weeks for ≥ 2 years. NeuroTrax data were evaluated at baseline and yearly thereafter. Changes in GCS and the seven individual cognitive domain scores from baseline to after 24 infusions of natalizumab were analyzed. Results In the study population at baseline (N = 52), 22 patients (42.3%) had disease duration of 0–5 years; 12 patients (23.1%) were treatment naive. GCS score improved significantly from baseline [mean 95.5, standard deviation (SD) 12.9] to year 2 (mean 98.9, SD 13.2; change from baseline 3.4; p = 0.003). After 2 years on natalizumab, 17 patients (32.7%) demonstrated clinically significant improvement (increase from baseline > 1 SD) in GCS. Results were similar regardless of whether patients had previously received MS therapy. Conclusions Patients treated with natalizumab demonstrated significant improvement in cognitive function, measured by NeuroTrax GCS, over 2 years of treatment.

ObjectivesTo estimate and compare the salivary cotinine levels using a semiquantitative method, called NicAlert, between three groups: non-smokers, daily smokers of cigarettes and daily smokers of midwakh, and to compare the carbon monoxide (CO) levels among these groups.Materials and methodsA total of 159 adult male volunteers aged 20 and above were included, with 54 current cigarette smokers, 52 current midwakh smokers and 53 non-smokers. Estimate of breath carbon monoxide and salivary cotinine were collected, as well as sociodemographic characteristics and details of smoking habits and second-hand smoke exposure among participants. Institutional review board approval was obtained and data were analysed using SPSS V.21 with the Kruskal-Wallis test used to obtain differences in the distribution.ResultsThere was no significant difference in the median breath CO and salivary cotinine levels between cigarette and midwakh smokers. Levels of breath CO were significantly higher in cigarette and midwakh smokers as compared with non-smokers (19.5, 17.5 and 6.0, respectively, pConclusionThese are the first data that we are aware of that demonstrate that in terms of at least two key biomarkers of tobacco use, there are comparable levels of exposure between cigarettes and midwakh users, demonstrating a need for intensified attention to the use of midwakh.

Objective To link the INTERGROWTH-21st gestational weight gain standard with the risks of excess maternal postpartum weight retention, approximated by women's weight change between successive pregnancies. Methods A population-based retrospective cohort study of 58,534 women delivering successive pregnancies in British Columbia, Canada (2000-2015) was conducted. Pregnancy weight gain (kg) in the index pregnancy was converted into a gestational age-standardized z-score using the INTERGROWTH-21st standard. Excess interpregnancy weight gain was defined as weight increases of 5 kg, 10 kg, or obesity (≥30 kg/m2) at the next pregnancy. Weight gain z-scores and excess interpregnancy weight change were associated using logistic regression. Results For all definitions of excess interpregnancy weight gain, risks remained low and stable below a weight gain z-score of 0 (50th percentile) but rose sharply with increasing z-scores above zero. Compared with women gaining −1 to 0 SD (16th to 50th percentiles), women gaining > 0 to +1 SD (51st to 84th percentiles) were 55% to 84% more likely to retain excess weight between pregnancies. Risks were three- to sixfold higher in women gaining >+1 SD. Conclusions A large range of the INTERGROWTH-21st percentiles were associated with increased risks of excess interpregnancy weight gain. The standard may normalize high weight gains of women at increased risk of excess weight retention.

Background Successful clinical outcomes following unicompartmental knee arthroplasty (UKA) depend on lower limb alignment, soft tissue balance and component positioning, which can be difficult to control using manual instrumentation. Although robotic-assisted surgery more reliably controls these surgical factors, studies assessing outcomes of robotic-assisted UKA are lacking. Therefore, a prospective multicenter study was performed to assess outcomes of robotic-assisted UKA. Methods A total of 1007 consecutive patients (1135 knees) underwent robotic-assisted medial UKA surgery from six surgeons at separate institutions between March 2009 and December 2011. All patients received a fixed-bearing metal-backed onlay implant as tibial component. Each patient was contacted at minimum two-year follow-up and asked a series of five questions to determine survivorship and patient satisfaction. Worst-case scenario analysis was performed whereby all patients were considered as revision when they declined participation in the study. Results Data was collected for 797 patients (909 knees) with average follow-up of 29.6 months (range: 22–52 months). At 2.5-years of follow-up, 11 knees were reported as revised, which resulted in a survivorship of 98.8%. Thirty-five patients declined participation in the study yielding a worst-case survivorship of 96.0%. Of all patients without revision, 92% was either very satisfied or satisfied with their knee function. Conclusion In this multicenter study, robotic-assisted UKA was found to have high survivorship and satisfaction rate at short-term follow-up. Prospective comparison studies with longer follow-up are necessary in order to compare survivorship and satisfaction rates of robotic-assisted UKA to conventional UKA and total knee arthroplasty.