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CADTH COVID News identifies emerging information on health technologies being investigated for the management or prevention of COVID-19. The intent is to provide a quick alert of a news item of interest and is only current as of posting. As research is rapidly evolving, CADTH will monitor these topics and update information as needed.
Updated on January 15, 2021 | 15:55am
Interleukin-6 Receptor Antagonists: Tocilizumab and Sarilumab
On January 7, 2021, preliminary results on the efficacy of interleukin-6 receptor antagonists in critically ill patients with COVID-19 were released in a pre-print (NCT02735707). The Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia (REMAP-CAP) is an ongoing international, open-label trial that enrolled patients with COVID-19 in an intensive care unit and receiving respiratory or cardiovascular organ support randomized to either tocilizumab (N = 353) or sarilumab (N = 48) or standard care (N = 402). The primary outcome was respiratory and cardiovascular organ support-free days measured up to day 21. Compared with standard care, the median adjusted odds ratios (primary model) were 1.64 (95% credible interval 1.25 to 2.14) for tocilizumab and 1.76 (95% credible interval 1.17 to 2.91) for sarilumab, yielding > 99.9% and 99.5% posterior probabilities of superiority. Caution should be exercised in interpreting any preliminary study results. Furthermore, this pre-print has not been peer-reviewed.
On December 17, 2020, results of the phase III, randomized, double-bind, placebo-controlled, multi-centre study EMPACTA (Evaluating Minority Patients with Actemra) were published (NCT04372186). The EMPACTA study enrolled hospitalized patients with COVID-19 pneumonia not receiving mechanical ventilation who underwent randomization to standard care plus tocilizumab (N = 259) or placebo (N = 129). The primary efficacy outcome was mechanical ventilation or death by day 28. The hazard of death was lower in the standard care plus tocilizumab group compared to placebo (hazard ratio 0.56, 95% confidence interval 0.33 to 0.97).
A CADTH technology review on interleukin-6 receptor therapies in managing COVID-19 is in progress.
Updated on November 25, 2020 | 4:15pm
On November 19, 2020, early results of REMAP-CAP — a trial investigating tocilizumab to treat critically ill patients with severe COVID-19 — were announced. REMAP-CAP is a randomized, embedded, multifactorial, adaptive, platform trial evaluating various treatments in adult patients with community-acquired pneumonia admitted to an intensive care unit (ICU) (NCT02735707). As a sub-platform of REMAP-CAP, REMAP-COVID is evaluating treatments that are specific to COVID-19. The trial results provided so far were based on the first 303 patients randomized to tocilizumab, sarilumab, anakinra, interferon, or no immunomodulator. It showed that patients with severe COVID-19 in the ICU treated with tocilizumab were more likely to have improved outcomes (measured by a combination of organ support, such as a breathing machine, in the ICU and surviving the hospital admission) compared with patients not receiving an immunomodulator (odds ratio = 1.87). No other details were released and the results have not been published in a peer-reviewed journal. Caution is therefore required in interpreting these results.
Updated on October 23, 2020 | 1:15pm
On October 20, 2020, two randomized controlled trials (RCTs) of tocilizumab for the treatment of COVID-19 were published. The CORIMUNO-19-TOCI-1 trial is a multi-centre, open-label RCT that compared tocilizumab plus standard of care (SoC) to SoC alone for the treatment of patients hospitalized with COVID-19 pneumonia requiring oxygen but not ventilation, and had a World Health Organization Clinical Progression Scale (WHO-CPS) score of 5. There were 130 patients included from nine centres in France. There were two primary end points: the proportion of patients with scores higher than 5 on the WHO-CPS on day 4, and survival without need for ventilation at day 14. The proportion of patients achieving a WHO-CPS score greater than 5 at day 4 did not meet the 95% pre-specified efficacy threshold for negative absolute risk difference. A total of 24% of patients in the tocilizumab plus SoC group and 36% of patients in the SoC alone group required ventilation or died by day 14 (median posterior hazard ratio: 0.58; 90% credible interval, 0.33 to 1.00), with a posterior probability of a hazard ratio of less than 1 of 95.05%. This met the pre-specified efficacy threshold of greater than 95%. There were 44% patients in the tocilizumab plus SoC group and 54% in the SoC alone group who experienced adverse events.
The RCT-TCZ-COVID-19 trial is a multi-centre, open-label RCT that compared tocilizumab to SoC for the treatment of patients hospitalized with COVID-19 who required oxygen by nasal cannula but did not require intensive care unit (ICU)-level care and were still eligible to receive ICU treatment. There were 126 patients included from 24 centres in Italy. The primary end point was a composite of the development of a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen of less than 150 mm Hg, ICU admission, or death. The trial was terminated early for futility, as there was no difference between the groups in the primary end point. There were more adverse events in the tocilizumab group (23%) than in the standard care group (11%).
On October 21, 2020 a third RCT of tocilizumab was published. The BACC Bay Tocilizumab Trial is a double-blind, placebo-controlled RCT that compared tocilizumab to placebo for patients hospitalized with COVID-19 and who may have been receiving oxygen but not ventilation. There were 243 patients included from seven centres in the US. There was no difference between the groups in the primary end point, which was intubation or death. There was more neutropenia in the tocilizumab group than in the placebo group but fewer serious infections.
CADTH completed a Health Technology Review on tocilizumab (August 25, 2020), and will continue to monitor the emerging evidence related to this drug for managing COVID-19.
Updated on September 23, 2020 | 4:55pm
On September 18, 2020, a press release was made available about the results of a study of tocilizumab for the treatment of COVID-19 (EMPACTA, NCT04372186). A multi-centre, randomized, double-blind, placebo-controlled trial that compared tocilizumab to placebo (in addition to standard of care) for the treatment of patients hospitalized with COVID-19 pneumonia was conducted. There were 389 patients enrolled from the US, South Africa, Kenya, Brazil, Mexico, and Peru. The primary end point — progression to mechanical ventilation or death by day 28 — occurred in 12.2% in the tocilizumab arm versus 19.3% in the placebo arm. The hazard ratio was 0.56; 95% confidence interval: 0.32 to 0.97. There was no statistically significant difference between the groups for time to hospital discharge, time to improvement, time to clinical failure, or mortality. Common adverse events reported included constipation, anxiety, and headache. Until the full study results are published in a peer-reviewed journal, no conclusions can be drawn from this information.
Updated on September 9, 2020 | 11:18am
CADTH completed a Horizon Scan on sarilumab, and will continue to monitor the emerging evidence related to this drug for managing COVID-19.
CADTH completed a Health Technology Review on tocilizumab, and will continue to monitor the emerging evidence related to this drug for managing COVID-19.
Updated on July 27, 2020 | 13:30pm
Tocilizumab, an interleukin-6 receptor antagonist, is indicated for cytokine release syndrome and for various rheumatological disorders in Canada. A phase III international trial, COVACTA (including Canadian sites) is under way investigating tocilizumab compared to placebo in patients with COVID-19 (NCT04320615). Randomized controlled trials are ongoing and CADTH will continue to monitor the emerging evidence related to interleukin-6 receptor antagonists in COVID-19.
Sarilumab is an interleukin-6 receptor antagonist indicated for rheumatoid arthritis in Canada and has been identified as a potential option to treat COVID-19. On July 2, 2020, the phase III cohort 2 (NCT04315298) of patients with COVID-19 that required mechanical ventilation failed to meet primary and key secondary end points and the trial was stopped. There are ongoing randomized controlled trials investigating sarilumab monotherapy versus placebo or standard of care for the treatment of COVID-19. CADTH will continue to monitor emerging evidence related to interleukin-6 receptor antagonists in COVID-19.
Updated on December 9, 2020 | 15:55am
Health Canada Authorizes Pfizer-BioNTech COVID-19 Vaccine, Tozinameran (BNT162b2)
On December 9, 2020, Health Canada issued an authorization with conditions under the COVID-19 Interim Order for the mRNA-based Pfizer-BioNTech COVID-19 Vaccine, Tozinameran. It is indicated for use in Canada in individuals 16 years of age and older to prevent COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The vaccine is administered intramuscularly in two doses, 21 days apart. The recommended storage temperature is ‒70⁰ C (plus or minus 10 degrees for up to 10 days unopened). Efficacy and safety data were based on two ongoing clinical trials (phase I/II Study BNT162-01 NCT04380701, phase I/II/III Study C4591001 NCT04368728). Interim results for NCT04368728 were reported in a previous news update on this page. More information is available in the Regulatory Decision Summary and Product Monograph. The Government of Canada previously announced an agreement to secure up to 20 million doses of the Pfizer-BioNTech vaccine and recently announced that it will receive up to 249,000 initial doses in December 2020.
Updated on November 13, 2020 | 7:40am
COVID-19 Vaccine Candidate: BNT162b2
On November 9, 2020, a press release was made available about the first interim analysis results of an mRNA-based COVID-19 vaccine candidate, BNT162b2. Of the 43,538 participants enrolled in this phase III, randomized, placebo-controlled, observer-blind trial (NCT04368728), 38,955 participants had received a second dose of the vaccine as of November 8, 2020. The first interim efficacy analysis conducted on November 8, 2020, comprised 94 confirmed cases of COVID-19 that showed a vaccine efficacy rate above 90% seven days following the second dose. Caution should be exercised in interpreting any interim study results. The trial will continue until a final analysis with an accrued total of 164 confirmed cases of COVID-19. In August 2020, the Government of Canada signed an agreement with Pfizer to supply a minimum of 20 million doses of the mRNA-based vaccine candidate, BNT162. However, Health Canada will need to assess its safety and efficacy before it becomes available to Canadians.
Updated on December 9, 2020 | 13:45pm
COVID-19 Vaccine Candidate: ChAdOx1 nCoV-19 (AZD1222)
On November 19, 2020, preliminary findings of a single-blind, randomized, controlled, phase II/III trial (NCT04400838) investigating the adenovirus-vectored vaccine ChAdOx1 nCoV-19 compared to a control vaccine, MedACWY, were published. The early results are based on the phase II component including a total of 560 patients enrolled in the UK, aged 18 years and older. Participants were stratified by age (18 to 55, 56 to 69, 70 years and older), dose group (low dose, standard dose), and study site. The co-primary outcomes in this ongoing trial are efficacy (symptomatic confirmed COVID-19 cases) and safety (serious adverse events); however, these preliminary results report on select secondary end points. The authors reported that, in all age groups, those who received two standard doses of ChAdOx1 nCoV-19 had similar immunogenicity (median anti-spike severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] IgG responses, neutralizing antibody titres) and that the older age group appeared to be better able to tolerate the doses. However, the full results of this ongoing trial will be important to understand the impact of ChAdOx1 nCoV19 on confirmed cases of symptomatic COVID-19.
Updated on November 26, 2020 | 12:15pm
SARS-CoV-2 Neutralizing Antibodies: Casirivimab and Imdevimab (REGN-COV2)
On November 21, 2020, the US FDA issued an emergency use authorization for REGN-COV2 to treat high-risk patients with mild to moderate COVID-19. This therapy (REGN-COV2) consists of a combination of virus-specific casirivimab and imdevimab monoclonal antibodies given intravenously. The FDA based its decision on results from 799 non-hospitalized adults with recently diagnosed mild to moderate COVID-19 symptoms who were enrolled in a randomized, double-blind, placebo-controlled clinical trial (NCT04425629). Preliminary results on the primary end point of viral load were provided in the news item that follows. The FDA reported that hospitalizations and emergency room visits occurred in 3% of antibody-treated patients compared to 9% in placebo-treated patients, within 28 days after treatment. No other data were provided and the results of the trial have not been published in a peer-reviewed journal. It is important to mention that this treatment was not authorized for more severe disease; that is, in patients who are hospitalized due to COVID-19 or require oxygen therapy due to COVID-19. At this time, REGN-COV2 has not been approved for use in Canada.
On October 28, 2020, preliminary results were announced from a US study investigating REGN-COV2 (a combination of the monoclonal antibodies REGN10933 and REGN10987) for the treatment of COVID-19 in outpatients who are symptomatic or asymptomatic. This study (NCT04425629) is a phase II/III randomized, double-blind, placebo-controlled trial to evaluate REGN-COV2 administered intravenously. The study is expected to ultimately include more than 2,000 patients. The preliminary results included 524 patients; results for the first 275 patients were previously released. The primary end point — the average daily change in viral load through day 7 (mean time-weighted average change from baseline) — was statistically significantly lower in the REGN-COV2 group compared with the placebo group. The mean time-weighted average change in viral load from baseline through day 7 in patients with a detectable viral load at baseline was a 0.36 log10 copies/mL greater reduction with REGN-COV2 compared with placebo (P = 0.0003 for both dose groups). These results should be interpreted with caution until the full study results are published in a peer-reviewed journal.
CADTH will continue to monitor the emerging evidence related to SARS-CoV-2 neutralizing antibodies in managing COVID-19.
Inhaled Interferon Beta-1a, SNG001
On November 12, 2020, the results of a multi-centre, phase II, randomized, double-blind, placebo-controlled trial (NCT04385095) that compared an inhaled interferon beta-1a formulation, SNG001, against placebo were published. The study was conducted across nine sites in the UK that included 101 hospitalized patients with confirmed severe acute respiratory syndrome coronavirus 2 — SARS-CoV-2 — infection. The primary end point was defined as the change in clinical condition using the WHO Ordinal Scale for Clinical Improvement (OSCI) during the treatment period assessed in the intention-to-treat population. For the OSCI outcome, the treatment period encompassed 16 days, which included a 14-day dosing period and an end-of-treatment visit on day 15 or day 16. The odds of improvement on the OSCI were higher in patients who received SNG001 than in the placebo group on day 15 or 16 (odds ratio = 2.32, 95% confidence interval 1.07 to 5.04). CADTH will continue to monitor the emerging evidence related to SNG001 in managing COVID-19.
Updated on September 1, 2020 | 12:55pm
Interferon Beta-1a
Interferon beta-1a is an immunomodulator indicated in Canada for the treatment of multiple sclerosis. On August 20, 2020, a small, single-centre (Iran), open-label randomized controlled trial was published comparing interferon beta 1a to standard of care for patients hospitalized with COVID-19. There was no statistical difference between the treatment groups in terms of the primary outcome of the time to clinical response. There are ongoing trials investigating different types of interferons for the treatment of COVID-19. CADTH will continue to monitor the emerging evidence related to interferon beta-1a in managing COVID-19.
On November 19, 2020, the US FDA issued an emergency use authorization (EUA) for baricitinib in combination with remdesivir for the treatment of suspected or laboratory-confirmed COVID-19 in hospitalized adults and pediatric patients two years and older with the following criteria: requiring supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation. This EUA was based on a multi-centre, adaptive, phase III, randomized, double-blind, placebo-controlled trial, ACTT-2 (NCT04401579); an existing FDA-approved indication of baricitinib for rheumatoid arthritis (NDA 207924); and data assessed in populations for other indications. The preliminary results of ACTT-2 were previously reported by CADTH in the news item that follows.
Updated on October 9, 2020 | 11:40am
Baricitinib is a Janus kinase (JAK) inhibitor, a selective immunosuppressant, indicated in Canada for the treatment of rheumatoid arthritis. On October 8, 2020, preliminary results of the Adaptive COVID-19 Treatment Trial (ACTT-2) sponsored by the National Institute of Allergy and Infectious Diseases (NIAID) for the treatment of COVID-19 were released. The phase III study is a multi-centre, adaptive, randomized, double-blind, placebo-controlled trial where new arms can be added over time; the trial will compare different therapies to standard of care in patients hospitalized with COVID-19. The results described here compare baricitinib plus remdesivir versus remdesivir alone (in addition to standard of care). The primary end point — median days to recovery (defined as being well enough for hospital discharge) — was seven days in the baricitinib plus remdesivir arm versus eight days in the remdesivir only arm, incidence rate ratio: 1.16; 95% confidence interval, 1.01 to 1.32. Although safety information for ACTT-2 was not reported as part of the preliminary results, serious infections, thrombosis, malignancies, and other adverse effects have been reported with the use of baricitinib. Until the full study results are published in a peer-reviewed journal, no conclusions can be drawn from this information. CADTH will continue to monitor the emerging evidence related to baricitinib in managing COVID-19.
Updated on November 25, 2020 | 11:55am
SARS-CoV2 Neutralizing Antibody: Health Canada Authorizes Bamlanivimab With Conditions
On November 20, 2020, Health Canada issued an authorization for bamlanivimab, with conditions, under the COVID-19 Interim Order for use in the treatment of patients 12 years of age or older who weigh 40 kg or more, with mild to moderate COVID-19, and who are at high risk of progressing to severe COVID-19 illness and/or hospitalization. This decision was based on the interim analysis results of BLAZE-1 (NCT04427501). These results are reported in the previous news item posted on October 30, 2020. CADTH is conducting a Focused Critical Appraisal of the published interim analysis of the BLAZE-1 study.
SARS-CoV-2 Neutralizing Antibodies: FDA issues EUA for bamlanivimab
On November 9 2020, the US FDA issued an emergency use authorization (EUA) for the investigational monoclonal antibody therapy bamlanivimab (also known as LY-CoV555) for the treatment of patients with mild-to-moderate COVID-19 who are 12 years of age and older and weigh at least 40 kg, and who are at high risk for progressing to severe COVID-19 and/or hospitalization. While the evaluation of the efficacy and safety of bamlanivimab is ongoing, interim results from BLAZE-1 (NCT04427501), published on October 28, 2020, described in a previous news item below, formed the basis for this decision. In Canada, an application for authorization of bamlanivimab was filed on October 12, 2020, and is currently under review by Health Canada.
On October 28, 2020, results from the preplanned interim analysis of the bamlanivimab monotherapy arms of the BLAZE-1 study were published. The BLAZE-1 study (NCT04427501) is a US-based, multi-centre, randomized, double-blind, placebo-controlled phase II study to evaluate the SARS-CoV-2 neutralizing antibodies bamlanivimab (also known as LY-CoV555 or LY3819253) and etesevimab (also known as LY-CoV016) for the treatment of outpatients with mild or moderate symptoms of COVID-19. The results reported in this publication are for 452 patients who received one of three doses of bamlanivimab (700 mg, 2,800 mg, or 7,000 mg) or placebo. The primary end point was change from baseline in viral load at day 11. A statistically significant difference in the decrease from baseline viral load compared with placebo was observed for the 2,800 mg dose, but not for the 700 mg or 7,000 mg doses. The authors caution that viral load at day 11 may not be a clinically meaningful end point because viral load was reduced from baseline in all patients, including those receiving placebo. Caution should be exercised in interpreting any interim study results. The BLAZE-1 study is ongoing with an anticipated study completion date of January 15, 2021.
On October 26, 2020, the National Institute of Health (NIH) announced that the LY-CoV555 (also known as bamlanivimab or LY3819253) substudy of the ACTIV-3 trial for the treatment of COVID-19 would no longer be recruiting patients due to a low likelihood of efficacy. The ACTIV-3 trial (NCT04501978) is a multi-centre, randomized, double-blind, placebo-controlled phase III trial with an adaptive design to evaluate different therapeutic agents (in addition to the standard of care, including remdesivir), for the treatment of COVID-19 in hospitalized patients. The primary study end point was clinical response using an ordinal scale at day 5. The ACTIV-3 trial is adaptive, so additional arms will open with other drugs, with an expected sample size of 10,000. Until the full study results are published in a peer-reviewed journal, no conclusions can be drawn from this information. ACTIV-3 is part of the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) program of the NIH.
Bamlanivimab and Etesevimab: SARS-CoV-2 Neutralizing Antibodies
On October 7, 2020, interim analysis results were released from a US study of the SARS-CoV-2 neutralizing antibodies LY-CoV555 (bamlanivimab) and LY-CoV016 (etesevimab) for the treatment of COVID-19. BLAZE-1 (NCT04427501) is a multi-centre, randomized, double-blind, placebo-controlled phase II study to evaluate bamlanivimab and etesevimab (administered intravenously) for the treatment of outpatients with mild or moderate symptoms of COVID-19 and a positive SARS-CoV-2 test within three days of infusion. The study is expected to have 800 patients across all treatment arms, including three monotherapy bamlanivimab arms, one combination bamlanivimab and etesevimab arm, and a placebo arm. The interim analysis included results from 268 patients who participated in the combination bamlanivimab and etesevimab arm and the placebo arm. The primary end point — viral load at day 11 — was statistically significantly reduced in patients in the bamlanivimab and etesevimab arm compared with those in the placebo arm, although specific data were not reported. Caution should be exercised in interpreting any interim study results. The BLAZE-1 study is ongoing, and until the full study results are published in a peer-reviewed journal, no conclusions can be drawn from this information.
On November 20, 2020, WHO issued a conditional recommendation against the use of remdesivir in patients hospitalized with COVID-19, regardless of disease severity. This conditional recommendation was developed as there is currently no evidence that remdesivir improves survival and other outcomes in these patients. An international guideline development group comprised of 28 clinical care experts, four patient-partners, and one ethicist reviewed the interim results of the WHO Solidarity Trial along with three other randomized controlled trials that informed this conditional recommendation. Overall, the international expert panel identified that further research with more robust evidence in specific groups of patients is needed. CADTH will continue to monitor the emerging evidence related to remdesivir in COVID-19.
Updated on November 6, 2020 | 10:20pm
CADTH assessed four randomized controlled trials as part of a health technology review on remdesivir which includes the final published results of ACTT-1. On October 9, 2020, final results of the phase III, adaptive, international, double-blind, placebo-controlled Adaptive COVID-19 Treatment Trial (ACTT-1) (N = 1, 062) were published. In ACTT-1, remdesivir was compared with placebo in hospitalized adults with a confirmed diagnosis of COVID-19 and with evidence of a lower respiratory tract infection. Approximately 90% of patients had severe disease. The primary outcome was the time to recovery during the 28 days after enrolment (based on meeting criteria for category 1, 2, or 3 on an eight-category ordinal scale). The median time to recovery was shorter in patients who received remdesivir than with placebo (10 days versus 15 days), with a statistically significant rate ratio for recovery of 1.29 (95% confidence interval, 1.12 to 1.49). Mortality over the entire study period was not different between remdesivir and placebo, based on Kaplan–Meier estimates. CADTH will continue to monitor the emerging evidence related to remdesivir in COVID-19 and update the health technology review on remdesivir to include the published results of ACTT-1.
On October 22, 2020, the US FDA approved remdesivir in adults and pediatric patients 12 years and older for the treatment of COVID-19 requiring hospitalization. Previously, the FDA issued Emergency Use Authorizations on May 1, 2020, and on August 28, 2020 for hospitalized patients with severe disease and moderate disease, respectively. Remdesivir has been approved in Canada since July 27, 2020 when Health Canada issued a Notice of Compliance with conditions to use remdesivir for the treatment of severe COVID-19 in adults and adolescents 12 years and older who have pneumonia and require supplemental oxygen therapy. CADTH will continue to monitor the emerging evidence related to remdesivir in managing COVID-19.
On October 9, 2020, final results of the phase III, adaptive, international, double-blind, placebo-controlled Adaptive COVID-19 Treatment Trial (ACTT-1) (N = 1, 062) were published. In ACTT-1, remdesivir was compared with placebo in hospitalized adults with a confirmed diagnosis of COVID-19 and with evidence of a lower respiratory tract infection. Approximately 90% of patients had severe disease. The primary outcome was the time to recovery during the 28 days after enrolment (based on meeting criteria for category 1, 2, or 3 on an eight-category ordinal scale). The median time to recovery was shorter in patients who received remdesivir than with placebo (10 days versus 15 days), with a statistically significant rate ratio for recovery of 1.29 (95% confidence interval, 1.12 to 1.49). Mortality over the entire study period was not different between remdesivir and placebo, based on Kaplan–Meier estimates. CADTH will continue to monitor the emerging evidence related to remdesivir in COVID-19 and update the health technology review on remdesivir to include the published results of ACTT-1.
CADTH assessed four randomized controlled trials as part of a health technology review on remdesivir. On August 21, 2020, the results of the phase III, international, multi-centre, open-label, randomized controlled GS-US-540-5774 study were published that compared patients with moderate COVID-19 who received remdesivir (five-day course or 10-day course), with standard of care alone. The odds of improvement in clinical status at day 11 was statistically significantly higher in the five-day remdesivir group compared with the standard of care group (odds ratio = 1.65; 95% confidence interval 1.09 to 2.48, P = 0.02). However, there was no statistical difference in the odds of improvement in clinical status between the 10-day remdesivir group compared with standard of care. CADTH will continue to monitor the emerging evidence related to remdesivir in COVID-19.
Updated on July 30, 2020 | 4:37pm
Remdesivir is an antiviral medication that is the first drug approved by Health Canada for COVID-19. This decision was issued on July 27, 2020 and is an authorization with conditions to prescribe remdesivir for the treatment of COVID-19 in patients with pneumonia who require oxygen therapy. CADTH assessed four randomized controlled trials as part of a health technology review on remdesivir and will continue to monitor the emerging evidence related to remdesivir in COVID-19.
Fluvoxamine is a selective serotonin reuptake inhibitor indicated in Canada for depression and obsessive-compulsive disorder. On November 12, 2020, preliminary results of the STOP COVID study (NCT04342663) were published. This phase II, single-centre, randomized, double-blind, placebo-controlled trial included 152 adult outpatients with confirmed SARS-CoV-2 infection, symptoms of COVID-19 within seven days of the first dose of the trial medication, and an oxygen saturation of 92% or greater. Patients were administered fluvoxamine titrated to 100 mg three times daily for 15 days (80 patients) or a matching placebo capsule (72 patients). The primary outcome was clinical deterioration (shortness of breath or hospitalization for shortness of breath or pneumonia, and oxygen saturation less than 92% on room air or a need for supplemental oxygen to achieve an oxygen saturation of 92% or greater) occurring within 15 days of randomization. Of the 115 patients who completed the trial, clinical deterioration occurred in six of 72 patients in the placebo group and none of the patients in the fluvoxamine group. The absolute difference was 8.7% (95% confidence interval 1.8% to 16.4%, P = 0.009). This trial is limited by its small sample size and short follow-up time. Larger trials are required to confirm the findings of this study.
COVID-19 Vaccine Candidate: mRNA-1273
On November 16, 2020, Moderna Inc. announced interim analysis results of their COVID-19 vaccine candidate, mRNA-1273. The phase III, randomized, stratified, observer-blind, placebo-controlled trial (NCT04470427) enrolled 30,000 participants in the US. In the first interim efficacy analysis, 95 confirmed cases of COVID-19 were observed, with 90 cases in the placebo group and five cases in the vaccine group, which translated into an efficacy rate of 94.5% (P < 0.0001). Caution should be exercised in interpreting any interim study results. An application will be filed with the FDA to request emergency use authorization when they reach 151 confirmed cases of COVID-19 with a median follow-up of more than two months. The Government of Canada has signed an agreement with Moderna Inc. to supply 56 million doses of its vaccine. Health Canada will be required to assess its safety and efficacy before it becomes available to Canadians.
COVID-19 Vaccine Candidate: Sputnik V (Gam-COVID-Vac)
On November 11, 2020, interim analysis results from a phase III, randomized, double-blind, placebo-controlled trial (NCT04530396) showed that Sputnik V (also called Gam-COVID-Vac), a two-dose COVID-19 vaccine candidate, was 92% effective based on 20 confirmed cases of COVID-19. This interim analysis was performed 21 days after the first injection. More than 20,000 participants have been vaccinated with a first dose and 16,000 participants have had a second dose of the vaccine. Caution should be exercised in interpreting any interim study results. Initial phase I/II trial results published in The Lancet on September 26, 2020 prompted the Russian government to issue an Emergency Use Authorization on August 11, 2020.
Government of Canada: Preliminary Guidance on Early COVID-19 Immunization
On November 3, 2020, the National Advisory Committee on Immunization, an advisory body to the Public Health Agency of Canada, published a preliminary guidance policy for the allocation of the COVID-19 vaccine. Initial vaccine supply may be limited and will require the prioritization of its early administration. Key populations identified for early immunization include: individuals with advanced age or other high-risk conditions; health care workers, personal care workers, and caregivers in long-term care facilities for seniors; workers managing the COVID-19 response or providing frontline care for COVID-19 patients; essential service workers; household contacts of those at risk of severe illness or death from COVID-19; and those at high risk due to their living or working conditions where an infection could have disproportionate consequences. The recommendations are based on evidence to date. This guidance may change as new evidence becomes available regarding the characteristics of the vaccine, the clinical trial data, and the availability of the supply.
Updated on October 27, 2020 | 10:55am
On October 20, 2020, the results of a randomized controlled trial of convalescent plasma in the management of moderate COVID-19 (PLACID) were published. The PLACID trial is an open-label phase II, multi-centre, randomized controlled trial for patients hospitalized with moderate COVID-19. There were 464 patients included from 39 hospitals in India. There was no statistically significant difference between the treatment groups in terms of the primary outcome of a composite of a progression to severe disease, or 28-day mortality; 19% in the convalescent plasma group and 18% in the standard of care group experienced this outcome by day 28. There are ongoing trials investigating convalescent plasma for the treatment of COVID-19. CADTH has previously reported on the evidence evaluating the use of convalescent plasma for managing COVID-19, and will continue to monitor this evidence.
Updated on August 25, 2020 | 10:45am
On August 19, 2020, the FDA's plan to issue an emergency authorization for convalescent plasma to treat COVID-19 was put on hold due to emerging data. However, the FDA has now (on August 23, 2020) issued an emergency use authorization (EUA) for investigational convalescent plasma to treat patients hospitalized with suspected or laboratory-confirmed COVID-19. Although clinical trials on the efficacy and safety of convalescent plasma for the treatment of COVID-19 remain ongoing, the FDA's EUA is based on an extensive review of available evidence and is meant to facilitate emergency access to convalescent plasma treatment for patients with COVID-19.
Updated on August 21, 2020 | 3:35pm
On August 19, 2020, it was reported that the FDA's plan to issue an emergency authorization for convalescent plasma to treat COVID-19 has been put on hold. This decision was reportedly based on emerging data from a study involving patients hospitalized with severe COVID-19, who were participating in a US-based Expanded Access Program (n = 35,322). In this study (currently released in preprint), the authors reported that plasma transfusion within three days of a COVID-19 diagnosis was associated with lower seven-day and 30-day mortality rates compared with plasma transfusion four or more days after a COVID-19 diagnosis. However, this study was not randomized and has not been peer-reviewed. In Canada, access to convalescent plasma is currently only available through participation in clinical trials and is the responsibility of Canadian Blood Services and Héma-Québec. CADTH has conducted a Technology Review of convalescent plasma for COVID-19 and will update this report on a monthly basis as data continue to emerge.
Intravenous Immune Globulin
Intravenous immune globulin (IVIG) is a concentrated form of human immune globulin produced from donor plasma that is indicated in Canada for several immune-mediated conditions. On October 21, 2020 the results of a randomized controlled trial were published evaluating IVIG for the treatment of patients hospitalized with severe COVID-19. The trial is a randomized, double-blind, placebo-controlled trial conducted at a single centre in Iran. There were 59 patients included in the trial. Although this trial is a pilot study and authors do not state what the primary study outcome is, the in-hospital mortality rate in the IVIG group was 20%, with 48% in the placebo group (P = 0.022). CADTH has produced a report, Ongoing Trials of Plasma-Based Therapies for the Treatment of COVID-19 (updated on September 24, 2020), and will continue to monitor emerging evidence for the use of plasma products, including IVIG for the treatment of COVID-19.
WHO Solidarity Trial: Remdesivir, Lopinavir/Ritonavir, Hydroxychloroquine, Interferon Beta-1a
On October 15, 2020, interim study results from the World Health Organization's Solidarity Trial were released in pre-print (ISRCTN83971151). The Solidarity Trial is a large, international, adaptive, open-label, randomized controlled trial launched by the World Health Organization and other partners to evaluate several treatments for COVID-19. The interim results report on the findings of four separate treatments compared with local standard of care in hospitalized patients with COVID-19: remdesivir, lopinavir and ritonavir, interferon beta-1a, and hydroxychloroquine. The primary outcome was in-hospital mortality. The intention-to-treat analyses included 11,255 patients enrolled from 405 hospitals in 30 countries, including Canada. No treatment had a statistically significant reduction in 28-day in-hospital mortality compared with its control. Caution should be exercised in interpreting any interim study results. In addition, pre-print reports have not been peer-reviewed. Publication of full study results in a peer-reviewed journal are pending.
Lopinavir-ritonavir
On October 5, 2020, the results of the lopinavir-ritonavir arm of the Randomised Evaluation of Covid-19 therapy (RECOVERY) trial were published. The RECOVERY trial is a large open-label randomized controlled platform trial including several investigational arms for patients hospitalized with COVID-19 in the UK. This paper reports the comparison between lopinavir-ritonavir in addition to standard of care (1,616 patients) and standard of care alone (3,424 patients). There was no statistical difference between the treatment groups in terms of the primary outcome of 28-day mortality; 23% in the lopinavir-ritonavir group and 22% in the standard of care group died by day 28. There were no differences between groups for any pre-specified subgroup analyses, or for any secondary end points (time to hospital discharge, proportion of patients discharged from hospital, and a composite of invasive mechanical ventilation or death for those who did not start the study on mechanical ventilation). CADTH has previously reported on the evidence evaluating the use of lopinavir-ritonavir for managing COVID-19.
CADTH has completed a Health Technology Review on lopinavir-ritonavir and will continue to monitor the emerging evidence related to this drug combination for managing COVID-19
The co-formulation of lopinavir-ritonavir is an antiretroviral drug indicated for the treatment of HIV-1 in Canada . There are published and ongoing randomized controlled trials investigating lopinavir-ritonavir to potentially manage COVID-19. On June 29, 2020, the RECOVERY study Steering Committee discontinued randomization in the lopinavir-ritonavir treatment arm based on no benefit. On July 4, 2020, the Solidarity Trial established by WHO discontinued the lopinavir-ritonavir treatment arm due to a lack of efficacy. CADTH will continue to monitor emerging evidence related to antiretroviral drugs in COVID-19.
COVID-19 Rapid Antigen Testing Device: PANBIO COVID-19 Antigen Rapid Test
On October 5, 2020, Health Canada authorized the Abbott Rapid Diagnostics PANBIO COVID-19 Ag antigen testing rapid test device. The Panbio COVID-19 Ag is the first antigen test authorized by Health Canada for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The device is authorized for use at the point of care and can be administered by trained professionals outside of a laboratory in settings like pharmacies, walk-in clinics, or doctors' offices. The test can provide results in less than 20 minutes. The Government of Canada has arranged to procure up to 20.5 million of the rapid antigen tests. Additional point-of-care rapid antigen tests for SARS-CoV-2 are currently under evaluation by Health Canada. CADTH has completed a Horizon Scan report on rapid point-of-care antigen testing for SARS-CoV-2 infection.
Updated on October 5, 2020 | 1:00pm
Covid-19 Rapid Testing Device: ID NOW
On September 30, 2020, Health Canada approved the Abbott ID NOW rapid COVID-19 testing device. ID NOW is approved for use in the laboratory and at the point-of-care for the analysis of samples collected by trained professionals. The device can provide results in less than 15 minutes. The Government of Canada has arranged to procure 7.9 million of the molecular point-of-care tests and up to 3,800 analyzers to provide access to this rapid testing option across the country.
COVID-19 Vaccines: Government of Canada Announcement
On September 25, 2020, the Government of Canada announced a new agreement to secure up to 20 million doses of the COVID-19 vaccine candidate AZD1222, which is being developed by AstraZeneca. This agreement adds to five previous ones that have been put in place to establish a guaranteed supply of potential COVID-19 vaccines for Canadians: the protein subunit vaccine candidate by Sanofi and GlaxoSmithKline (up to 72 million doses); Ad26.COV2.S by Johnson & Johnson (up to 38 million doses); NVX-CoV2373 by Novavax (up to 76 million doses); BNT162 by Pfizer (up to 20 million doses); and mRNA-1273 by Moderna (up to 56 million doses). Clinical trials are still underway to evaluate the efficacy and safety of these vaccines for the prevention of COVID-19, and Health Canada regulatory approval will be required for each vaccine before it is made available to Canadians.
On August 5, 2020, the Government of Canada announced that it has entered into two agreements to secure a future supply of COVID-19 vaccines. An agreement has been made with Pfizer for its BNT162 mRNA-based vaccine candidate and another agreement has been made with Moderna for its mRNA-1273 vaccine candidate. While all potential vaccine candidates will require Health Canada regulatory approval before they are available to Canadians, this move establishes a guaranteed supply of millions of doses of the two previously mentioned vaccines for COVID-19. The government has indicated that other negotiations, investments, and procurement plans are underway.
Azithromycin is a macrolide antibiotic indicated in Canada to treat bacterial infections, such as community acquired pneumonia or skin infections. On September 4, 2020, a multicentre, open-label randomized controlled trial was published comparing azithromycin (oral or intravenous) plus standard of care to standard of care alone (including hydroxychloroquine) for 447 patients hospitalized with COVID-19 in Brazil who required nasal oxygen at 4 L/min, high flow oxygen or mechanical ventilation. There was no statistically significant difference between the treatment groups in terms of the primary outcome of the clinical status at 15 days post randomization. There are ongoing trials investigating azithromycin for the treatment of COVID-19. CADTH will continue to monitor the emerging evidence related to azithromycin in managing COVID-19.
Systemic Corticosteroids
On September 2, 2020, the results of three randomized controlled trials examining the effect of systemic corticosteroids for the treatment of severe COVID-19 were published: the CAPE-COVID trial, the CoDEX trial, and the REMAP-CAP COVID-19 corticosteroid domain trial. In addition, a prospective meta-analysis of seven randomized controlled trials (including the three new trials and the RECOVERY trial) was published. The authors of the meta-analysis concluded that for critically ill patients with COVID-19, the use of systemic corticosteroids was associated with lower 28-day all-cause mortality when compared to placebo or usual care. WHO released a living guidance document that currently provides a strong recommendation for the use of systemic corticosteroids for the treatment of patients with severe and critical COVID-19. At this time, Health Canada recommends that clinicians strongly consider the use of intravenous dexamethasone (or an equivalent glucocorticoid dose) for patients who have COVID-19 and require oxygen or mechanical ventilation. CADTH will continue to monitor the emerging evidence related to corticosteroids in managing COVID-19.
Interferon Beta-1b
Interferon Beta-1b is an immunomodulator indicated in Canada for the treatment of multiple sclerosis. On August 24, 2020, the results of a study on interferon beta-1b for the treatment of COVID-19 were published. The study was a small open-label, single-centre, randomized controlled trial that compared standard of care with standard of care plus interferon beta-1b for the treatment of patients hospitalized with severe COVID-19 in Iran. There were 80 patients randomized, but data are presented for the 66 patients who completed the trial. The primary end point — median time to clinical improvement (two-point improvement on a six-point ordinal scale) — was nine days (interquartile range six days to 10 days) in the interferon group plus standard of care versus 11 days in the standard of care group (interquartile range nine days to 15 days) respectively, P = 0.002, hazard ratio = 2.30; 95% confidence interval: 1.33 to 3.39. CADTH will continue to monitor the emerging evidence related to interferon beta-1b in managing COVID-19.
Chloroquine and Hydroxychloroquine
CADTH has completed a Health Technology Review on chloroquine and hydroxychloroquine and will continue to monitor the emerging evidence related to these drugs for managing COVID-19.
CADTH has completed a Horizon Scan on Favipiravir and will continue to monitor the emerging evidence related to this drug for managing COVID-19.
On July 23, 2020, the results of a study on hydroxychloroquine for the treatment of COVID-19 were published. The study was an open-label, multi-centre randomized controlled trial that compared standard of care, hydroxychloroquine plus standard of care, and hydroxychloroquine with azithromycin plus standard of care for the treatment of patients hospitalized with suspected or confirmed COVID-19 in Brazil (n = 667). There was no statistically significant difference between the groups in terms of the primary outcome of clinical status at day 15; however, there were more adverse effects (including prolonged QT interval and elevated liver enzymes) in the hydroxychloroquine groups. CADTH will continue to monitor the emerging evidence related to hydroxychloroquine or chloroquine in managing COVID-19.
Favipiravir is an oral antiviral drug that has emerged as a potential treatment or prevention option for COVID-19. An international expert panel issued a weak recommendation for not using favipiravir in patients with non-severe or severe COVID-19 because of low-quality evidence. Researchers in Canada plan to conduct a randomized controlled trial evaluating the efficacy of favipiravir compared with placebo for adults living in long-term care homes focused on controlling COVID-19 outbreaks (NCT04448119). Favipiravir is not approved in Canada and is not currently accessible outside of clinical trials. CADTH will continue to monitor emerging evidence related to antiviral agents in COVID-19.
On July 17, 2020, the preliminary results of the RECOVERY study were published comparing dexamethasone plus usual standard of care with usual standard of care alone. The RECOVERY study is a large, ongoing, multi-centre, open-label, randomized controlled trial investigating several treatments for patients hospitalized with COVID-19. CADTH has conducted a critical appraisal of the published results and will continue to monitor the emerging evidence related to systemic corticosteroids in managing COVID-19.
Media inquiries: media@cadth.ca
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It's early days, but we do have two videos posted for our "2018 FND Awareness Day UK!
We were honoured to post both of them, as they are great both in their own ways in how they get across the message about FUNCTIONAL MOVEMENT DISORDER and FND.
That the disorder needs to be now seen and categoriesd up with MS and Parkinsons, this is a real neurological problem and needs to be treated as such.
Instead of us just being left to cope! There needs to be something more, something better set in place to try and keep sufferers pushing themselves. The hospitals could do meet up groups of sufferers in the hospital, how great would that be not to feel so alone in all the agony of painful movements. Plus those that have become disabled, how great to feel a part of the real world! From these meet ups the neurology consultants could learn a lot, watching the interaction showing that sufferers don't want to be left behind. Medical professionals of different types could learn from these groups. Psychologists, psychiatrists, occupational therapists, and of course the neurology consultants. It would be a type of experiment, that would hopefully take sufferers out of depression at least.


1. Tan, H.-Y. (2008, August 28). A party 48 years in the making. Today, p. 31. Retrieved from NewspaperSG.
2. Chua, C. H. (2008, August 18). Mission complete? Li hopes to win medals in singles. The Straits Times, p. 4. Retrieved from NewspaperSG.
3. It's table tennis silver for Singapore. (2008, August 18). The Business Times, p. 26. Retreived from NewspaperSG.
4. Teoh, E. T. (1964, July 19). Will Howe Liang repeat his 1960 feat? The Straits Times, p. 11. Retrieved from NewspaperSG.
5. Joshua, S. (1960, September 15). The 'miracle' in Rome. The Straits Times, p. 13. Retrieved from NewspaperSG.
7. Lee, S. H. (2008, August 17). English telecast of National Day Rally postponed. The Straits Times, p. 1 Retrieved from NewspaperSG.
8. Loh, C. K. (2008, August 18). 'You have not disappointed us'. Today, p. 2. Retrieved from NewspaperSG.
9. Wang, J., Lin, X., & Chia, V. (2008, August 26). Cheers and national honours for winning trio. The Straits Times, p. 6. Retrieved from NewspaperSG.
10. Wang, J., Lin, X., & Chia, V. (2008, August 26). Cheers and national honours for winning trio. The Straits Times, p. 6. Retrieved from NewspaperSG.
11. Tay, C. K. (2004, August 23). No medal but S'pore cheers tearful Jiawei. The Straits Times, p. 1; Chan, T. C. (2000, September 24). Brilliant play from Jing but China's world No. 2 Li plays better. The Straits Times, p. 68. Retrieved from NewspaperSG.
The information in this article is valid as at 13 June 2014 and correct as far as we are able to ascertain from our sources. It is not intended to be an exhaustive or complete history of the subject. Please contact the Library for further reading materials on the topic.


text:
Q: Flip the ACTUAL plot result in MATLAB. I think this might be simple. If we simply plot a vector in MATLAB, it will show it normally, going left to right. That is, the x-axis will have 'time'.
But, I would like to show it going from up to down instead in the plot. How can I do that? In other words, I want the amplitude to be shown on the x-axis, and the time to be shown on the y-axis.
Thanks.

A: Create a vector with the coordinates of your time vector t and flip x and y in your call to plot:
plot(t, 1:length(t));

redpajama_set_name: RedPajamaStackExchange


Archbishop Diarmuid Martin has asked that during the week-end of the Papal visit that Priests and Pilgrims be free to attend. With this in mind there will be Heart, Aughrim. No Morning Mass on Sunday August 26th. in Church of the Sacred.
The 51st Annual Aughrim Sheep Show and Sale will take place in Carnew Mart on Friday September 7th starting at 9am. Entries forms are available from Alan Kinsella 087 2792157 or [email protected]. Presentation Cabaret will be held on the night in O' Toole's, Aughrim at 9pm. Many thanks to all who supported the Commemorative Book. Copies are still available from all committee members for €15.
The numbers: 12, 16, 22 and 23 drawn in the sports club lotto on Monday last August 13th.The jackpot was not won. Match three winners were: Johnnie Dunne, Eilish Byrne and Tasha Hale. The jackpot is €1950.


text:
A few days ago, Eda, Erin and I went to Akihabara to.. well.. be nerds. Actually, Erin wanted some electronic things and the rest of us figured hey, why not tag along. It's been a long time since we've been to Akihabara. Almost the first thing that we noticed, though, was how much it changed.
Of course, some of the stores have changed, and anime's gotten to be more and more popular over there. Or at least, it's a lot more visual than before (the non-porny stuff). Games are still HUGE. But now they're trying to make things more 'family-oriented', it seems. Maid cafes are becoming HUGE, and a place where you can go on a date or with friends, even if you're girls. Not like how a year and a half ago, when Eda and I went to go to one, it was hard to find and out of the way. This time, we (a group of girls) were repeatedly handed fliers from girls in maid costumes advertising various cafes, and even a service that has maids washing your hair! =D
Actually, there's a lot more to Akihabara than just the nerdy gamey porny district that it's world-famous for. But I don't know anything about that except that there's a lot of office buildings, and one of my friends works somewhere in there. ^^ So we took the usual exit from the station, for "Electric Town". Akiharaba is quite unique, at least for Tokyo. It's true that there's a LOT LOT LOT of anime, games, electronics, and porn (pretty much in reverse order, I think). It's a place where you don't want to venture upstairs or downstairs in an innocent-looking electronics building without reading the floor guides first. Otherwise you'll wind up like I did on my first trip there, 2 years ago------ going up one single floor and finding yourself amidst a cornucopia of porn videos. The room's decor of course matched, and *coughs* the clientele........ I was really new to Japan at the time ("fresh off the boat" as we say sometimes...) and didn't have any friends yet; it was quite scary.
Anyways, there's a TINY import food store a little way off the main street, and after I was delighted to find Vanilla Cherry Dr Pepper (OMG sounds so GOOD!!! Even though I don't usually drink soda anymore), we nearly died at all of the fun candies that we found inside..... So here is just a bunch of pictures of weird things we found in Aki....
I am starved to death!!
But at least I'm a cute animal!!
Mr. Blubber tells you that "Cool Man, Blubber ist fun!"! More loving proof that engrish is not limited to asian countries. XD;;
I can't get over it.... who would EAT a candy named "Mr Blubber"?????!?! I mean, wow.... you'd definitely have to not know what it means to even want to go near it (other than to make fun of it and take pictures). Well, at least it's truthful??
I just thought that was cute.... and disturbing, but at least cute!!
I never in my entire life thought that I would see canned snail meat. Not too remarkable, except that it's snails... in a can. x.x.................... (okay, I do like Escargot but..) Hey, it seems that Mr. Snail is a baseball fan!
AHAHAHAAAAAAAA!!!! On par with the "Big German Potato" cup noodle that I found earlier, non? ^o^
Would you like some English? Yummy!!! Oh wait, I see.... it's marmalade, not pureed people as I first thought... Good thing they put that subtitle there!
Van Damme's Coco Blubs.......... I don't need to say anything, do I?
Because Oden is so, so delicious anyways, let's have it in a can!! Yeay? (Okay I lie, it's not horrible.....natto is horrible.... but in a can?????)
And this was in a toy shop.... "Tomorrow's get high today!" Um........ well, the toy hot dog next to it is cute? Why is the marijuana joint holding a banana????
Umm..... they're baaaaaack!! Turns out that big horned thing is from some old campy monster movie (ala Godzilla, but see, Godzilla was classy in comparison ^.^)
Harry Potter is so totally sitting there on the left!!!!!!!!!!!!!! @o@
And the best of all... (nsfw)
Milk Tank Teacher Nene!!!
View 2.
I bet her students really loved her. ^-^ And in case we couldn't tell which part was her face and which was her bust, the makers kindly labeled it for us. Aww, how sweet ♥
By the way, the 16th was my 20year anniversary of arriving to Japan!! Yay!! ^o^ Here's to year number 3, may it bring many great things!! ^O^//", "url": "https://hinoai.livejournal.com/573801.html", "image": { "@type": "ImageObject", "url": "http://namutaku.net/livejournal/eng.jpg" }, "author": { "@type": "Person", "name": "Hi-chan (火ちゃん)", "image": "https://l-userpic.livejournal.com/73641010/693581" }, "publisher": { "@type": "Organization", "name": "Journal hinoai", "logo": { "@type": "ImageObject", "url": "https://hinoai.livejournal.com", "contentUrl": "https://l-userpic.livejournal.com/73641010/693581" } } }
It still can't beat Milk Tank Teacher Nene.. =^o^=
Yes, it is what you think it is ------------------->
By the way, the 16th was my 20year anniversary of arriving to Japan!! Yay!! ^o^ Here's to year number 3, may it bring many great things!! ^O^//
Tags: ☆ i heart japan

redpajama_set_name: RedPajamaCommonCrawl


More than a year and a half after Saudi Arabia unveiled economic reforms under Vision 2030, the Kingdom appears to be making considerable headway in planning and launching key projects that will ultimately give a much-needed boost to its construction sector.
A long list of mega-projects are currently in the pipeline, including an $8 billion expansion of rail services in the country, the development of the $67 billion King Abdullah Economic City, and the $2 billion Jeddah Tower, which is expected to surpass Dubai's Burj Khalifa to become the world's tallest tower when it's completed in 2020.
Business sentiment in the Kingdom's construction market is improving, according to Pinsent Masons' recent Annual GCC Construction Survey, which showed 29 per cent of respondents expecting to see the most opportunity over the next 12 months, compared to just 11 per cent in 2016. According to KPMG's Saudi Arabia 2030: Life after Oil report, the Kingdom's aim to attract foreign and private investment has led to the announcement of large-scale infrastructure projects across the healthcare, transportation, tourism and renewable energy sectors. These announcements have received wide interest and have already had a positive knock-on effect on the country's construction industry.
Last December, Saudi Arabia unveiled its 2018 budget – the largest in its history -which earmarked SAR 54 billion for infrastructure spending. These investments will be used to fund the development of roads, ports, railways, airports, housing, and information technology, along with many other mega projects tied to Saudi Vision 2030. The planned projects support the Saudi government's strategy to leverage its geographical location and position the Kingdom as a logistics hub connecting Asia, Africa and Europe. Work has already begun in recent years to expand the country's airports and develop the Riyadh Metro, the country's first-ever public transport network.
Among the most ambitious aims is the Kingdom's goal to attract 1.5 million leisure tourists by 2020. Considering the fact that Saudi Arabia has mostly relied on religious tourism in the past, there is plenty of room to build new hotels, retail developments and attractions in the foreseeable future. Currently, there are 172 hotel projects in the planning, tender, design and under construction stages according to ProTenders construction intelligence platform, which account for 17% of all active hospitality projects in the GCC. Following the unveiling of Saudi Vision 2030 in 2016, international companies like Rezidor Group and Accor were quick to respond by announcing plans to open dozens of new hotel properties in the Kingdom over the next few years. Other hospitality projects also taking shape are Panorama Jeddah and Movenpick Hotel Waad Al Shamal.
Economic reforms in Saudi Arabia are also expected to present significant opportunities for the private sector to invest in the Kingdom's healthcare industry according to JLL MENA, which identifies the kingdom's ageing population and growing demand for hospitals and other healthcare facilities as key factors that will drive growth within the sector over the next five years. The 2018 budget has allocated SAR 147 billion to expand health services in the country, of which SAR 33 billion will go towards the initiatives linked to Saudi Vision 2030. A total of 36 new hospitals will be built across the Kingdom adding a capacity of 8,950 beds, and two medical cities with a total capacity of 2,350 beds are being constructed. Some of these healthcare facilities already underway are Dr. Sulaiman Al Habib Medical Centre in Jubail, Riyadh Medical City for Rehabilitation & Treatment and Dr. Sulaiman Al Habib Hospital in Al Sahafah District.
Ambitious government targets, a fast-growing population and shift to privatization are creating new growth potential in the expanding construction market. Objectives outlined in Vision 2030 put a major emphasis on public-private partnerships, joint ventures and the privatization of government entities. Such measures will be critical to ensuring the Kingdom achieves its goal of increasing the private sector contribution to the country's gross domestic product (GDP) from 40% to 65% by 2030. By now, local construction companies and foreign ones that want to be part of the Saudi Arabian construction landscape should feel reassured by the government's commitment to the plan's overall success, thus also implying a long-term positive outlook on the Kingdom's construction industry.
ProTenders' Construction Intelligence platform offers the latest market data on the all active and completed construction projects in Saudi Arabia, and other GCC countries. Reach out to us for a demo.


"Praise, support and representation" for said organizations will likewise be removed, Facebook Newsroom reported.
This ban is the latest of the U.S. online company's actions to "prevent and disrupt offline harm." It comes on the heels of similar actions taken by the U.S. social networking service company against other accounts that had been spewing hate through the platform.
In September 2018, the Human Rights Council, in its "Report of the independent international fact-finding mission on Myanmar," stressed Facebook's role in spreading hate speech in the country and called out what it described as its "slow and ineffective" response to inflame discrimination and violence on its platform.
In a country with a long history of intercommunal violence, Facebook – which is equal to the internet in Myanmar – has become a critical battleground for discrimination and marginalization.
They were also known to spread disinformation, or plain wrong information, and tamper with images to instigate hatred, if not violence.
Before 2015, tensions between these armed groups from the northern Shan state had led to the displacement of local villagers. Between January 2017 and September 2018, the United Nations Office for Coordination of Humanitarian Affairs reported that 44,000 villagers from the Shan state had been displaced (see "Myanmar: Civilians displaced by fighting in Kachin/Shan 2017-18"). TNLA is among the four groups included in Facebook's recent ban.
Since August 2018, the company has taken down 425 Facebook Pages, 17 Facebook Groups, 135 Facebook accounts and 15 Instagram account for deliberate misrepresentation and banned Myanmar military officials from the platform.
This damage control necessitates a greater amount of work in a country with more than 100 languages.
SEAPA Journalism Fellows Su Myat Mon and Kyaw Ye Lynn (see "On social media, cleaning up isn't easy") found that news outlets have become the "collateral damage" in Facebook's algorithm and content review against hate speech. While civil society has taken initiatives to fight disinformation and hate speech through media and digital literacy, the workload of moderating 18 million social media users in Myanmar remains problematic.
"It is disappointing that there are so few groups doing this work to counter the spread of fake news online and that most rely on volunteers," Ma Phyu Phyu Thi, research director at Myanmar ICT for Development Organization lamented.