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Op-Ed: 94 percent of readers like this article ( or beware of biased reporting) | Hi, what are you looking for?
Read how limited surveys sometimes lead to biased new reporting.
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How reliable is survey data? Many surveys do meet the necessary robustness criteria, in terms of being composed of a suitable sample size, drawn from representative population, and subject to significance testing against an appropriate probability or confidence interval.
Other surveys are less reliable. The ones that all into this camp are small sample sizes, unrepresentative and with no attempt made to assess the significance of the data. Some also carry very large percentages attempting to support a particular position. Such surveys also lack any presentation of the central tendency ( like the mode, the most common; or the median, the point where 50 percent of the responses are in one direction and 50 percent of the responses are in another direction).
Such surveys are often biased or at least contain leading questions. Or selective bits are extracted from the survey to convey points that are convenient to the public relations company or to they are selective picked by the journalist penning an article ( a form of reporting bias). We can define bias as “ selective revealing or suppression of information ”, and this is sometimes too apparent.
Let’ s take an example, in terms of an employment survey that came across the Digital Journal desk. This concerned the place of work.
The differences of opinion between the work-from-home and the need-to-be-at-work contingent is fairly large. In the middle of this are the hybrid advocates. The question of what is best for the employee can not be easily answered as social and psychological factors come into play, as well as work metrics. Furthermore, there are many jobs where working from home is simply not an option. This creates challenges in workplaces where there are office and non-office jobs, in relation to equitable working practices.
As to what workers make of these issues, surveys tend to have differing results. The survey in question finds that 94 percent of employees a believe they should be able to work from anywhere, so long as they get their work done.
The survey also suggests that a ‘ failure’ to provide that flexibility by the employer makes hiring and retention more difficult.
The 94 percent is a very large figure and it perhaps highlights issues with survey responses to statements that contain ‘ agree/disagree’ scales. The primary concern is that such approaches to data gathering tend to lead to a positive bias.
Moreover, for those who neither agree nor disagree with the statement put in front of them, this can be interpreted in different ways. For example, this may represent either be a “ hidden don’ t know ” ( the respondent has no opinion) or it can mean a neutral opinion ( the respondent is somewhere between agreeing and disagreeing) or it can simply be that the respondent is not inclined to think about the answer.
These types of questions are often ‘ leading’ or ‘ loaded’ in a particular way where there are either insufficient options or the question is hard to disagree with. For example:
Surveys based on structured or semi-structured interviews tend to elicit data that is more meaningful, and they also provide opportunity for the interviewer to probe or to ask follow-up questions, especially where more extreme claims are made. These types of surveys cost money and they may not lead to the ‘ headline grabbing’ soundbite beloved of public relations agencies and, it must be said, a sizable splattering of journalists.
The survey also singles out office workers and it finds favourably towards flexible work arrangements. The survey also infers that people will seek to change jobs in order to secure a job where the commute is rarely required.
The study was also focused on workers in the U.S. and the U.K. ( countries with similar forms of capitalist work relations), made up of around 1,500 full-time office workers. Each of the firms was trading as an international company. Hence, the survey data needs to be looked at as applying to a narrow subpopulation of workers.
Furthermore, the timeframe over which data was gathered is very narrow: the data was collected between December 22, 2021 and January 11, 2022. This time of year is generally associated with workers looking to change jobs, sometimes as a way to battle the ‘ January blues’.
Hence, this particular survey had indications of bias and it would not have been a reliable one to present to readers of Digital Journal.
Dr. Tim Sandle is Digital Journal's Editor-at-Large for science news. Tim specializes in science, technology, environmental, and health journalism. He is additionally a practising microbiologist; and an author. He is also interested in history, politics and current affairs.
Images of Ukrainian troops carrying Javelin missile launchers on their shoulders have flashed around the world.
North Korea conducted a missile test but the launch failed, Seoul said - Copyright AFP Jung Yeon-jeNorth Korea fired a projectile Wednesday but the...
China has moved to free up hospital beds as officials reported thousands of new cases from an Omicron-led coronavirus outbreak.
Ukraine's besieged leader urged the U.S. to reconsider his plea for a no-fly zone, invoking the terror of the September 11 attacks.
COPYRIGHT © 1998 - 2022 DIGITAL JOURNAL INC. Digital Journal is not responsible for the content of external sites. Read more about our external linking. | general |
Ukraine president urges US Congress to reconsider 'no-fly zone ' | Hi, what are you looking for?
Ukraine’ s besieged leader urged the U.S. to reconsider his plea for a no-fly zone, invoking the terror of the September 11 attacks.
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Ukraine’ s besieged leader urged the United States Wednesday to reconsider his plea for a no-fly zone, invoking the terror of the September 11 attacks as he ratcheted up pressure on the White House to move aggressively against the Russian invasion closing in on Kyiv.
More than three weeks into a war that has left hundreds of Ukrainian civilians dead and three million displaced abroad, President Volodymyr Zelensky told the US Congress the conflict was “ a terror that Europe has not seen… for 80 years. ”
“ Remember Pearl Harbor, terrible morning of December 7, 1941, when your sky was black from the planes attacking you, ” he said, recalling the air raid that brought the United States into World War II.
“ Remember September 11, a terrible day in 2001 when evil tried to turn your cities, independent territories, in battlefields, ” he told lawmakers via a video link livestreamed to the nation.
“ Our country experienced the same every day. ”
The third president of post-Soviet Ukraine to address Congress, Zelensky’ s appearance was being touted as the most dramatic by a foreign leader since Winston Churchill spoke before Congress in 1941.
But it was civil rights activist Martin Luther King Jr. that the comedian-turned-wartime leader recalled as he pleaded once again for a no-fly zone to defend Ukraine’ s skies.
“ I have a dream, these words are known to each of you today I can say. I have a need, I need to protect our sky. I need your decision, your help, ” he said.
He addressed President Joe Biden directly, urging him to be “ the leader of peace ” as he showed lawmakers a wrenching video of ruined buildings and injured Ukrainian civilians including children, with the final frame showing the words “ close the sky. ”
US and NATO officials have until now flatly ruled out enforcing a Ukraine no-fly zone, concerned about being dragged into a direct conflict with a nuclear-armed Russia.
– Biden to announce aid –
Zelensky’ s appearance — greeted by a standing ovation in the US Capitol complex — came less than a week after lawmakers green-lit nearly $ 14 billion in humanitarian and military aid for the war-torn nation.
Biden is expected to announce $ 1 billion in new security help to Ukraine later Wednesday — $ 200 million of it already allocated over the weekend and $ 800 million in new funds from the aid package signed into law on Tuesday.
But the renewed call for more help to beef up Ukrainian air defenses beyond Stinger and Javelin missiles is likely to maintain the pressure on Biden to go further.
Many lawmakers have backed Zelensky’ s pleas for US officials to help broker the transfer of Soviet-style weapons to Ukraine, including MiG fighter jets from Poland and S-300 surface-to-air missile systems.
Biden is grappling with concerns that Russia might see the move as an escalation in the conflict, while officials have also raised questions about how useful MiG fighters would be to Kyiv.
With 2,400 staff representing 100 different nationalities, AFP covers the world as a leading global news agency. AFP provides fast, comprehensive and verified coverage of the issues affecting our daily lives.
Images of Ukrainian troops carrying Javelin missile launchers on their shoulders have flashed around the world.
North Korea conducted a missile test but the launch failed, Seoul said - Copyright AFP Jung Yeon-jeNorth Korea fired a projectile Wednesday but the...
China has moved to free up hospital beds as officials reported thousands of new cases from an Omicron-led coronavirus outbreak.
The UN's top court on Wednesday ordered Russia to suspend its invasion of Ukraine.
COPYRIGHT © 1998 - 2022 DIGITAL JOURNAL INC. Digital Journal is not responsible for the content of external sites. Read more about our external linking. | general |
Cash-strapped Sri Lanka seeks IMF bailout | Hi, what are you looking for?
Sri Lanka will seek an International Monetary Fund bailout, President Gotabaya Rajapaksa said on Wednesday.
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Published
Sri Lanka will seek an International Monetary Fund bailout, President Gotabaya Rajapaksa said on Wednesday, to battle record inflation and unprecedented food and fuel shortages as the country runs out of dollars to finance imports.
The South Asia nation is in the throes of its worst economic crisis since independence from Britain in 1948 with long queues forming outside gas stations and rolling daily blackouts imposed across the country.
“ Subsequent to my discussions with the International Monetary Fund, I have decided to work with them, ” Rajapaksa said in an address to the nation a day after meeting with an IMF delegation in Colombo.
A huge crowd stormed the president’ s seaside office over runaway prices with the rising cost of food, medicine and other essential goods causing serious hardship for Sri Lanka’ s 22-million people.
Rajapaksa urged residents to play their part and conserve imported energy to help authorities manage the scarce foreign exchange reserves.
“ By limiting the use of fuel and electricity as much as possible, the citizens too can extend their support to the country at this time, ” Rajapaksa said.
“ I hope that you will understand the responsibility lies with you at this challenging time. ”
He added that IMF help was needed to secure “ a new method ” to repay external debt and sovereign bonds this year with around $ 6.9 billion needed this year for debt servicing.
– Long hard road –
The coronavirus pandemic has hammered the island’ s tourism sector — a key foreign exchange earner — while foreign worker remittances have also declined.
Sri Lanka’ s foreign reserves, which sat at $ 7.5 billion when Rajapaksa took office in November 2019, dropped to $ 2.3 billion at the end of February.
The president said the foreign exchange crisis was the root cause of his country’ s current issues, adding he was aware of the “ difficulties ” faced by people queuing for long hours to buy essential goods.
“ Today, I am determined to make tough decisions to find solutions to the inconveniences that the people are experiencing, ” he said.
But former central bank deputy governor W. A. Wijewardena said he expected Rajapaksa to announce a full-fledged IMF funding program to address the balance of payments crisis.
“ I think his address didn’ t go far enough, ” Wijewardena told AFP. “ The market was looking for a mention of IMF funding that would have underwritten the ( entire) economy. ”
Economist Rehana Thowfeek said the government has a lot of work to do to revive the battered economy.
“ Good to hear reassurances from the president of the IMF route, ” she told AFP. “ The sooner a formal request is made ( to the IMF), the sooner Sri Lanka can begin down the long and hard road ahead. ”
International rating agencies have downgraded Sri Lanka since the pandemic hit, effectively blocking its access to commercial borrowings.
They have also raised doubts about Colombo’ s ability to service its external debt amounting to just over $ 51 billion.
With 2,400 staff representing 100 different nationalities, AFP covers the world as a leading global news agency. AFP provides fast, comprehensive and verified coverage of the issues affecting our daily lives.
The big issue facing Russia’ s military is the future. If the present is godawful, the future could be truly, fatally, disastrous.
Australia has returned 29 religious and cultural artefacts to India, among them several stolen or illegally exported from the country.
A China Eastern passenger jet carrying 132 people crashed onto a mountainside in southern China on Monday causing a large fire.
The EU’ s foreign policy chief Josep Borrell calls Russia’ s attack on port city of Mariupol “ a massive war crime. ”
COPYRIGHT © 1998 - 2022 DIGITAL JOURNAL INC. Digital Journal is not responsible for the content of external sites. Read more about our external linking. | general |
Guinea-Bissau COVID-19 Situation Report, September 2020 | Situation reports are the main reporting tool to monitor UNICEF’ s humanitarian response. They provide an update on the situation and needs of children in a country or region, as well as information on UNICEF’ s response and funding requirements.
The world needs to get water smart. Everyone has a role to play, and we can not afford to wait
`` Particularly shocking '' - Every single minute, 55 children have fled their country. A Ukrainian child has become a refugee almost every single second since the start of the war. | general |
Promoting performance in low clinker cement | For full functionality of this site it is necessary to enable JavaScript. Here are the instructions how to enable JavaScript in your web browser.
Emanuele Gotti and Davide Padovani, Mapei SpA., review a new series of additives designed to enhance the performance of low clinker cements.
In recent years, the cement industry has been forced into a change unlike any before in its long history. Phrases like ‘ green economy’, ‘ CO2 reduction’, ‘ digitalisation’, ‘ zero emissions’, ‘ carbon neutral’, etc., that once applied to other sectors of industry are now core components of any cement producer’ s strategy.
In fact, the production of cement is one of the most significant sources of CO2 emissions, and is estimated to contribute 8% of global emissions. These emissions are produced in part by the decarbonisation of calcareous minerals used for the production of clinker, but also by the large quantities of fuel necessary to reach high temperatures. Overall, it is estimated that for each ton of clinker, approximately 0.84±0.10 t of CO2 is produced and emitted into the atmosphere.
To achieve the goal of carbon neutrality by 2050, the cement industry is implementing a range of measuress. These include, for example:
In addition to this scenario, the Covid pandemic and the ongoing crisis in raw materials/logistics has pointed out the fragility of the traditional cement industry. When considering the effects of this challenge on the main product of the cement industry – the cement itself – the following steps can be distinguished:
Want to read more? To access the full version of this article, and many others, sign up for a free trial of World Cement here: https: //www.worldcement.com/magazine/world-cement/trial/ | business |
Q & A With Aoife Brennan, president and CEO of Synlogic, Inc. | With diversity, equity, and inclusion ( DE & I) a pressing issue at many companies today, Aoife Brennan, president and CEO of Synlogic, describes what her career journey in pharma has looked like as a woman, and what she feels can be done to improve opportunities for other females in pharma. She also talks about how advocacy and commitment can similarly be applied to improve the rare disease space.
Brennan: I trained as an endocrinologist and always saw myself working in an academic teaching hospital. But ultimately, it was curiosity that drove me to accept my first role in pharma with a small, private biotech company working in type 1 diabetes. I realized quickly that the company was backed by great science and great people, and had significant potential to positively impact patient lives. I also really enjoyed the team aspect and the ability to work collaboratively across multiple disciplines.
Over my career, I have been very fortunate to work with great mentors and in organizations where diversity is valued, which is a big reason why I am where I am today. Not everyone is so fortunate. I have had three children while building my career, and quality, reliable childcare was always a struggle. This situation has only deteriorated in the US over the past 10 years, and the COVID-19 pandemic has highlighted and exacerbated this problem even further. I think it is important to look at these barriers not just for the impact they have on individuals but also on how they can affect progress in research and drug development.
On the work front, like many women, I have experienced and witnessed so many episodes of bias. The majority of instances have been unconscious, which I think shows how established these practices have been in our culture. It is true that women are often not given the benefit of the doubt but must prove their competence over and over again. I have seen men who can not deliver at a functional or individual level labeled as “ more strategic ” and given an even bigger job role and thought to myself, “ that would never happen to a woman. ” In addition to unconscious bias, women also still experience blatant acts of misogyny in the workplace, which is stunning in 2022.
Brennan: I think one of the most effective ways to address bias is through representation, changing the image we all have ingrained in our subconscious of what a successful leader, CEO, or chairman looks like. Seeing examples of individuals in prominent leadership positions from all different backgrounds and demographics is so powerful and empowering. We now have multiple great examples of CEOs in biotech who don’ t fit that traditional mold; now people early on in their careers can see themselves in leadership roles, and hopefully we are broadening the image of what a CEO or other leader looks like.
Brennan: The answer here is not hard—make decisions that foster diversity. To do that, you need to understand the benefits. When I think of how to improve workforce diversity, I think of the drug development analog and look across the talent pipeline. In the early phase, we can implement programs that expose high school and college graduates from under-represented demographics to the range of opportunities available in the biotech and pharma industries. For example, at Synlogic, we have had a partnership with the Gloucester Biotechnology Academy for more than six years. This has been a highly successful partnership and we have great team members from this program who continue to build their careers within Synlogic.
At mid-stage, we need to look at the factors that cause us to lose diverse talent and address them systematically. Targeted training in management, HR, planning, strategy, financial, and business acumen can be important. We also need to push for higher levels of objectivity in talent and performance assessment. I read an article recently that found that people from under-represented groups can interpret failure, or a career setback, differently and in a way that damages their sense of belonging. Biotech is full of failure and setbacks, so how do we keep an eye out for the disproportionate impact a career setback can have on certain populations?
In later-stage clinical development, we can help more experienced professionals who have established functional credibility to transition to become enterprise leaders and board members through mentorship, sponsorship, and coaching. This is the stage where having access to the networks of people who have gone before you can really help. The casual conversations among peers are an important learning ground for the skills and insights to be a good leader. In many cases in the pharma industry, ensuring that potential leaders from diverse backgrounds have access to those networks is critical. | tech |
Solo Stove Pi dual-fuel off-grid oven bakes pizzas anywhere | Solo Stove emerged as one of the true all-stars of the COVID-19 pandemic, and it shows no signs of slowing down. The company behind some of the world's favorite smokeless fire pits has now expanded its outdoor kitchen offerings with a pizza oven. Rather than just the fire-top oven accessory some other brands offer, Solo Stove's Pi is a standalone oven that can spit out red-hot pizzas using either wood or gas for fuel. And it can do so anywhere from a small backyard to the deep backcountry.
When the early 2020 days of the pandemic limited out-of-the-house excursions to the backyard, apartment terrace or local park, people naturally looked for products that would enhance the experience. And few things proved more comforting than a fire pit around which folks could socialize at a safe distance, especially a fire pit that sucks in its own smoke so as not to make anyone teary eyed or scratchy throated.
Things didn't slow down when lockdown restrictions began lifting and people started pursuing more distant outdoor adventures and RV trips. Portable by nature, Solo Stove products effortlessly bridged the gap between backyard and great outdoors, and sales continued to roll in. Solo Stove sold US $ 133 million worth of products in 2020 and beat that in the first six months of 2021 with $ 152 million in sales. For the complete 2021 fiscal year, it expects to more than double 2020's total with a forecast of $ 361 million. It will report official FY2021 results on March 29.
Solo Stove has used all that positive momentum to continue growing its ecosystem of fire- and cooking-related products and to increase its larger market footprint. In the second half of last year, it acquired three other outdoor lifestyle brands, Oru Kayak, Chubbies ( apparel) and ISLE ( paddleboards), and launched an IPO.
Now, Solo Stove has stepped back into the outdoor kitchen with the new Pi. Launched on Pi Day 2022 ( Monday, 3/14), the Pi oven stays true to Solo Stove's wood-fired roots. It uses engineering principles developed for Solo's original wood backpacking stoves and fire pits coupled with a `` Demi-Dome '' construction that directs heat down to the full-width cordierite pizza stone. Ceramic insulation keeps the heat inside and ensures that a 12-in pizza cooks in as few as two minutes.
`` Solo Stove customers value experiences and gathering with friends and family, and it’ s hard to think of a better meal to create and share than fresh, homemade pizza, '' said Solo Stove president Clint Mickle in an announcement this week.
Solo Stove estimates that amateur pizza slingers could fire out three to four pizzas in the first hour, taking preheating time into account. It says that the oven can run for roughly three hours on wood fire before the ash pan fills up and requires cleanup.
Should a three-hour runtime seem inadequate or should wood-fire cooking prove otherwise unideal, the Pi can also be outfitted with a removable gas burner for propane cooking. The burner is designed to hook up to a large LPG tank, the likes of which many outdoor chefs have sitting on the deck hooked up to a grill or smoker.
The stainless steel Pi isn't ultra-portable in the way Solo Stove's original backpacking cookers are, but it's designed to travel easily for camping trips, tailgates, beach days and more. It measures just over 15 inches ( 38 cm) tall by 20.5 inches ( 52 cm) in diameter and weighs 30.5 lb ( 13.8 kg). All that's really required to use it are a fuel source and a level surface, ideally something elevated like a table or the grill-style stand Solo has in the works.
The Pi is available to order now, and deliveries will begin in mid May. It retails for $ 425 as a wood-fire-only unit or $ 600 when packaged with the gas burner. Solo Stove also offers several bundles that include accessories like a pizza peel and infrared thermometer.
Source: Solo Stove | science |
Ukraine’ s Zelenskiy pleads with Congress for help fighting Russia: ‘ I call on you to do more’ – live | Joanna Walters
Wed 16 Mar 2022 14.02 GMT First published on Wed 16 Mar 2022 12.16 GMT
From 1.12pm GMT
13:12
“ Right now the destiny of our country is being decided, the destiny of our people, ” Volodymyr Zelenskiy tells US Congress.
The Ukrainian president says the invasion of Ukraine by Russia is about more than Ukraine, it’ s about democracy, freedom, and choosing your own path. It’ s also about “ Europe and the world. ”
He tells the US to hear him “ when we need you right now ”.
He’ s telling America to remember the Pearl Harbor attack by Japan in 1941 that brought the US fully into the second world war, remember the September 11, 2001 terrorist attacks on the US by al-Qaida terrorists.
What is happening to Ukraine is something “ Europe has not seen in 80 years, ” he said.
“ I call on you to do more, ” Zelenskiy said.
He noted that Russia has “ turned the skies into a source of death ” for troops and the public in Ukraine.
Zelenskiy said that Ukraine has now been experiencing the equivalent destruction and horror of a 9/11 or a Pearl Harbor “ every day for three weeks ”.
Almost 3,000 people died on 9/11 when hijacked passenger jets were flown into the twin towers of the World Trade Center in New York, into the Pentagon on the outskirts of Washington, DC, and a final one crashing into a field after passengers overpowered the hijackers en route to the capital.
Updated at 1.44pm GMT
1.55pm GMT 13:55
During his address to the US Congress moments ago, Ukrainian president Volodymyr Zelenskiy unexpectedly paused to play a video prepared by his government.
The video was both poignant and upsetting, and has graphic images of death, including images of the bodies of children and children badly injured while medics try to save their lives in hospital.
Here's the video Zelenskiy played for U.S. lawmakers today ( via @ joshscampbell).pic.twitter.com/UgBhdqX5Ql
It begins with joyful scenes of normal life in Ukraine just a few weeks ago, and juxtaposes images of buildings being bombed, and images of happy people then stills of people weeping in shock and grief, and people desperately fleeing.
The video is going viral online. It was clearly a strategic move by Zelenskiy as the mainstream media carefully calibrates what images it will show on TV, in newspapers and online, in terms of graphic images of death. This video went much further than what the west has seen on its screens so far in this war.
Updated at 2.02pm GMT
1.25pm GMT 13:25
Ukrainian president Volodymyr Zelenskiy says he is almost 45 years old but there is no point in living “ if we can not stop the death ”.
He switches into English to say: “ As the leader of the nation I am addressing President Biden, you are the leader of the nation. I wish you to be the leader of the world. Being the leader of the world means to be the leader of peace. Thank you. ”
Then in Ukrainian he finishes by saying “ Glory to Ukraine. ”
He is waving on screen as he receives a universal standing ovation from the hundreds of representatives and senators gathered on Capitol Hill.
Updated at 1.33pm GMT
1.22pm GMT 13:22
Zelenskiy is asking the west to unite as a union of “ responsible countries that have the consciousness to stop conflict immediately ”.
He invokes the speed with which vaccines against the coronavirus were developed and says if that kind of collective will were to come together to help Ukraine further combat Russia “ we will be able to save thousands of lives in our country ”.
Now, with a soaring violin score, Zelenzkiy shows a heartbreaking video of the bombardment of Ukrainians, including sobbing children trying to evacuate.
It ends with the plea on screen saying “ Close the sky ”.
Updated at 1.35pm GMT
1.15pm GMT 13:15
The Ukrainian president just asked, rhetorically, if it is “ too much to ask ” Nato allies, including the US, to impose a no-fly zone over Ukraine.
He says if it’ s too much, Ukraine also needs vastly more anti-aircraft systems from the west.
He invokes civil rights leader Martin Luther King Jr’ s historic “ I have a dream ” speech delivered in Washington DC, in a plea against systemic racism, in 1963.
“ I have a need, ” he said.
Updated at 1.16pm GMT
1.12pm GMT 13:12
“ Right now the destiny of our country is being decided, the destiny of our people, ” Volodymyr Zelenskiy tells US Congress.
The Ukrainian president says the invasion of Ukraine by Russia is about more than Ukraine, it’ s about democracy, freedom, and choosing your own path. It’ s also about “ Europe and the world. ”
He tells the US to hear him “ when we need you right now ”.
He’ s telling America to remember the Pearl Harbor attack by Japan in 1941 that brought the US fully into the second world war, remember the September 11, 2001 terrorist attacks on the US by al-Qaida terrorists.
What is happening to Ukraine is something “ Europe has not seen in 80 years, ” he said.
“ I call on you to do more, ” Zelenskiy said.
He noted that Russia has “ turned the skies into a source of death ” for troops and the public in Ukraine.
Zelenskiy said that Ukraine has now been experiencing the equivalent destruction and horror of a 9/11 or a Pearl Harbor “ every day for three weeks ”.
Almost 3,000 people died on 9/11 when hijacked passenger jets were flown into the twin towers of the World Trade Center in New York, into the Pentagon on the outskirts of Washington, DC, and a final one crashing into a field after passengers overpowered the hijackers en route to the capital.
Updated at 1.44pm GMT
1.08pm GMT 13:08
Ukrainian president Volodymyr Zelenskiy has appeared on a large screen in the House of Representatives, ready to address a packed chamber full of members of Congress.
House Speaker Nancy Pelosi is now introducing Zelenskiy and praised his “ courageous ” defenses against invading Russian forces.
She also spoke a little Ukrainian.
Now Zelenskiy is beginning, saying he is proud to address Congress from Kyiv under fire from Russia, while the country is “ not giving up ”.
1.03pm GMT 13:03
Richard Luscombe
Volodymyr Zelenskiy delivered a powerful, and oftentimes personal address to Canada’ s parliament on Tuesday, asking prime minister Justin Trudeau how he would feel if it were his country facing the Russian onslaught.
“ Imagine that at 4am each of you start hearing bomb explosions. Severe explosions. Justin, can you imagine hearing it? You, your children hear all these severe explosions: bombing of airport, bombing of Ottawa airport, tens of other cities of your wonderful country. Can you imagine that? ” Zelenskiy said.
“ What words? How can you explain to your children full-scale aggression just happened in your country? You know that this is war to annihilate your state, your country. You know that this is the war to subjugate your people. ”
The themes of Zelenskiy’ s Canadian address, asking for more military and humanitarian aid, and a Nato-enforced no-fly zone over Ukraine, broadly echoed his speech to the UK parliament a week earlier.
During his virtual address to British MPs, Zelenskiy invoked the spirit of Winston Churchill’ s second world war speeches, stating that Ukraine would fight Russia “ until the end, at sea, in the air. We will continue fighting for our land, whatever the cost.
“ We will fight in the forests, in the fields, on the shores, in the streets, ” he said.
12.39pm GMT 12:39
Ukrainian president Volodymyr Zelenskiy is due to address the US Congress, remotely from his bunker in Kyiv, via video link, in what will be one of the most extraordinary scenes on Capitol Hill in recent memory,
The wartime leader has made no secret of the fact that he is increasingly frustrated by the west’ s refusal to use allied air forces to impose a no-fly zone over Ukraine, to try to stop the Russian aerial bombardment on Ukrainian cities.
An idea to send Soviet-style fighter jets from Poland to Ukraine, via US military facilities in Germany, also collapsed earlier this month, as Joe Biden was wary it could be interpreted by Russia as drawing Nato into war.
Zelenskiy is expected to thank the US for strong assistance so far and economic sanctions on Russia, but also to shame and emotionally appeal to lawmakers to get more involved as Russian president Vladimir Putin appears to be out to crush Ukraine.
The Ukrainian president recently gave a remote talk to a group of members of Congress behind closed doors. But his public address today is of the highest profile. He recently gave a powerful address to the British House of Commons, invoking Shakespearean and Churchillian themes, and he addressed Canada’ s parliament yesterday.
Updated at 12.47pm GMT
12.16pm GMT 12:16
Good morning, US politics live blog readers, thanks for tuning in. Ukrainian president Volodymyr Zelenskiy is due to address Congress, remotely from Kyiv, today in a vital address as his country and city are under fire from the Russian invasion. We will have live coverage here. If you would like to follow more of our global, round-the-clock coverage of the war in Ukraine, that live blog can be reached here.
Here’ s what’ s on today’ s US agenda:
Updated at 12.31pm GMT | general |
Fed expected to raise interest rates for first time since 2018, markets rise on Ukraine hopes – business live | Julia Kollewe
Wed 16 Mar 2022 13.16 GMT First published on Wed 16 Mar 2022 07.42 GMT
1.16pm GMT 13:16
Canada’ s annual inflation rate rose to 5.7% in February, the highest since August 1991.
In some better news for the global inflation outlook, wheat prices in Chicago have fallen back along with corn prices, while soybeans rose. Investors have been encouraged by the peace talks between Ukraine and Russia, while rain forecast in the US plains eased concerns over parched crops.
The most-active what contract on the Chicago Board of Trade ended the overnight session 2.5% lower at $ 11.25-1/4 a bushel, after rising more than 5% the previous day.
A Mumbai-based grains dealer at a global trading firm told Reuters:
Ukraine and Russia are holding a good amount of grains stocks. As soon as war ends, this stockpile will be available for shipping.
1.10pm GMT 13:10
US retail sales rose 0.3% in February compared with the month before, a tad less than the 0.4% increase forecast by economists. January’ s growth was revised to 4.9%, according to the US Census Bureau.
Joseph Brusuelas, RSM US chief economist, tweeted:
US Feb retail sales increase 0.3%, ex-autos up 0.2% & control group falls 1.2%. Once inflation accounted for its a bad report. This data was estimated prior to the price shock cascading through the economy following Russian invasion of Ukraine. Big Jan upward revisions to data.
Brian Wesbury, chief economist at First Trust Portfolios, tweeted:
Retail sales increased 0.3% in February…but, US consumers took home fewer goods and services than the month before.Inflation was 0.8% for the month…meaning retail sales actually fell 0.5%.You paid more and got less!
1.03pm GMT 13:03
Here’ s a round-up of today’ s other news.
The drinks maker Fever-Tree and the owner of the Wagamama and Frankie & Benny’ s restaurant chains have warned of dramatic cost increases as the price of commodities and gas and electricity soars and the war in Ukraine adds pressure to their businesses.
Fever-Tree has lowered its profit guidance, blaming a “ dramatic increase ” in commodity prices after Russia’ s invasion of Ukraine. The company, which had forecast adjusted profits of £69m to £72m this year, has downgraded its outlook to between £63m and £69m.
The Federal Reserve is expected to raise interest rates for the first time since 2018 as it struggles with soaring US inflation, the impact of the war in Ukraine, and the continuing coronavirus crisis.
The Fed has a dual mandate – to maximize employment and keep prices under control. The job market and the wider economy have made an impressive recovery from the lows of the pandemic, thanks in part to Fed rate cuts and a massive stimulus program, but prices have increased by 7.9% in the year through February – the highest rate of inflation in 40 years.
The Church of England is pressuring the French energy giant TotalEnergies over its decision not to cut ties with Russia after Vladimir Putin’ s invasion of Ukraine.
The Church’ s pensions board and the manager of its investment fund said they would reconsider their shareholding in the company.
At least 18 private jets or helicopters linked to Russia have been struck from the Isle of Man’ s aircraft register, as the offshore authorities enforce sanctions brought in by the EU and UK.
Three aircraft have been removed in the last week, including a helicopter and private jets believed to be ultimately owned by Roman Abramovich, Oleg Tinkov – an oligarch not subject to direct sanctions – and Dmitry Mazepin.
The UK could eliminate all need for imports of Russian gas this year through a combination of energy efficiency, expanding renewable power generation and a campaign to help people change their behaviour, research has found.
Information campaigns played a strong role in changing people’ s behaviour during the Covid-19 pandemic. Many people are unaware of the savings they could make in energy use through small changes that make no difference to their comfort but can cut bills substantially.
Russian oligarchs will no longer have access to baubles such as the cars, artworks and designer handbags sold by British companies, after the government blocked exports worth hundreds of millions of pounds.
Last year, UK firms in total sold £2.6bn worth of goods to Russia, the biggest slice of which was cars, at around £400m, as wealthy Russians splashed out on prestigious marques such as Aston Martin, Bentley and Rolls-Royce.
12.59pm GMT 12:59
In other insurance news, the boss of the UK insurer Legal & General, Nigel Wilson, was paid £4.5m last year, more than twice the £2.1m he received in 2020.
12.55pm GMT 12:55
Kalyeena Makortoff
The insurance market Lloyd’ s of London has issued the largest ever fine, of more than £1m, in its 336-year history after a member firm mishandled a bullying and harassment case and hosted an inappropriate “ Boys Night Out ” event for staff, our banking correspondent Kalyeena Makortoff reports.
Lloyd’ s announced today that it had issued three charges against Atrium Underwriters in relation to “ serious failures ” by the firm and its senior managers, which came to a head in 2018.
One of the charges related “ a systematic campaign of bullying ” by one male staffer against against a junior employee, that was well known within the firm, but failed to result in any disciplinary measures against the offending worker.
The firm was also charged for “ sanctioning and tolerating ” an annual “ Boys’ Night Out ” where some male employees – including two senior executives – took part in inappropriate initiation games, heavy drinking, and sexual comments about female colleagues that Lloyds said were both “ discriminatory and harassing ” to members of staff. “ Some of this conduct was led, participated in and condoned, by the two senior managers in attendance, ” it said.
John Neal, Lloyd’ s chief executive, said:
We are deeply disappointed by the behaviour highlighted by this case, and I want to be clear that discrimination, harassment and bullying have no place at Lloyd’ s. The robust action we have taken today, including the largest fine ever imposed by the Lloyd’ s Enforcement Board, shows that we will not tolerate poor conduct in our market. Lloyd’ s expects all participants in the market to meet the highest standards of professionalism, and we are continuing to use our powers to intervene when needed.
Christopher Stooke, Atrium’ s chairman, said the company fully accepted the ruling and recognised it must ensure such behaviour “ is never allowed to happen again ”.
With deep regret, it is clear that Atrium failed to live up to its values and serious errors were made when handling these matters. We are sorry for the hurt that this caused and how difficult this been for those affected.
We have moved quickly to address and learn from these past failings and update our policies and procedures to ensure the highest standards.
11.40am GMT 11:40
The UK government released $ 530m of its debts to Iran, ahead of Tehran’ s release of two British-Iranian prisoners, Iran’ s semi-official Fars news agency reported.
The prisoners are Nazanin Zaghari-Ratcliffe, who had been detained by Iran for six years, and Anousheh Ashouri.
BREAKING Two detained British-Iranians Nazanin Zaghari-Ratcliffe and Anousheh Ashouri are heading to a Tehran airport to leave the country, their lawyer Hojjat Kermani told Reuters on Wednesday. # Iran
powerful moment as the BBC first reports that Nazanin Zaghari-Ratcliffe is on her way home after 6 years. a lot of people have been waiting a long time to be able to say that pic.twitter.com/AXZJrOEl1J
10.55am GMT 10:55
European stock markets are pushing higher, with the FTSE 100 index in London up 1% at 7,249 while the Germany, French and Italian exchanges are all about 3% ahead. The pan-European Stoxx 600 index rose 2.6%.
Battered stock markets in China and Hong Kong surged after Chinese vice premier Liu He said Beijing will roll out more measures to boost the Chinese economy, as well as favourable policies for its capital markets.
Investors have also been reassured by promising news on the peace talks between Ukraine and Russia. Ukraine’ s president Volodymyr Zelenskiy said the talks were becoming “ more realistic ” while Russian foreign minister Sergei Lavrov said there was “ some hope for compromise, ” with neutral status for Ukraine – a major Russian demand – now on the table. Talks are due to resume today.
Nearly three weeks into the invasion, Russian troops are stuck outside Kyiv and have suffered heavy losses. They have failed to seize any of Ukraine’ s biggest cities, while heavily bombing and largely destroying some smaller towns and cities.
10.43am GMT 10:43
British and Dutch gas prices have eased following earlier increases, after Russian gas pipeline supplies to Europe fell for a second day.
The British day-ahead price fell 3p to 264p per therm, a 1.1% drop, while the Dutch contract lost nearly 4% to €109.70 per megawatt hour.
Norwegian gas exports to Britain are also down today, because of maintenance work on the Aasta Hansteen field.
10.32am GMT 10:32
The news came as the International Energy Agency warned of a global oil supply shock if there are large-scale disruptions to Russian crude production.
It said in its monthly oil report that 3m barrels per day of Russian oil and products may not make their way to market from April, as western sanctions bite and buyers hold off. It said:
Surging commodity prices and international sanctions levied against Russia following its invasion of Ukraine are expected to appreciably depress global economic growth. As a result, we have revised down our forecast for world oil demand by 1.3m barrels per day from the second to fourth quarter, resulting in 950,00 barrels per day slower growth for 2022 on average. Total demand is now projected at 99.7m barrels per day in 2022, an increase of 2.1m barrels per day from 2021.
The prospect of large-scale disruptions to Russian oil production is threatening to create a global oil supply shock. We estimate that from April, 3m barrels per day of Russian oil output could be shut in as sanctions take hold and buyers shun exports. OPEC+ is, for now, sticking to its agreement to increase supply by modest monthly amounts. Only Saudi Arabia and the UAE hold substantial spare capacity that could immediately help to offset a Russian shortfall.
Russia's invasion of Ukraine raises major questions over oil supply from the world's largest exporter – while the economic impacts of the war lead us to revise down our forecast for global oil demand in 2022 by nearly 1 million barrels a dayRead more ⬇️ https: //t.co/OsyI4jljCc
10.24am GMT 10:24
Boris Johnson is in Abu Dhabi today ahead of talks with United Arab Emirates and Saudi leaders to secure more oil from the Gulf, and ramp up pressure on Russian president Vladimir Putin.
The UK and other countries face spiralling energy costs, as oil prices have surged since Russia’ s invasion of Ukraine nearly three weeks ago. Brent crude is currently trading at $ 101.06 a barrel, up 1.1% on the day.
Johnson will ask Saudi Arabia and UAE to pump more oil, but so far they have snubbed US pleas to increase oil production. The two Gulf states are among few Opec oil exporters that have spare capacity to raise output and potentially offset supply losses from Russia.
The British prime minister said before his meetings, with Abu Dhabi crown prince Mohammed bin Zayed and Saudi crown prince Mohammed bin Salman:
The world must wean itself off Russian hydrocarbons and starve Putin’ s addiction to oil and gas. Saudi Arabia and the United Arab Emirates are key international partners in that effort.
However, UAE remains committed to current production plans set out by the Opec oil cartel and its allies, a source told Reuters.
Johnson will only be the second major Western leader to visit to Saudi Arabia since the killing of journalist and dissident Jamal Khashoggi by Saudi government agents in Istanbul in 2018. His visit comes days after Saudi Arabia executed 81 men, the largest number in a single day, for decades, for alleged offences ranging from militant groups to holding “ deviant beliefs ”.
8.48am GMT 08:48
Nickel trading in London has been halted again on its electronic system, due to a technical issue.
The London Metal Exchange said it halted nickel trading to investigate a potential technical issue with its limit down band and will provide an update as soon as possible.
The LME’ s three-month nickel contract hit its lower trading limit of 5% when it reopened today, after wild swings in prices forced a rare market shutdown last week.
Updated at 9.10am GMT
8.21am GMT 08:21
European stock markets have got off to a good start. The FTSE 100 index in London is 90 points ahead at 7,264, a 1.2% gain. The French and Italian markets rose more than 2%, while Spain’ s Ibex opened 1.7% higher.
While fighting in Ukraine continues, the Ukrainian president Volodymyr Zelenskiy said peace talks between Ukrainian and Russian negotiators looked more realistic, but more time was needed.
The meetings continue, and I am informed, the positions during the negotiations already sound more realist. But time is still needed for the decisions to be in the interests of Ukraine.
The Russian rouble, which has tanked since Russia’ s invasion of Ukraine, edged up 1.6% to 108.31 per dollar.
Russia needs to make $ 117m in bond interest payments today, on two dollar-denominated Eurobonds. Its finance ministry has said it will make the payments in roubles if sanctions prevent it from paying in dollars – a move that markets would regard as a debt default.
The Moscow stock markets remains largely closed by order of the central bank, for the rest of the week. Stocks last traded in Moscow on 25 February. Last week, Russia’ s central bank banned selling of dollars and euros in banking branches, in another step to protect foreign currency liquidity held by local banks, as western sanctions have largely cut the country off from the global financial system.
7.48am GMT 07:48
Nickel trading in London has resumed after it was suspended a week ago, with limits on price moves introduced after wild swings triggered a rate market shutdown.
The London Metal Exchange has introduced a 5% limit on nickel price moves. Some traders said they remained cautious and would wait to see how things worked out, according to Reuters.
The LME suspended nickel trading only for the second time in its 145-year history on 8 March, and extended deadlines for those with obligations to deliver physical metal against its contracts.
The price of nickel, which is used to make stainless steel and is a key component of electric vehicle batteries, had already been rising before Russia’ s invasion of Ukraine sent prices soaring. Russia accounts for 10% of global nickel production and traders have been worried that western sanctions on Moscow could disrupt supplies.
The trading band today will be $ 45,674 to $ 50,482, based on the closing price on 7 March. The LME has said that it will move to a 15% limit similar to the one imposed on other base metals this week for the first time, once the nickel market gets back to normal.
7.42am GMT 07:42
Good morning, and welcome to our rolling coverage of the world economy, the financial markets, the eurozone and business.
European stock markets managed to claw back some losses yesterday, helped by a decline in oil prices below $ 100 a barrel at one stage, which eased fears that an energy price spiral will damage the global economic recovery from Covid-19, while US markets finished strong higher. Ongoing peace talks between Ukrainian and Russian negotiators also helped calm markets.
Today is a big day for the US economy, with the latest retail sales figures for February to be released ahead of the latest interest rate decision for the Federal Reserve Open Market Committee, America’ s central bank.
With US inflation running at 7.9% and likely to head higher, it is all but certain that we will see an interest rate hike of 0.25%, which will push the Fed funds rate range off zero and up to a range of 0.25% to 0.50%. It would be the first rate rise since 2018.
Meanwhile, Russia is due to make two interest payments on bonds today, and there is talk that it could default – however it will have a 30-day grace period to make the coupon payments.
Michael Hewson, chief market analyst at CMC Markets UK said:
European markets look set to open higher this morning, however any rally is likely to find itself pushing against the headwinds of headlines out of Ukraine, as well as the prospect that Russia might default on a bond payment later today. A $ 117m interest payment is due today on a US dollar bond. Russia has said it will pay in roubles which would start the clock ticking on a potential default.
Asian stock markets rallied, with Japan’ s Nikkei closing 1.6% higher and Hong Kong’ s Hang Seng surging 8.8%, while the Shanghai Composite Index added 3.5% on hopes of more economic stimulus in China.
Markets bounced back from the previous day’ s heavy losses, sparked by rising Covid-19 infections in China and fading expectations for an interest rate cut by the People’ s Bank of China. Shanghai issued a working from home directive on Wednesday, while Chinese health authorities reported a slight drop in new Covid cases compared to the previous day.
The Agenda
Updated at 8.13am GMT | general |
How to clean your VR headset | Live Science is supported by its audience. When you purchase through links on our site, we may earn an affiliate commission. Learn more
By Lloyd Coombes published 16 March 22
Learn how to clean your VR headset, whether need to clean your Oculus Quest 2 lenses or any other headset brand.
VR headsets allow us to insert ourselves into incredible experiences and games, but that does come at the cost. Aside from the occasional nausea, there’ s also sweat, hair, and dust that can get trapped in the headset during usage… and that’ s without even factoring in the current pandemic, so you’ ll definitely want to know how to clean your VR headset thoroughly.
Since it's something you 'll be in close contact with your extended periods of time, it's incredibly important to keep the VR headset, and any controllers you’ re using, clean and sanitary. The best VR headsets are expensive, so it's worth looking after them to increase their longevity too. Still, with so many expensive components, some high-quality lenses, and plenty of buttons, it can be tricky to work out how to give your VR setup a clean safely.
Here’ s a breakdown of how to clean a VR headset properly, including tips on what equipment you 'll need, what techniques you should use, and how to clean your lenses safely too.
Disclaimer: This article is for informational purposes only, and is not meant to offer medical advice. If you're concerned that you are ill or contagious, do not invite your friends over to use your VR headset. No, not even to show them Half Life: Alyx.
As with anything that comes into close contact with you, or more specifically your face, VR headsets can build up a variety of germs and bacteria. While you’ re unlikely to hand your shiny Oculus or HTC headset to a random passer-by on the street, it’ s worth taking precautions to prevent transmitting such unpleasantness between members of your household, or just friends that want to have a go at taking on your Beat Saber high score.
With the SARS-CoV-2 virus ( the one that leads to COVID-19) being detectable “ in aerosols for up to three hours ”, according to the National Institutes of Health, you really can never be too careful about what you’ re passing on to other users of your VR headset, which is why knowing how to clean a VR headset is crucial.
Most importantly, if you think you might be infected with coronavirus, don't invite friends over to use your VR headset.
There are a huge number of cleaning products out there, but you’ ll want to be picky and keep an eye out for certain ingredients – or lack thereof – when tackling how to clean a VR headset.
Normally, we’ d advise using alcohol-free products that have antibacterial qualities, particularly wipes. This is because with cleaning gels, the cleaning product can actually get into the cracks of your device’ s outer shell, potentially seeping through to the components inside. The downside is that antibacterial wipes won't destroy coronaviruses like COVID-19, since it's a virus, not a bacteria. if you're worried about COVID ( and who isn't), then you can also consider alcohol-based wipes, but we 'd avoid sprays and gels altogether.
Your lenses will require a more delicate touch, so we’ d suggest a microfiber cloth with a spot of water on. This is because even alcohol-free products can cause some issues with the glass.
Finally, a can of compressed air is your best friend when used correctly, and a nightmare when used too much. Keeping the can a few inches away, fire the air in short bursts to help push dust and dirt out of those hard-to-reach spots, being careful not to push it further into inside the device if you can avoid it.
As you can probably tell, you don’ t want to blast compressed air anywhere near the lenses, either, lest you end up powering sharp pieces of goodness-knows-what into them at speed.
All headsets should be powered down before you start cleaning. If your headset is wired, be sure to unplug it first. If your headset comes with a glasses “ spacer, ” such as the Oculus Quest 2, be sure to remove that and clean it, too.
You’ ll also want to check the manufacturer’ s guidance for cleaning. Some will recommend using more specific methods on certain parts, whereas this guide is more of a general overview. Use the two in conjunction, just to be safe.
Finally, we’ d also recommend washing your hands before you start cleaning and do the same once you’ re done. In fact, this is a good practice to get into when using your headset in any case. Nitrile gloves are also handy when cleaning, but they’ re not a must.
Use your alcohol-free wipes to wipe around the headset, paying close attention to the parts that come into contact with your face during use. That includes all around the “ eye ” portion, with a focus on the nose part, too.
With external cameras on VR headsets, use the microfiber cloth approach to ensure no smearing of the sensors.
We’ d also recommend focusing on the front of the headset, particularly the top and the bottom of the outer shell. This is because it’ s here that you’ ll likely put your hands on the headset to put it on or remove it.
If your headset has a fabric head strap, you can still use your alcohol-free antibacterial wipes on those, but you’ ll need to leave the fabric to dry out completely before using again. We’ d advise against leaving the VR headset to dry outside, since direct sunlight can wreak havoc on the lenses.
Speaking of the lenses, don’ t forget to use the microfiber cloth we recommended earlier. Using this will help minimize friction on the lens, while still picking up anything that may be there. It doesn't matter what brand of headset you're using, the cleaning process is the same whether you're looking to clean Oculus lenses or your Valve Index's lenses.
Use circular motions rather than up and down strokes, starting at the center of the lens and gently working your way outwards. If your lens has dirt or marks that requires a bit of assistance to remove, you can also look at camera lens cleaning fluids, though these can be a little pricey.
It’ s also worth remembering that whether you have a fancy stand for your VR gear, or you’ re just setting it on a table, it’ ll collect germs from those surfaces, too. With that in mind, be sure to give those areas a clean regularly.
If you don’ t use your VR headset all that often, consider a carry case, or even the original box as a place to store it away from bacteria. In fact, this will also help keep it out of direct sunlight, helping ensure the sensors and lenses last longer. | general |
Bolsa de Madrid: Fed, tasa o tarde | Para ser honesto, he estado buscando durante mucho tiempo esta mañana una manera de no insistir demasiado en la decisión de política monetaria que el banco central de los Estados Unidos va a tomar esta noche, y que será la noticia del día. No es que carezca de interés, no me atrevería, sino porque habrá mucho ruido, muchas suposiciones y muchas interpretaciones, como siempre, y como siempre, habrá que esperar a que se asiente la polvareda para tener una buena visión de las consecuencias de la decisión. De todos modos, estaba buscando otras ideas y había empezado a pensar en algunas cuando derramé mi Infusión en mi escritorio. O más bien en mi teclado, por si acaso. Así que, por supuesto, me llevó un tiempo secarlo todo. Desde entonces, me he bañado en una mezcla de tila, verbena, azahar y menta, me dice la caja, y no he podido organizar bien mis pensamientos. Pero de todos modos tengo algunos retazos de información interesantes para compartir con ustedes, porque probablemente no les interesen mis titánicas debacles con las hierbas.
Mientras curioseaba, me di cuenta de que este 16 de marzo es especial. No sólo es el día del diente de león y de San Benito, sino que también es el aniversario del mínimo del IBEX35 durante el crash-flash de marzo de 2020. Ya sabes, cuando se suponía que el coronavirus iba a permitir que el mundo renaciera diferente y mejor. El índice parisino había caído a 5814 puntos durante la sesión de ese día. El 5 de enero de 2022 alcanzó los 8236 puntos, cuando el índice marcó su máximo histórico, y entretanto se duplicó con creces. Desde entonces, las cosas han sido un poco menos suaves, pero los que piensan en términos de vaso medio lleno siempre pueden recordar que el índice de Madrid ha ganado un 60% en dos años, aunque haya cedido 1000 puntos desde principios de enero.
También había encontrado otra cifra interesante. 22%. ¿El 22% de qué? Tengan paciencia, estoy llegando a eso. The Intelligencer, que es una rama de la revista New York, ha publicado un largo artículo titulado `` El capitalismo moderno es más extraño de lo que crees '' y subtitulado `` Ya no funciona como se anuncia ''. Léalo aquí. El periodista recuerda que el 22% de la empresa típica del S & P500 está ahora en manos del trío BlackRock, Vanguard y State Street, los tres principales gestores de activos estadounidenses. Se podría decir que los gestores de activos pasivos, lo cual es probablemente un oxímoron. Porque sus estrategias se basan esencialmente en índices, como probablemente sepa, a través de ETFs. Como escribe el autor del artículo, `` poseen una parte importante de prácticamente todo '', por lo que `` no hay precedentes de esta extraordinaria forma de poder ''. Lo más paradójico es que estos colosos no tienen ningún interés en los resultados de las empresas en las que invierten, ya que se les paga en comisiones y son sus clientes los que están expuestos a los rendimientos de los activos. Siguen teniendo interés en que el sistema funcione, de lo contrario no tendrían clientes, pero esto se consigue principalmente a través de los altos precios de los activos... y, por tanto, de un enfoque muy acomodaticio de la política monetaria. Por lo tanto, es mucho más fácil entender por qué la participación del trío en la empresa típica del S & P500 pasó del 13,5% al 22% entre 2008 y 2022, el periodo dorado del bazooka de liquidez.
La política monetaria es, por tanto, el centro de atención de la sesión de hoy. Se espera que la Fed suba sus tipos de interés en un cuarto de punto esta tarde para empezar a luchar contra la inflación. Esta es la predicción abrumadora del mercado. Hace unas semanas, algunos pensaron que una subida más agresiva de 50 puntos básicos sería un mejor remedio, pero parece que se han desvanecido en el aire. Mientras tanto, la guerra en Ucrania ha agitado el análisis, aunque sólo haya amplificado el problema del aumento de los precios. Así pues, para no provocar el miedo del mercado y un choque económico demasiado fuerte, el banco central debería ceñirse al escenario de referencia. Pero no puedo evitar pensar que enviaría un mensaje mucho más eficaz si esta noche sorprendiera a todos con un doble ajuste monetario. Pero ese tipo de sorpresas ya no se producen en el silencioso mundo de la orientación futura, que consiste en que los bancos centrales del mundo posterior a 2008 exponen sus intenciones con la mayor claridad posible. La decisión se tomará a las 19:00 horas y no a las 20:00, ya que Estados Unidos ha cambiado al horario de verano. Jerome Powell dará la conferencia para presentar la decisión a partir de las 19.30 horas.
Hasta entonces, los informes sobre los combates y las conversaciones en Ucrania seguirán lloviendo como bombas rusas sobre el país. Y hoy es el día en que Moscú debe realizar el pago de los intereses de su deuda. Rusia tiene previsto hacerlo en rublos y no en dólares, lo que constituiría un impago soberano, advirtió Fitch. Sin embargo, a pesar de los titulares sobre la bancarrota del Estado ruso que seguramente aparecerán, el 16 de marzo no es una fecha límite porque hay una tolerancia de varias semanas en este ámbito para compensarlo. Dicho esto, seguirá siendo un acontecimiento con un fuerte impacto simbólico.
Para completar esta mañana, debo añadir que todo vale en los mercados de renta variable chinos. Tras hundirse a principios de semana, han protagonizado un gran rebote ( están en marcha ganancias de más del 20% en Alibaba y Tencent) después de los `` rumores '' difundidos por la agencia oficial Xinhua sobre la voluntad de las autoridades chinas de trabajar por la estabilidad de los mercados de valores y de `` apoyar la cotización de las empresas chinas en el extranjero ''. Si hasta el Partido Comunista Chino empieza a convertir la bolsa en un casino, aún no estamos fuera de peligro.
Los indicadores adelantados europeos y americanos son alcistas esta mañana. El viejo continente tiene que ponerse al día, ya que Wall Street repuntó ayer con fuerza. En Asia, Tokio ganó un 1,6% y Sydney un 1,1%. Esto no es nada comparado con la ganancia del 8% del Hang Seng al final del día.
Lo más destacado de la actualidad económica
La economía estadounidense será el centro de atención hoy con las ventas minoristas de febrero ( 13:30), seguidas por el índice de vivienda NAHB de marzo y los inventarios empresariales de enero ( 15:00), así como los inventarios semanales de petróleo ( 15:30), y finalmente la decisión sobre los tipos de la Fed a las 19:00.
El par euro/dólar cotiza a 1,09667 dólares. La onza de oro vuelve a perder terreno en 1915 dólares. El petróleo sigue cayendo, con el Brent del Mar del Norte a 100,86 dólares y el crudo ligero WTI estadounidense a 96,91 dólares. Los rendimientos de la deuda estadounidense mantienen sus máximos recientes en el 2,14% a 10 años, mientras que la deuda alemana se estabiliza en el 0,36% a la misma duración. El bitcoin ronda los 39.000 dólares. La Bolsa de Metales de Londres ( LME) reanuda esta mañana la negociación del níquel, que se interrumpió la semana pasada tras un episodio de volatilidad insana.
Principales cambios en las recomendaciones
En el mundo
Anuncios importantes ( y otros)
Lecturas | business |
Canada lifting pre-arrival COVID test requirement April 1: Source | The information you requested is not available at this time, please check back again soon.
Vaccinated travellers will no longer require a negative COVID-19 test to come to Canada as of April 1, according to a source in the federal government.
The source, who is not authorized to speak publicly about the upcoming policy change, says an official announcement is expected later this week.
At the end of February, Health Minister Jean-Yves Duclos announced travellers coming to Canada would be able to present a negative rapid-antigen test at the border as an alternative to a more costly and time-consuming molecular test.
At the time, he said he would consider easing COVID-19 travel restrictions further if the epidemiological situation continued to improve, hospitalizations diminished and Canadians continued to get their booster shots.
He also said the government would move away from stiff restrictions now that Canada has more tools to deal with the pandemic.
While Canada's handle on COVID-19 cases has been improving over the last several weeks, the World Health Organization says rates have begun to creep up in Europe and other parts of the world. | general |
Interfor: Notice and Access Notification to Shareholders – Opens application/pdf in new tab | NOTICE AND ACCESS NOTIFICATION TO SHAREHOLDERS
Annual General Meeting of Shareholders to be held on May 11, 2022
You are receiving this notice because Interfor Corporation ( the `` Company '') is using the `` notice and access '' process to deliver the meeting materials for its annual general meeting of shareholders to be held on May 11, 2022 ( the `` AGM ''). Instead of a paper copy of the management information circular for the AGM ( the `` Information Circular ''), shareholders of the Company are receiving this notice and can access the Information Circular online. Accompanying this notice is either a proxy form or voting instruction form, enabling you to vote at the AGM.
AGM Date, Time and Location
DATE:
Wednesday, May 11, 2022
TIME:
12:00 p.m. ( Pacific time)
PLACE:
Rosewood Hotel Georgia
801 West Georgia Street
Vancouver, British Columbia
TELECONFERENCE:
Toll Free number: 1-833-297-9919
You have a right to vote at the AGM if you held Interfor common shares at the close of business on March 15, 2022. Your vote is important and we encourage you to participate in the AGM, either in person or by proxy. Shareholders who attend the AGM in person will be required to adhere to requirements prescribed by public health authorities. Shareholders who attend by teleconference are encouraged to vote in advance by proxy, and attendees will not be able to vote or speak via the teleconference line during the AGM. All shareholders are invited to submit questions to be addressed at the AGM, by sending an email to corporatesecretary @ interfor.comby May 10, 2022.
At the AGM, shareholders will be asked to consider and vote on the following:
PLEASE REVIEW THE INFORMATION CIRCULAR BEFORE VOTING.
INTERFOR 2022
1
Notice and Access Notification
Websites where the Information Circular is Posted
The Information Circular can be accessed online at the Company's website at www.interfor.com/investors/reportson March 15, 2022 and for at least one year after that date. The Information Circular can also be accessed under the Company's profile on SEDAR at www.sedar.com.
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COVID IP Waiver Compromise Bashed By All Sides | A proposed compromise in World Trade Organization talks to waive intellectual property rights for COVID-19 vaccines is being criticized from all sides, with pharmaceutical and business groups saying it threatens medical innovation, and public health groups assailing the plan as not going far enough.The U.S., European Union, South Africa and India, the major players in the talks that have been ongoing for nearly a year and a half, have reached an agreement in principle, U.S. and WTO officials confirmed Tuesday. But final details still need to be worked out, and all 164 members of the WTO would need to sign... | general |
Effects of SARS-CoV-2 on prenatal lung growth assessed by fetal MRI - The Lancet Respiratory Medicine | The COVID-19 pandemic has resulted in a plethora of acute and long-term diseases, with lung health remaining an important focus. Even though reports of fetal viral transmission of SARS-CoV-21Kotlyar AM Grechukhina O Chen A et al.Vertical transmission of coronavirus disease 2019: a systematic review and meta-analysis.Am J Obstet Gynecol. 2021; 224: 35-53Google Scholar and viral placental infection2Patane L Morotti D Giunta MR et al.Vertical transmission of coronavirus disease 2019: severe acute respiratory syndrome coronavirus 2 RNA on the fetal side of the placenta in pregnancies with coronavirus disease 2019-positive mothers and neonates at birth.Am J Obstet Gynecol MFM. 2020; 2100145Google Scholar have raised concerns, implications for longer-term lung health induced by a virus with high affinity to the respiratory epithelium3Bridges JP Vladar EK Huang H Mason RJ Respiratory epithelial cell responses to SARS-CoV-2 in COVID-19.Thorax. 2022; 77: 203-209Google Scholar have not been addressed. Our study was designed to elucidate the effects of SARS-CoV-2 infection on the fetus, especially in light of ongoing discussions about the benefits of vaccination during pregnancy. Additionally, we aimed to inform future studies on pulmonary health in children exposed to SARS-CoV-2 during pregnancy. We used fetal MRI to assess lung volume as a measure of pulmonary growth in the offspring of women with uncomplicated SARS-CoV-2 infection during pregnancy. This study was approved by the local institutional review board ( ethical approval # LMU-207–33).
We analysed the MRI data of 34 pregnant women ( median gestational age 33·5 weeks [ range 24–40 ]; appendix p 3) with only mild symptoms of PCR-proven SARS-CoV-2 infection and no related hospital admissions. Fetal lung volume, normalised to estimated fetal weight, was described as a percentage of the respective 50th percentile reference values ( appendix p 6).4Meyers ML Garcia JR Blough KL Zhang W Cassady CI Mehollin-Ray AR Fetal lung volumes by MRI: normal weekly values from 18 through 38 weeks ' gestation.AJR Am J Roentgenol. 2018; 211: 432-438Google Scholar The effects of gestational age at MRI scan, sex, timepoint ( trimester) of infection ( confirmed by positive PCR), and duration of infection in days ( PCR to MRI) on fetal lung volume were assessed by generalised linear modelling with identity link function for normal distribution. Placental heterogeneity and thrombosis were scored from 0 ( none) to 4 ( severe).
In pregnant women who tested positive for SARS-CoV-2, normalised fetal lung volume was significantly reduced compared with age-adjusted reference values,4Meyers ML Garcia JR Blough KL Zhang W Cassady CI Mehollin-Ray AR Fetal lung volumes by MRI: normal weekly values from 18 through 38 weeks ' gestation.AJR Am J Roentgenol. 2018; 211: 432-438Google Scholar in the absence of structural abnormalities or organ infarction, and was unexplained by differences in somatic growth ( 84% vs 24% of 50th percentile reference; p < 0·0001; figure). The timepoint of infection showed significant effects on fetal lung growth, with reduced lung volumes observed with SARS-CoV-2 infections acquired during the third trimester ( 69% vs 91% of 50th percentile reference in the first or second trimester; p=0·0249; figure). Duration of infection ( p=0·5657), gestational age at MRI scan ( p=0·5704), and sex ( p=0·3721) did not show significant effects. The reduction in normalised lung volume was supported by the masked comparison to a site-specific, SARS-CoV-2-negative control group ( n=15, 95% vs 69% of 50th percentile reference with infection in third trimester; p=0·0050; appendix p 4), as well as a second reader study ( appendix p 4). Compared with pregnant women who tested negative for SARS-CoV-2, pregnant women who tested positive for SARS-CoV-2 showed increased placental heterogeneity ( p=0·0475) and thrombotic changes ( p=0·0230); however, the association between placental changes and normalised lung volume was not significant when taking gestational age at MRI scan into account ( p=0·4508 and p=0·4004, respectively). Neonatal follow-up in 21 ( 62%) of 34 neonates at birth ( gestational age 35–42 weeks) showed adequate birthweight for gestational age and no indication of acute postnatal respiratory distress ( Apgar score 9–10; pulse oximetry 97–100%).FigureEffects of SARS-CoV-2 on fetal lung volume and bodyweightShow full caption ( A) 50th percentile values, 95% confidence level, and 5% confidence level of total fetal lung volume ( mL) over gestational age ( weeks at MRI), and the trend observed in pregnant women with SARS-CoV-2 infection. ( B) 50th percentile reference values of estimated fetal bodyweight ( g) over gestational age ( weeks at MRI) and the trend observed in pregnant women with SARS-CoV-2 infection. ( C) 50th percentile reference values of fetal lung volume-to-bodyweight ratio over gestational age ( weeks at MRI) and the trend observed in pregnant women with SARS-CoV-2 infection. ( D) Fetal lung volume normalised by fetal bodyweight ( expressed as a percentage of 50th percentile reference value) with timepoint of infection in the third trimester vs timepoint of infection in the first or second trimester vs a site-specific, SARS-CoV-2-negative control group.View Large Image Figure ViewerDownload Hi-res image Download ( PPT)
( A) 50th percentile values, 95% confidence level, and 5% confidence level of total fetal lung volume ( mL) over gestational age ( weeks at MRI), and the trend observed in pregnant women with SARS-CoV-2 infection. ( B) 50th percentile reference values of estimated fetal bodyweight ( g) over gestational age ( weeks at MRI) and the trend observed in pregnant women with SARS-CoV-2 infection. ( C) 50th percentile reference values of fetal lung volume-to-bodyweight ratio over gestational age ( weeks at MRI) and the trend observed in pregnant women with SARS-CoV-2 infection. ( D) Fetal lung volume normalised by fetal bodyweight ( expressed as a percentage of 50th percentile reference value) with timepoint of infection in the third trimester vs timepoint of infection in the first or second trimester vs a site-specific, SARS-CoV-2-negative control group.
The effects of SARS-CoV-2 infection during pregnancy on fetal lung development have been largely understudied throughout the COVID-19 pandemic. To our knowledge, this is the first study showing reduced fetal lung volume in otherwise healthy pregnant women with SARS-CoV-2 infection. This reduction was dependent on the timepoint of infection, indicating that the most significant results occurred in the third trimester, thereby overlapping with the saccular stage of lung development dedicated to the expansion of ( future) air spaces.5Schittny JC Development of the lung.Cell Tissue Res. 2017; 367: 427-444Google Scholar Despite equivocal findings on placental transmission,6Mahyuddin AP Kanneganti A Wong JJL et al.Mechanisms and evidence of vertical transmission of infections in pregnancy including SARS-CoV-2s.Prenat Diagn. 2020; 40: 1655-1670Google Scholar predominant viral transmission in the third trimester,1Kotlyar AM Grechukhina O Chen A et al.Vertical transmission of coronavirus disease 2019: a systematic review and meta-analysis.Am J Obstet Gynecol. 2021; 224: 35-53Google Scholar and the significant correlation between positive maternal PCR test and amniotic presence of SARS-CoV-2 near term7Maeda MFY Brizot ML Gibelli M et al.Vertical transmission of SARS-CoV2 during pregnancy: a high-risk cohort.Prenat Diagn. 2021; 41: 998-1008Google Scholar might enhance exposure of the developing lung parenchyma to the virus, facilitated through increased fetal breathing in the third trimester. Specifically, the high affinity of the virus to alveolar epithelial cells3Bridges JP Vladar EK Huang H Mason RJ Respiratory epithelial cell responses to SARS-CoV-2 in COVID-19.Thorax. 2022; 77: 203-209Google Scholar could affect the so-called developmental sprint of these cells. The absence of postnatal respiratory distress in this cohort points to an important, subclinical phenotype related to prenatal exposure to SARS-CoV-2 that should be functionally and structurally addressed in follow-up studies under consideration of exposure to environmental hazards, including infections and toxins. Furthermore, recommendations of SARS-CoV-2 vaccination during pregnancy might be supported by our data.
SS, VK, JR, and AH contributed equally. TK holds stock of Roche and Biontech and has a relative who is employed at Roche. SM is in the advisory board of, and receives research support, honoraria, and travel expenses from AbbVie, AstraZeneca, Clovis, Eisai, GlaxoSmithKline, Medac, Merck, Novartis, Olympus, PharmaMar, Pfizer, Roche, Sensor Kinesis, Teva, and Tesaro. All other authors declare no competing interests. This work was supported by the programme Physician Scientists for Groundbreaking Projects at Helmholtz Zentrum München ( Munich, Germany) and part of the research programme GRK 2338: Targets in Toxicology. The funders of the study had no role in data collection, data analysis, data interpretation, writing of the manuscript, or the decision to submit it for publication.
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Burden of chronic hepatitis B and C infections in 2015 and future trends in Japan: A simulation study - The Lancet Regional Health – Western Pacific | BackgroundDetermining the number of chronic hepatitis B ( HBV) and C virus ( HCV) infections is essential to assess the progress towards the World Health Organization 2030 viral hepatitis elimination goals. Using data from the Japanese National Database ( NDB), we calculated the number of chronic HBV and HCV infections in 2015 and predicted the trend until 2035.MethodsNDB and first-time blood donors data were used to calculate the number of chronic HBV and HCV infections in 2015. A Markov simulation was applied to predict chronic infections until 2035 using transition probabilities calculated from NDB data.FindingsThe total number of chronic HBV and HCV infections in 2015 in Japan was 1,905,187–2,490,873 ( HCV:877,841–1,302,179, HBV:1,027,346–1,188,694), of which 923,661–1,509,347 were undiagnosed or diagnosed but not linked to care ( “ not engaged in care ”), and 981,526 were engaged in care. Chronic HBV and HCV infections are expected to be 923,313–1,304,598 in 2030, and 739,118–1,045,884 in 2035. Compared to 2015, by 2035, the number of persons with HCV not engaged in care will decline by 59·8 – 76·1% and 86·5% for patients in care. For HBV, a 47·3 – 49·3% decrease is expected for persons not engaged in care and a decline of 26·0% for patients engaged in care.InterpretationAlthough the burden of HBV and HCV is expected to decrease by 2035, challenges in controlling hepatitis remain. Improved and innovative screening strategies with linkage to care for HCV cases, and a functional cure for HBV are needed.FundingJapan Ministry of Health, Labour and Welfare.
Determining the number of chronic hepatitis B ( HBV) and C virus ( HCV) infections is essential to assess the progress towards the World Health Organization 2030 viral hepatitis elimination goals. Using data from the Japanese National Database ( NDB), we calculated the number of chronic HBV and HCV infections in 2015 and predicted the trend until 2035.
NDB and first-time blood donors data were used to calculate the number of chronic HBV and HCV infections in 2015. A Markov simulation was applied to predict chronic infections until 2035 using transition probabilities calculated from NDB data.
The total number of chronic HBV and HCV infections in 2015 in Japan was 1,905,187–2,490,873 ( HCV:877,841–1,302,179, HBV:1,027,346–1,188,694), of which 923,661–1,509,347 were undiagnosed or diagnosed but not linked to care ( “ not engaged in care ”), and 981,526 were engaged in care. Chronic HBV and HCV infections are expected to be 923,313–1,304,598 in 2030, and 739,118–1,045,884 in 2035. Compared to 2015, by 2035, the number of persons with HCV not engaged in care will decline by 59·8 – 76·1% and 86·5% for patients in care. For HBV, a 47·3 – 49·3% decrease is expected for persons not engaged in care and a decline of 26·0% for patients engaged in care.
Although the burden of HBV and HCV is expected to decrease by 2035, challenges in controlling hepatitis remain. Improved and innovative screening strategies with linkage to care for HCV cases, and a functional cure for HBV are needed.
Japan Ministry of Health, Labour and Welfare.
Research in context Evidence before this studyIn 2000, the total number of people chronically infected with hepatitis B virus ( HBV) or hepatitis C virus ( HCV) in Japan was 3.01–3.66 million. This number decreased to 2·09 – 2·84 million in 2011. It is essential to assess the change in the number of chronic infections and the progress towards the World Health Organization ( WHO) goal of eliminating viral hepatitis as a public health threat by 2030, compared to 2015. We searched Pubmed for published articles reporting the total number of chronic HBV and HCV infections in Japan in 2015 and/or predicting the trends until 2030. Our search found no research articles reporting such information or indicating the likelihood of Japan to achieve the WHO targets. Added value of this studyThis study provides updated information on the number of people infected with HBV and HCV in Japan in 2015 and forecasts the future number of chronic infections until 2035. We used actual data from the Japan National Database ( NDB) to calculate the number of chronic infections in 2015. The NDB is an exhaustive valuable database for health policymaking and research. The use of this database enables to obtain an accurate picture of the burden of HBV and HCV in Japan. Using the number of chronic infections in 2015 as a baseline and simulation parameters from first-time blood donors and official population statistics, we projected the number of chronic infections in 2030 and 2035. We found that chronic HBV and HCV infections will significantly decrease, but challenges in controlling hepatitis will remain. Implications of all the available evidenceAlthough our findings show that Japan is making progress towards the elimination of viral hepatitis, efforts should be made to identify undiagnosed HCV cases and link them to care with highly effective direct-acting antivirals. Improved screening and innovative approaches for identifying persons infected with chronic HCV are recommended. For HBV, it is essential to develop new therapies that allow for a complete cure.
In 2000, the total number of people chronically infected with hepatitis B virus ( HBV) or hepatitis C virus ( HCV) in Japan was 3.01–3.66 million. This number decreased to 2·09 – 2·84 million in 2011. It is essential to assess the change in the number of chronic infections and the progress towards the World Health Organization ( WHO) goal of eliminating viral hepatitis as a public health threat by 2030, compared to 2015. We searched Pubmed for published articles reporting the total number of chronic HBV and HCV infections in Japan in 2015 and/or predicting the trends until 2030. Our search found no research articles reporting such information or indicating the likelihood of Japan to achieve the WHO targets.
This study provides updated information on the number of people infected with HBV and HCV in Japan in 2015 and forecasts the future number of chronic infections until 2035. We used actual data from the Japan National Database ( NDB) to calculate the number of chronic infections in 2015. The NDB is an exhaustive valuable database for health policymaking and research. The use of this database enables to obtain an accurate picture of the burden of HBV and HCV in Japan. Using the number of chronic infections in 2015 as a baseline and simulation parameters from first-time blood donors and official population statistics, we projected the number of chronic infections in 2030 and 2035. We found that chronic HBV and HCV infections will significantly decrease, but challenges in controlling hepatitis will remain.
Although our findings show that Japan is making progress towards the elimination of viral hepatitis, efforts should be made to identify undiagnosed HCV cases and link them to care with highly effective direct-acting antivirals. Improved screening and innovative approaches for identifying persons infected with chronic HCV are recommended. For HBV, it is essential to develop new therapies that allow for a complete cure.
The World Health Organization ( WHO) estimates that 296 million people were living with chronic hepatitis B infection, and 58 million people had chronic hepatitis C infection worldwide, representing 4·4% of the world population in 2019.1World Health OrganizationGlobal progress report on HIV, viral hepatitis and sexually transmitted infections, 2021.Accountability for the Global Health Sector Strategies 2016–2021: Actions for Impact. WHO, Geneva2021Google Scholar As a result, in 2016, the WHO set a target for eliminating viral hepatitis by 2030.2World Health OrganizationGlobal Health Sector Strategy on Viral Hepatitis 2016–2021. Towards Ending Viral Hepatitis. WHO, Geneva2016Google Scholar The implementation of the hepatitis B vaccine at birth and the approval of potent nucleos ( t) ide analogues ( NA) and direct-acting antivirals ( DAA) have made the elimination of hepatitis B virus ( HBV) and hepatitis C virus ( HCV) infections possible. However, despite these advances, viral hepatitis remains a major cause of death globally, raising concern about the satisfactory prevention and management of cirrhosis and hepatocellular carcinoma ( HCC).
Japan has a long history of combatting viral hepatitis. The routes of HBV infection used to be horizontal transmission and mother-to-child transmission ( MTCT). After World War II, improved hygiene and the introduction of disposable devices in medical institutions are estimated to have reduced the rate of horizontal transmission of various blood sources, including HBV and HCV.3Moriya T. Koyama T. Tanaka J. Mishiro S. Yoshizawa H. Epidemiology of hepatitis C virus in japan.Intervirology. 1999; 42: 153-158Google Scholar As a result of the decline in cases of HBV infection due to horizontal transmission, it is estimated that in the population born in the early 1980s, the majority of cases of chronic HBV infection may be due to MTCT.4Sato T. Do S.H. Asao T. et al.Estimating numbers of persons with persistent hepatitis B virus infection transmitted vertically and horizontally in the birth cohort during 1950-1985 in Japan.Hepatol Res. 2014; 44: E181-E188Google Scholar
Therefore, since 1986, a nationwide project for the prevention of MTCT of HBV has been implemented, with the screening of all pregnant women for hepatitis B surface antigen ( HBsAg) and the administration of hepatitis B vaccine and Hepatitis B immune globulin ( HBIG) to children born to women testing positive for HBsAg.5Tanaka J. Akita T. Ko K. Miura Y. Satake M. Countermeasures against viral hepatitis B and C in Japan: an epidemiological point of view.Hepatol Res. 2019; 49: 990-1002Google Scholar,6Shiraki K. Perinatal transmission of hepatitis B virus and its prevention.J Gastroenterol Hepatol. 2000; 15 ( Suppl): E11-E15Google Scholar Using data from the prefectures where the strategy was piloted, the prevention rate was found to be over 90%, and has been maintained until now.7Koyama T. Matsuda I. Sato S. Yoshizawa H. Prevention of perinatal hepatitis B virus transmission by combined passive-active immunoprophylaxis in Iwate, Japan ( 1981–1992) and epidemiological evidence for its efficacy.Hepatol Res. 2003; 26: 287-292Google Scholar,8Noto H. Terao T. Ryou S. et al.Combined passive and active immunoprophylaxis for preventing perinatal transmission of the hepatitis B virus carrier state in Shizuoka, Japan during 1980–1994.J Gastroenterol Hepatol. 2003; 18: 943-949Google Scholar The rate of chronic infections in infants was 0·26% in 1985, before the implementation of the project, and decreased to 0·024% in 1995.6Shiraki K. Perinatal transmission of hepatitis B virus and its prevention.J Gastroenterol Hepatol. 2000; 15 ( Suppl): E11-E15Google Scholar The project is running under the universal health insurance system for about 36 years, and more than 98% for children born to HBsAg-positive pregnant women benefited from the prophylaxis.
To further control HBV and HCV infections, viral hepatitis screening has been introduced in the resident health checkups since 2002.9Oza N. Isoda H. Ono T. Kanto T. Current activities and future directions of comprehensive hepatitis control measures in Japan: The supportive role of the hepatitis information center in building a solid foundation.Hepatol Res. 2017; 47: 487-496Google Scholar Since 2008, all patients who submit a subsidy application to the government can receive treatment by NAs, DAAs, or interferon ( IFN) at a reduced cost.9Oza N. Isoda H. Ono T. Kanto T. Current activities and future directions of comprehensive hepatitis control measures in Japan: The supportive role of the hepatitis information center in building a solid foundation.Hepatol Res. 2017; 47: 487-496Google Scholar Also, Japan has implemented a national action plan to combat viral hepatitis in 2010, which provides comprehensive support for patients in testing, treatment, and care. Under this plan, individuals with chronic HBV or HCV are referred to dedicated health facilities for viral hepatitis management. Furthermore, in 2016, universal vaccination against hepatitis B has been expanded to cover all infants.10Ujiie M. Sasaki K. Yoshikawa N. Enami T. Shobayashi T. Introduction of a hepatitis B vaccine into the national routine immunisation programme of Japan.Lancet Infect Dis. 2016; 16: 1325Google Scholar Thus, Japan is expected to become one of the leading countries to achieve viral hepatitis elimination within the next decade.
To assess the effectiveness of countermeasures and the progress towards controlling HBV and HCV, it is essential to keep track of the number of infections.1World Health OrganizationGlobal progress report on HIV, viral hepatitis and sexually transmitted infections, 2021.Accountability for the Global Health Sector Strategies 2016–2021: Actions for Impact. WHO, Geneva2021Google Scholar In 2000, the total number of people chronically infected with HBV or HCV in Japan was 3·01–3·66 million.11Tanaka J. Akita T. Ohisa M. et al.Trends in the total numbers of HBV and HCV carriers in Japan from 2000 to 2011.J Viral Hepat. 2018; 25: 363-372Google Scholar In 2011, this number was estimated to be 2·09–2·84 million, representing a decrease of approximately one million from the 2000 estimates.11Tanaka J. Akita T. Ohisa M. et al.Trends in the total numbers of HBV and HCV carriers in Japan from 2000 to 2011.J Viral Hepat. 2018; 25: 363-372Google Scholar
This study aimed to calculate the number of chronic HBV and HCV infections in 2015 in Japan, using the National Database of Health Insurance Claims and Specific Health Checkups of Japan ( NDB) and countrywide statistics. Subsequently, based on the number of chronic infections in 2015, a Markov model was applied to predict the infection burden until 2035.
Japan has a national health coverage system where all residents must join the health insurance system.12Matsuda S. Fujimori K. The claim database in Japan.Asian Pac J Dis Manag. 2014; 6: 55-59Google Scholar Insurance claims and health checkups from all hospitals and clinics in Japan are recorded into the NDB, which contains demographics, diagnosis, medical practice, and drug prescription information of all patients.12Matsuda S. Fujimori K. The claim database in Japan.Asian Pac J Dis Manag. 2014; 6: 55-59Google Scholar The NDB is one of the most comprehensive national databases globally and is used for health policymaking and research. Diagnostic data in the NDB are classified using the International Classification of Diseases version 10 ( ICD-10) codes. We requested and obtained data with ICD-10 codes related to liver diseases between April 2012 and March 2016: B15 – B19 ( viral hepatitis), C15 – C26 ( malignant neoplasms of digestive organs), D10 – D36 ( benign neoplasms), D37 – D48 ( neoplasm of unknown or unspecified nature), K70 – K77 ( liver disease), K80 – K87 ( disorders of the gallbladder, biliary tract, and pancreas), and K90 – K93 ( other diseases of the digestive system). A total of 25.9 billion medical records, 3.5 billion Diagnostic Procedure Combination ( DPC) records, and 9.8 billion prescription records with at least one disease name related to liver diseases ( total of 25,212,790 patients) were provided by the Japan Ministry of Health Labor and Welfare ( MHLW) to our research group, the Epidemiological Research Group on the Burden of Viral Hepatitis and Measures for its Elimination ( VH-Epi group).
In Japan, blood donation is completely voluntary and supplied by the Japanese Red Cross Society ( JRC). Blood donation is authorised for people aged 16–69 years old. Before donating blood, all donors are asked to complete a questionnaire about their lifestyle, personal and family health history and are examined by a licensed physician. Individuals with a high risk of transfusion-transmitted diseases, including hepatitis B and C, are temporarily or permanently deferred from donating. First-time donors are not compensated and donate blood voluntarily to benefit those in need. Therefore, first-time blood donors are considered a healthy population, and hepatitis virus prevalence in this group is close to the actual prevalence in the general population without disease.13Tanaka J. Koyama T. Mizui M. et al.Total numbers of undiagnosed carriers of hepatitis C and B viruses in japan estimated by age- and area-specific prevalence on the national scale.Intervirology. 2011; 54: 185-195Google Scholar Sex and age-specific prevalence of HBV and HCV infections among 358,291 first-time blood donors in 2015 were provided to the VH-Epi group by the JRC.
Since 2008, the Japanese government subsidises treatment for people diagnosed with chronic hepatitis B and C infections.9Oza N. Isoda H. Ono T. Kanto T. Current activities and future directions of comprehensive hepatitis control measures in Japan: The supportive role of the hepatitis information center in building a solid foundation.Hepatol Res. 2017; 47: 487-496Google Scholar The subsidy policy started with IFN and was later extended to NAs and DAAs. To benefit from this subsidy, patients have to submit an application to the local government. Data on government-subsidized medical expenses for hepatitis treatment are publicly available.14Office for Promotion of Hepatitis Measures Cancer, and Disease Control Division, Health Service Bureau. Subsidies for medical expenses for hepatitis treatment. Ministry of Health, Labour and Welfare ( In Japanese). https: //www.mhlw.go.jp/bunya/kenkou/kekkaku-kansenshou09/080328 josei.html. Accessed 17 April 2021.Google Scholar In this study, we used data from 2008 to 2015.
Vital statistics in Japan are health statistics issued annually by the MHLW. This publicly available database contains national data on the burden of diseases in Japan.15Ministry of Health Labour and WelfareVital Statistics in Japan. Ministry of Health Labour and Welfare, 2021http: //www.stat.go.jp/english/data/kokusei/index.htmlGoogle Scholar
Population census has been conducted every five years since 1920 and covers the whole territory of Japan. We used the census data of 2000, 2005, 2010 and 2015.16Statistics Bureau of Japan. Population Census. Statistics Bureau of Japan https: //www.mhlw.go.jp/english/database/db-hw/vs01.html. Accessed 17 April 2021.Google Scholar
Persons living with chronic HBV or HCV infections were classified into six groups: undiagnosed, diagnosed but not linked to care, patients engaged in care, newly infected, cured, and deaths.
The number of undiagnosed individuals was based on HBsAg and HCV antibody ( Anti-HCV) positivity rates by sex and age group in the first-time blood donors in 2015 and the population census in 2015.17Tanaka J. Report on The Awareness And Course of Action After Hepatitis Virus Testing. Japan: MHLW scientific research subsidy, Research Project for Emergency Measures to Conquer Hepatitis, Japan: Ministry of Health, Labour and Welfare of Japan, 2018: 2018Google Scholar The sex- and age-specific prevalence of HBV and HCV in first-time blood donors is presented in Supplementary Table S1. We assumed that 70% of individuals testing positive for anti-HCV were chronically infected with HCV, and all individuals testing positive for HBsAg were infected with HBV.18Japan Society of HepatologyWhite Paper on Liver Cancer. Japan Society of Hepatology, 2015Google Scholar In Japan, the rate of chronic infections peaks among baby boomers for HBV and among the elderly for HCV. Therefore, the number of undiagnosed cases in those under 16 years was calculated using HBV and HCV prevalence in the 16–19 age group. Similarly, the number of undiagnosed people over 65 years was approximated by HBV and HCV positivity rates in the 50-65 age group.
Individuals diagnosed but not linked to care were defined as people who tested positive for chronic hepatitis infection and were not linked to care. We first calculated the total number of chronic infections in 2015 by adding new chronic infections since 2000 to the previously published number of chronic infections in 2000 and subtracting individuals who achieved SVR and those who died. Then, the number of people diagnosed but not linked to care in 2015 was calculated by subtracting undiagnosed and patients engaged in care from the total number of chronic infections in 2015.
From the crude NDB data on liver disease, we extracted all records related to HBV or HCV infection and the type of treatment received. We implemented a methodology to ensure the reliability of the extracted data. The number of patients engaged in care, whether on treatment or clinical monitoring only, was characterized by sex, age group, liver disease status, and type of treatment. The complete procedure for calculating the number of patients engaged in care is presented in Supplementary Figure S1.
The number of new HCV infections was calculated based on the sex- and age-specific incidence rate among blood donors in 1994–200419Tanaka J. Mizui M. Nagakami H. et al.Incidence rates of hepatitis B and C virus infections among blood donors in Hiroshima, Japan, during 10 years from 1994 to 2004.Intervirology. 2008; 51: 33-41Google Scholar and 2008–201320Uchida S. Satake M. Kurisu A. et al.Incidence rates of hepatitis C virus infection among blood donors in Japan: a nationwide retrospective cohort study.Transfusion. 2018; 58: 2880-2885Google Scholar cohorts. We applied this rate to the sex- and age-specific population in Japan in 2000, 2005, and 2010 to identify the number of new HBV and HCV infections between 2000 and 2015. New chronic HCV infections were assumed to account for 70% of all new infections.18Japan Society of HepatologyWhite Paper on Liver Cancer. Japan Society of Hepatology, 2015Google Scholar
For HBV, new chronic infections are considered rare due to the successful implementation of countermeasures for preventing MTCT since 1986, and the low rate of progression to chronicity if infected in adulthood.5Tanaka J. Akita T. Ko K. Miura Y. Satake M. Countermeasures against viral hepatitis B and C in Japan: an epidemiological point of view.Hepatol Res. 2019; 49: 990-1002Google Scholar, 6Shiraki K. Perinatal transmission of hepatitis B virus and its prevention.J Gastroenterol Hepatol. 2000; 15 ( Suppl): E11-E15Google Scholar, 7Koyama T. Matsuda I. Sato S. Yoshizawa H. Prevention of perinatal hepatitis B virus transmission by combined passive-active immunoprophylaxis in Iwate, Japan ( 1981–1992) and epidemiological evidence for its efficacy.Hepatol Res. 2003; 26: 287-292Google Scholar, 8Noto H. Terao T. Ryou S. et al.Combined passive and active immunoprophylaxis for preventing perinatal transmission of the hepatitis B virus carrier state in Shizuoka, Japan during 1980–1994.J Gastroenterol Hepatol. 2003; 18: 943-949Google Scholar It is estimated that there were only 47 ( 95% CI: 0–145) cases of HBV MTCT in 2016 nationwide.21Sugiyama A. Yamashita M. Ko K. et al.Epidemiological assessment of interventions to eliminate mother-to-child transmission of hepatitis B virus in Japan.Gastrohep. 2021; 3: 72-79Google Scholar However, even though MTCT is rare, there is still a possibility of infection in utero,22Terrault N.A. Levy M.T. Cheung K.W. Jourdain G. Viral hepatitis and pregnancy.Nat Rev Gastroenterol Hepatol. 2021; 18: 117-130Google Scholar or in the family ( horizontal infection), including father-to-child infection in early childhood.23Hirota T. Ohno N. Yano K. Father-to-child transmission of hepatitis B virus.Kanzo. 1987; 28: 427-432Google Scholar Therefore, based on the number of mother-to-child infections ( 0–145 cases per year), and adding a few cases of horizontal infections, the number of new chronic HBV infections was assumed to be 0–200 cases per year.
Cure was defined as the achievement of sustained virologic response ( SVR) in HCV-treated patients. The number of individuals cured was calculated based on the government-subsidized medical claims for hepatitis treatment and the SVR rate following HCV treatment. SVR rates were assumed to be 60% after interferon ( IFN) therapy, 70% after triple therapy ( Pegylated IFN-Ribavirin-protease inhibitor), and 95% after DAA therapy.18Japan Society of HepatologyWhite Paper on Liver Cancer. Japan Society of Hepatology, 2015Google Scholar For HBV, we did not consider a virologic cure ( viral eradication).
The same methodology as previously reported was used for the cumulative number of deaths.11Tanaka J. Akita T. Ohisa M. et al.Trends in the total numbers of HBV and HCV carriers in Japan from 2000 to 2011.J Viral Hepat. 2018; 25: 363-372Google Scholar Briefly, the probabilities of death in 2000, 2005 and 2010 were calculated by dividing the number of deaths from all causes by the population for each year. Then, these probabilities were successively applied to the number of persons with chronic infections each year to obtain the number of deaths per year.15Ministry of Health Labour and WelfareVital Statistics in Japan. Ministry of Health Labour and Welfare, 2021http: //www.stat.go.jp/english/data/kokusei/index.htmlGoogle Scholar However, it is reported that persons with chronic HBV or HCV infections have an excess all-cause mortality rate compared to the general population.24Amin J. Law M.G. Bartlett M. Kaldor J.M. Dore G.J. Causes of death after diagnosis of hepatitis B or hepatitis C infection: a large community-based linkage study.Lancet. 2006; 368: 938-945Google Scholar, 25Ireland G. Mandal S. Hickman M. Ramsay M. Harris R. Simmons R. Mortality rates among individuals diagnosed with hepatitis C virus ( HCV); an observational cohort study, England, 2008 to 2016.Euro Surveill. 2019; 24: 1800695Google Scholar, 26Yamasaki K. Tomohiro M. Nagao Y. et al.Effects and outcomes of interferon treatment in Japanese hepatitis C patients.BMC Gastroenterol. 2012; 12: 139Google Scholar On the other hand, it is also reported that all-cause mortality rate of individuals with inactive chronic HBV infection is similar to that of the general population.27Kumada T. Toyoda H. Yasuda S. Ito T. Tanaka J. Mortality of inactive hepatitis B virus carriers in Japan is similar to that of the general population.Hepatol Res. 2022; 52: 81-92Google Scholar Considering these parameters, we adjusted the number of deaths, assuming a relative risk of all-cause death of 1·0 – 1·4 for HBV, and 1·0 – 2·0 for HCV.
Based on the burden of HBV and HCV infections in 2015, we performed a mathematical simulation using the Markov model to predict the trend in the number of chronic infections until 2035.
To construct the liver disease transition pathway for both HBV and HCV, we stratified the individuals chronically infected with HBV or HCV into two groups: ( i) undiagnosed and diagnosed but not linked to care, that is “ not engaged in care ” and ( ii) patients engaged in care. We further subdivided the patients engaged in care between those on treatment and those receiving clinical monitoring only. Four liver disease states were considered. The definitions of these liver disease states for HBV were the same as previously reported28Tanaka J. Kumada H. Ikeda K. et al.Natural histories of hepatitis C virus infection in men and women simulated by the Markov model.J Med Virol. 2003; 70: 378-386Google Scholar: •Asymptomatic carriers ( AC): patients with ALT less than 35 IU/L for one year and no abnormal findings on medical imaging, •Chronic Hepatitis ( CH): patients with ALT greater than 35 IU/L for one year and no abnormal findings on medical imaging, •Liver Cirrhosis ( LC): clinical diagnosis according to the guidelines of the Japan Society of Hepatology ( medical imaging), •Hepatocellular Carcinoma ( HCC). clinical diagnosis according to the Japan Society of Hepatology ( medical imaging).
For HCV, we used the following categories, as described by Yamasaki et al.29Yamasaki K. Tanaka J. Kurisu A. et al.Natural course of persistent hepatitis B virus infection in hepatitis B e antigen-positive and hepatitis B e antigen-negative cohorts in Japan based on the Markov model.J Med Virol. 2018; 90: 1800-1813Google Scholar: •AC: patients with an alanine aminotransferase ALT level below 35 IU/L and HBV viral load less than 4·0 log IU/mL, but without liver cirrhosis, •CH: patients with an ALT level greater or equal to 35 IU/L and HBV viral load greater or equal to 4·0 log IU/mL, but without liver cirrhosis, •LC: patients with one or more of the following criteria: i) aspartate aminotransferase ( AST) -to-platelet ratio index greater or equal to 1·4 ( AST level 80 IU/L or less), ii) fib-4 index value greater or equal to 3·6, iii) platelet count less than or equal to 130,000, or iv) esophageal or gastric varices at endoscopy, •HCC: diagnosis based on liver biopsy or laparoscopy.
In the case of patients on treatment, we further divided liver cirrhosis patients into two groups by their status of compensated ( C-LC) or decompensated ( D-LC) ( Figure 1). Thus, the transition pathway took into account within-group and between-group transitions.aHCV ( Figure 1A): The disease pathway starts with uninfected subjects who become newly infected and move to the liver disease transition cycle among undiagnosed and diagnosed but not linked to care. Some may be screened for HCV and linked to care, thus moving to the transition cycle among patients on clinical monitoring. A number of patients may receive treatment by antivirals ( DAA or IFN) or hepatoprotective drugs ( such as ursodeoxycholic acid or glycyrrhizic acid), and some may achieve SVR. Despite the treatment, a few subjects who achieve SVR may still develop HCC. Death was the final stage and was separated into liver-related deaths and other causes of death. Each liver disease states were mutually exclusive and collectively exhaustive.bHBV ( Figure 1B): The design of the HBV transition pathway followed the same structure as for HCV. However, no virologic cure was assumed.Figure 1Transition pathway of liver disease. This figure shows the transition pathway of liver disease for HCV ( Figure 1A) and HBV ( Figure 1B) based on the natural history of liver disease [ Asymptomatic carriers ( AC), Chronic Hepatitis ( CH), Liver Cirrhosis ( LC), and Hepatocellular Carcinoma ( HCC) ] and classified into groups of undiagnosed and diagnosed but not linked to care, and patients engaged in care ( on treatment or clinical monitoring only). Dashed lines represent changes between the groups, and straight lines notify the progression in liver disease. Death is the absorbing state and is classified into liver-related deaths and deaths from other causes.View Large Image Figure ViewerDownload Hi-res image Download ( PPT)
The 1-year probabilities of change in liver state for undiagnosed and diagnosed but not linked to care were the same as in our previously published research ( Supplementary Table S2 for HCV and Table S3 for HBV). These probabilities were based on long-term observation of individuals diagnosed with HBV or HCV after blood donation or community health screening.
The transition probabilities for patients either on treatment or clinically monitored were calculated based on the NDB data and stratified by age, sex, and treatment type ( Supplementary Tables S4 and S5).
The parameters used for our simulation are shown in Table 1.Table 1Baseline data for the 2015–2035 prediction of HBV and HCV trends.HCVHBVNoteChronic infections in 2015Undiagnosed and diagnosed but not linked to care AC94,678–258,485721,461–791,010Based on the number of undiagnosed in 201111Tanaka J. Akita T. Ohisa M. et al.Trends in the total numbers of HBV and HCV carriers in Japan from 2000 to 2011.J Viral Hepat. 2018; 25: 363-372Google Scholar CH138,992–379,46737,87–41,523Based on the number of undiagnosed in 201111Tanaka J. Akita T. Ohisa M. et al.Trends in the total numbers of HBV and HCV carriers in Japan from 2000 to 2011.J Viral Hepat. 2018; 25: 363-372Google Scholar LC2,890–7,89110,344–11,341Based on the number of undiagnosed in 201111Tanaka J. Akita T. Ohisa M. et al.Trends in the total numbers of HBV and HCV carriers in Japan from 2000 to 2011.J Viral Hepat. 2018; 25: 363-372Google Scholar HCC1,153–3,14712,305–13,491Based on the number of undiagnosed in 201111Tanaka J. Akita T. Ohisa M. et al.Trends in the total numbers of HBV and HCV carriers in Japan from 2000 to 2011.J Viral Hepat. 2018; 25: 363-372Google ScholarPatients clinically monitored AC048,568Calculated based on NDB data CH163,080102,061Calculated based on NDB data C-LC8,0053,625Calculated based on NDB data DC-LC3,8671,377Calculated based on NDB data HCC6,2512,738Calculated based on NDB dataPatients on treatment CH315,343129,033Calculated based on NDB data C-LC40,89410,970Calculated based on NDB data DC-LC35,4297,713Calculated based on NDB data HCC80,32022,252Calculated based on NDB dataNew chronic infections70% of new infections reported by Uchida et al.20Uchida S. Satake M. Kurisu A. et al.Incidence rates of hepatitis C virus infection among blood donors in Japan: a nationwide retrospective cohort study.Transfusion. 2018; 58: 2880-2885Google Scholar0-200Based on the incidence rates among blood donorsTransition probabilities Undiagnosed and diagnosed but not linked to careSupplementary Table S2Supplementary Table S3Transition probabilities among the general population Patients clinically monitored onlySupplementary Table S4Supplementary Table S5Calculated based on NDB data Patients on treatmentSupplementary Table S4Supplementary Table S5Calculated based on NDB dataScreening Number of people screened1,000,0001,000,000Based on Regional Public Health and Health Promotion Services reports31Kaishima T. Fujii T. Matsuoka T. et al.Study of the issues of receiving hepatitis screening and the rate of consulting hospitals-the rate of recognized receiving hepatitis screening and that of the unrecognized.Kanzo. 2016; 57: 634-648Google Scholar,32Ministry of Health Labour and Welfare. Regional public health and health promotion services reports ( 2008–2015). Ministry of Health Labour and Welfare. https: //www.mhlw.go.jp/english/database/db-hss/rrphshps.html. Accessed 17 April 2021Google Scholar Positivity rate1% 1% Based on Regional Public Health and Health Promotion Services reports31Kaishima T. Fujii T. Matsuoka T. et al.Study of the issues of receiving hepatitis screening and the rate of consulting hospitals-the rate of recognized receiving hepatitis screening and that of the unrecognized.Kanzo. 2016; 57: 634-648Google Scholar,32Ministry of Health Labour and Welfare. Regional public health and health promotion services reports ( 2008–2015). Ministry of Health Labour and Welfare. https: //www.mhlw.go.jp/english/database/db-hss/rrphshps.html. Accessed 17 April 2021Google Scholar Linkage to care rate ( for positive individuals) 50% 50% Based on Regional Public Health and Health Promotion Services reports31Kaishima T. Fujii T. Matsuoka T. et al.Study of the issues of receiving hepatitis screening and the rate of consulting hospitals-the rate of recognized receiving hepatitis screening and that of the unrecognized.Kanzo. 2016; 57: 634-648Google Scholar,32Ministry of Health Labour and Welfare. Regional public health and health promotion services reports ( 2008–2015). Ministry of Health Labour and Welfare. https: //www.mhlw.go.jp/english/database/db-hss/rrphshps.html. Accessed 17 April 2021Google ScholarDistribution of liver disease state at diagnosisSame as Tanaka et al.6Shiraki K. Perinatal transmission of hepatitis B virus and its prevention.J Gastroenterol Hepatol. 2000; 15 ( Suppl): E11-E15Google ScholarSame as Tanaka et al.4Sato T. Do S.H. Asao T. et al.Estimating numbers of persons with persistent hepatitis B virus infection transmitted vertically and horizontally in the birth cohort during 1950-1985 in Japan.Hepatol Res. 2014; 44: E181-E188Google ScholarBased on the distribution of liver disease state among undiagnosed individualsProportion of D-LC among LC patients46·4% 41·3% Calculated based on NDB dataProportion of C-LC among LC patients53·6% 58·7% Calculated based on NDB dataDistribution of the type of treatmentCalculatedCalculatedCalculated based on NDB dataHCC incidence after SVR CH0·3% NAJSH guidelines on HCV33Japan Society of HepatologyJapan society of hepatology guidelines for the management of hepatitis C virus infection: 2019 update.Hepatol Res. 2020; 50: 791-816Google Scholar C-LC1·1% NAJSH guidelines on HCV33Japan Society of HepatologyJapan society of hepatology guidelines for the management of hepatitis C virus infection: 2019 update.Hepatol Res. 2020; 50: 791-816Google Scholar D-LC0% NAJSH guidelines on HCV33Japan Society of HepatologyJapan society of hepatology guidelines for the management of hepatitis C virus infection: 2019 update.Hepatol Res. 2020; 50: 791-816Google Scholar HCC0% NAJSH guidelines on HCV33Japan Society of HepatologyJapan society of hepatology guidelines for the management of hepatitis C virus infection: 2019 update.Hepatol Res. 2020; 50: 791-816Google ScholarDeaths Liver-related deathsD-LC15·1% 22·2% MHLW report34Hirao T. Report on the Study on Medical Economic Evaluation of Various Measures for Viral Liver Diseases. Ministry of Health Labour and Welfare, 2013: 2013Google ScholarHCC15·4% 12·6% MHLW report34Hirao T. Report on the Study on Medical Economic Evaluation of Various Measures for Viral Liver Diseases. Ministry of Health Labour and Welfare, 2013: 2013Google Scholar Other causes of deathVital statistics in Japan15Ministry of Health Labour and WelfareVital Statistics in Japan. Ministry of Health Labour and Welfare, 2021http: //www.stat.go.jp/english/data/kokusei/index.htmlGoogle ScholarAC, asymptomatic carrier; CH, chronic hepatitis; LC, liver cirrhosis; HCC, hepatocellular carcinoma; C-LC, compensated liver cirrhosis; D-LC, decompensated liver cirrhosis; HCV, hepatitis C virus; HBV, hepatitis B virus; NDB, national database; SVR, sustained virologic rate; JSH, Japanese Society of Hepatology; NA, not applicable Open table in a new tab
We set the following parameters for the simulation of HCV: •Newly diagnosed: 5,000 per year, based on the number of people screened by the health promotion project ( 1,000,000), the rate of chronic HCV infection ( 1%),5Tanaka J. Akita T. Ko K. Miura Y. Satake M. Countermeasures against viral hepatitis B and C in Japan: an epidemiological point of view.Hepatol Res. 2019; 49: 990-1002Google Scholar,9Oza N. Isoda H. Ono T. Kanto T. Current activities and future directions of comprehensive hepatitis control measures in Japan: The supportive role of the hepatitis information center in building a solid foundation.Hepatol Res. 2017; 47: 487-496Google Scholar,30Ministry of Health Labour and WelfareImplementation of Viral Hepatitis Screening by the Health Promotion Project. Ministry of Health Labour and Welfare, 2008Google Scholar according to the MHLW guidelines on HCV screening procedure using a combination of quantitative anti-HCV test and nucleic acid amplification tests, and the rate of medical consultation for those screened positive ( 50%).31Kaishima T. Fujii T. Matsuoka T. et al.Study of the issues of receiving hepatitis screening and the rate of consulting hospitals-the rate of recognized receiving hepatitis screening and that of the unrecognized.Kanzo. 2016; 57: 634-648Google Scholar,32Ministry of Health Labour and Welfare. Regional public health and health promotion services reports ( 2008–2015). Ministry of Health Labour and Welfare. https: //www.mhlw.go.jp/english/database/db-hss/rrphshps.html. Accessed 17 April 2021Google Scholar•Initial HCV treatment: based on the NDB data, the initial treatment distribution among patients with chronic hepatitis was 67·6% for hepatoprotective drugs, 30·7% for DAAs, and 1·7% for IFN. Among patients with compensated liver cirrhosis, the calculated proportions were 71·6% for hepatoprotective drugs, 27·6% for DAAs, and 0·9% for IFN. Until 2019, the Japanese Society of Hepatology guidelines for the management of hepatitis C was not recommending antiviral treatment for patients with decompensated liver cirrhosis or HCC.33Japan Society of HepatologyJapan society of hepatology guidelines for the management of hepatitis C virus infection: 2019 update.Hepatol Res. 2020; 50: 791-816Google Scholar Therefore, we assumed that these patients were treated by hepatoprotective drugs only.•SVR rates for each treatment type: 0% for hepatoprotective drugs, 95% for DAAs, and 50% for IFN.18Japan Society of HepatologyWhite Paper on Liver Cancer. Japan Society of Hepatology, 2015Google Scholar•Mortality due to decompensated liver cirrhosis and liver cancer: 15·1% and 15·4%, respectively.34Hirao T. Report on the Study on Medical Economic Evaluation of Various Measures for Viral Liver Diseases. Ministry of Health Labour and Welfare, 2013: 2013Google Scholar•Proportions of compensated and decompensated liver cirrhosis: 53·4% and 46·6%, respectively, based on the NDB data.•1-year incidence rate of liver cancer after SVR: 0·3% for SVR after chronic hepatitis and 1·1% for SVR after compensated cirrhosis.33Japan Society of HepatologyJapan society of hepatology guidelines for the management of hepatitis C virus infection: 2019 update.Hepatol Res. 2020; 50: 791-816Google Scholar
The following parameters were applied to the simulation of HBV: •Newly diagnosed: 5,000 per year, using the same assumptions as for HCV, based on the number of people screened by the health promotion project and the test positivity and consultation rates.•Initial HBV treatment: based on the NDB data, 77,714 patients were treated with NAs and 70,002 with hepatoprotective or anticancer drugs in 2015. The distribution of medication type at HBV treatment initiation was assumed to be 50% for NAs and hepatoprotective or anticancer drugs.•Annual NA initiation rate among individuals previously treated with hepatoprotective or anticancer drugs: 12·49% for chronic hepatitis, 13·24% for compensated liver cirrhosis, and 6·32% for decompensated liver cirrhosis, based on the NDB data.•Mortality due to decompensated liver cirrhosis and liver cancer: 22·2% and 12·6%, respectively.34Hirao T. Report on the Study on Medical Economic Evaluation of Various Measures for Viral Liver Diseases. Ministry of Health Labour and Welfare, 2013: 2013Google Scholar•Initial proportions of compensated and decompensated liver cirrhosis: 58·7% and 41·3%, respectively, based on the NDB data.
We performed a one-way sensitivity analysis to assess the influence of parameters on the predicted number of HBV and HCV chronic infections in 2030 and 2035. For HCV: incidence rate among blood donors ( 1 to 5 times the base value), newly diagnosed cases ( 2,500–7,500 per year), receiving rate of DAA among CH patients ( 15-90%), receiving rate of DAA among C-LC patients ( 15–90%). For HBV, the sensitivity analysis considered a number of newly diagnosed cases varying between 2,500 and 7,500.
Data from the NDB were obtained in accordance with the Guidelines for the Provision of Information on Receipt and Specified Health Examination established by the MHLW ( approval number MHLW-H-0722-13).
Before donating blood, all donors signed an informed consent form stating that their laboratory test results could be used for research purposes. The ethics committee for epidemiological research of Hiroshima University waived the requirement for further consent ( approval number E-1082).
All study procedures were performed following the applicable regulations and guidelines.
This work was supported by MHLW Policy Research for Hepatitis Measures Program Grant Number JPMH19HC1001. The funders had no role in the study design, data collection, analysis, or manuscript preparation.
The calculated number of chronic HBV and HCV infections in 2015 was 1,905,187–2,490,873, of which 877,841–1,302,179 were HCV and 1,027,346–1,188,694 were HBV. Based on the calculation, HCV accounted for 46.1–52·3% of the total number of chronic infections, and HBV accounted for 47·7–53·9%. The number of undiagnosed, diagnosed but not linked to care and patients engaged in care in 2015, as well as new infections, patients cured, and deaths between 2000 and 2015, are shown in Table 2 and Figure 2.Table 2Distribution of chronic HBV and HCV infections in 2015.HCVHBVHBV and HCVIn 2015 Total877,841– 1,302,1791,027,346–1,188,6941,905,187– 2,490,873 Undiagnosed224,652452,107–455,099676,759–679,751 Diagnosed, not linked to care0–424,338246,902–405,258246,902–829,596 Patients engaged in care653,189328,337981,526On treatment471,986169,968641,954Direct-Acting Antivirals108,073-108,073Interferon5,602 * For HBV, few patients are treated with interferon and were combined in the others category group, with hepatoprotective and anticancer drugs.5,602Nucleos ( t) ide analogues-77,71477,714Others358,31192,254450,565Clinical monitoring only181,203158,369339,5722000-2015New infections in 2000-201534,66738,856–41,84873,523–76,515New chronic infections in 2000-201524,2670–2,992†24,267–27,259New chronic infections in 20151670–200†167–367Viral eradication in 2000–2015 ‡340,000–500,0000340,000–500,000Deaths in 2000–2015328,319–1,154,084207,433–394,870535,752–1,548,954HBV, Hepatitis B virus; HCV, Hepatitis C virus, †Regarding the number of new cases of chronic HBV infections, cases of HBV mother-to-child transmission are rare due to the effect of Hepatitis B vaccine measures at birth and infancy. In addition, HBV infection in adulthood is rarely chronic except for genotype A.‡Viral eradication for HCV is defined as the achievement of SVR after treatment. To date, no treatment allows the eradication of HBV. For HBV, few patients are treated with interferon and were combined in the others category group, with hepatoprotective and anticancer drugs. Open table in a new tab Figure 2Breakdown of the number of chronic HBV and HCV infections in Japan in 2000 and 2015. Distribution of the number of persons living with chronic HBV and HCV infections in 2015 compared to previously published results in 2000.11Tanaka J. Akita T. Ohisa M. et al.Trends in the total numbers of HBV and HCV carriers in Japan from 2000 to 2011.J Viral Hepat. 2018; 25: 363-372Google Scholar In 2015, chronic HBV and HCV infections were classified into two groups ( undiagnosed and patients engaged in care), whereas in 2015 they were classified into six groups: undiagnosed, diagnosed but not linked to care, patients engaged in care ( on clinical monitoring only or treatment), newly infected, cured, and deaths.View Large Image Figure ViewerDownload Hi-res image Download ( PPT)
†Regarding the number of new cases of chronic HBV infections, cases of HBV mother-to-child transmission are rare due to the effect of Hepatitis B vaccine measures at birth and infancy. In addition, HBV infection in adulthood is rarely chronic except for genotype A.
‡Viral eradication for HCV is defined as the achievement of SVR after treatment. To date, no treatment allows the eradication of HBV.
Table 3 and Figure 3 show the predicted number of chronic HBV and HCV infections until 2035. A decrease in chronic infections is expected over the next 20 years for HBV and HCV, with a faster decrease for HCV.Table 3Trend in the number of HBV and HCV undiagnosed, diagnosed but not linked to care, and patients engaged in care from 2015 to 2035.YearHCVHBVHBV and HCVUndiagnosed and diagnosed but not linked to carePatients engaged in careTotalUndiagnosed and diagnosed but not linked to carePatients engaged in careTotalUndiagnosed and diagnosed but not linked to carePatients engaged in careTotal2015224,652–648,990653,189877,841–1,302,179699,009–860,357328,3371,027,346–1,188,694923,661–1,509,347981,5261,905,187–2,490,8732020182,690–564,730270,566–270,567453,256–835,297616,921–764,794310,462927,383–1,075,256799,611–1,329,524581,028–581,0291,380,639–1,910,5532025136,417–461,629167,803–167,808304,220–629,437531,181–664,123291,647822,828–955,769667,598–1,125,752459,450–459,4551,127,048–1,585,206203092,308–357,068119,457–119,472211,765–476,540442,430–558,939269,119711,548–828,058534,738–916,007388,576–388,591923,313–1,304,598203553,698–261,15388,128–88,158141,826–349,311354,289–453,569243,003597,292–696,573407,987–714,722331,131–331,162739,118–1,045,884HBV, Hepatitis B virus; HCV, Hepatitis C virus. Open table in a new tab Figure 3Trends in chronic HBV and HCV infections between 2015 and 2035 by simulation. Simulation of the dynamics of chronic HCV ( Figure 3A) and HBV ( Figure 3B) infections between 2015 and 2035, based on Markov model. Left and middle graphs show the lower estimates of the cumulative number of chronic infections ( left) and the distribution of chronic infections by liver disease state ( middle). Right graphs represent the trend in the number of undiagnosed, diagnosed but not linked to care, and patients engaged in care until 2035, compared to previously published results in 2000 and 2011.11Tanaka J. Akita T. Ohisa M. et al.Trends in the total numbers of HBV and HCV carriers in Japan from 2000 to 2011.J Viral Hepat. 2018; 25: 363-372Google ScholarView Large Image Figure ViewerDownload Hi-res image Download ( PPT)
HBV, Hepatitis B virus; HCV, Hepatitis C virus.
In 2030, the number of individuals undiagnosed for HCV and those diagnosed but not linked to care ( living with chronic HCV and not engaged in care) is expected to be 92,308 – 357,068. As for HCV patients engaged in care, the number of persons is expected to be 119,457–119,472. Concerning HBV, 442,430 – 558,939 people are expected to be not engaged in care, and 269,119 patients will be engaged in care.
Compared to 2015, it is expected that by 2035, the number of persons not engaged in care for HCV will decline by 59·8 – 76·1% and 86·5% for patients engaged in care. For HBV, a 47·3–49·3% decrease in persons not engaged in care is expected, along with a 26·0% decrease for patients engaged in care. The breakdown of the trend in the number of patients engaged in care by type of treatment is shown in Supplementary Table S6. The age- and sex-specific total number of chronic infections from 2015 to 2035 is presented in Supplementary Table S7.
The number of chronic HBV and HCV infections is expected to decrease yearly ( Figure 3). For HCV, although chronic hepatitis will account for most HCV-liver disease states, the number of chronic hepatitis is expected to significantly decrease over the next 20 years ( Figure 3A). As for HBV, the number of asymptomatic carriers will still account for more than half of the total number of chronic infections in 2035 ( Figure 3B).
The results of the sensitivity analyses are presented in Supplementary Figure S2. The factors most influencing the number of chronic HCV infections in 2030 and 2035 are the rates of new infection and diagnosis. Indeed, if HCV incidence rate is five times higher than our base value, 520,101 persons will be chronically infected in 2030 and 401,030 in 2035. On the other hand, if the number of newly diagnosed cases is 7,500 per year, chronic infections will be 456,027 in 2030 and 323,971 in 2035. For HBV, if the number of newly diagnosed cases is 7,500 per year, the projected number of chronic infections in 2030 and 2035 will be 828,031 and 694,450, respectively.
Using actual data from the NDB, we calculated the number of chronic HBV and HCV infections in 2015 and predicted the trend until 2035.
Our previous report on the total number of chronic HCV infections was 1,694,954–2,194,954 in 2000 and 983,879–1,583,879 in 2011.11Tanaka J. Akita T. Ohisa M. et al.Trends in the total numbers of HBV and HCV carriers in Japan from 2000 to 2011.J Viral Hepat. 2018; 25: 363-372Google Scholar In the present study, the total number of chronic HCV infections decreased to 877,841–1,302,179. For HBV, the total number decreased from 1,317,752–1,467,752 in 2000, to 1,118,627–1,268,627 in 2011 1,027,346–1,188,694 in 2015. Our prediction model showed that this decreasing trend will continue until 2035, and the number of persons chronically infected will gradually decrease due to the increase in the number of deaths on the one hand and as a result of the countermeasures on the other hand.
In Japan, hepatitis virus testing under the geriatric health program for the entire population started in 2002, and hepatitis virus testing is still being conducted under the health promotion program. Nationwide surveys on hepatitis virus testing rates were conducted in 2011 and 2017.5Tanaka J. Akita T. Ko K. Miura Y. Satake M. Countermeasures against viral hepatitis B and C in Japan: an epidemiological point of view.Hepatol Res. 2019; 49: 990-1002Google Scholar Over these six years, HCV testing rate increased from 47·9% to 61·6%, and that of HBV increased from 57·7% to 71·0%.17Tanaka J. Report on The Awareness And Course of Action After Hepatitis Virus Testing. Japan: MHLW scientific research subsidy, Research Project for Emergency Measures to Conquer Hepatitis, Japan: Ministry of Health, Labour and Welfare of Japan, 2018: 2018Google Scholar However, in 2015, the number of persons not engaged in care, either undiagnosed or diagnosed but not linked to care, was 224,652–648,990 for HCV and 699,009–860,357 for HBV. Our simulation results show that more than 50,000 HCV- and 300,000 HBV-infected individuals will still be undiagnosed or diagnosed but not linked to care in 2035. Finding undiagnosed cases is one of the main challenges for eliminating HCV. Innovative screening strategies are needed for early diagnosis and linkage to care. Artificial intelligence ( AI) applied to population health records has been suggested to assist in identifying undiagnosed persons, especially those with a high-risk of infection, and reduce false-positive results.35Doyle O.M. Leavitt N. Rigg J.A. Finding undiagnosed patients with hepatitis C infection: an application of artificial intelligence to patient claims data.Sci Rep. 2020; 10: 10521Google Scholar As the NDB is a comprehensive database, the use of AI can help identify undiagnosed cases and link them to care.
The number of HCV patients engaged in care is expected to continue to decrease more substantially compared to HBV. This decreasing trend could be partly explained by countermeasures against HCV and advances in treatment, including widespread screening, improved access to anti-HCV treatment, and high rates of SVR achievement after treatment. Indeed, the management of HCV infection has improved substantially with the introduction of interferon-free Direct Acting Antivirals ( DAA) in 2014, which have few side effects and an SVR rate of 95% or higher regardless of the genotype.33Japan Society of HepatologyJapan society of hepatology guidelines for the management of hepatitis C virus infection: 2019 update.Hepatol Res. 2020; 50: 791-816Google Scholar,36Zoratti M.J. Siddiqua A. Morassut R.E. et al.Pangenotypic direct acting antivirals for the treatment of chronic hepatitis C virus infection: a systematic literature review and meta-analysis.eClinicalMedicine. 2020; 18100237Google Scholar Treatment algorithms are now very simple for patients. However, although the Japanese government subsidises treatment for people who request it, some infected persons are still not linked to care and remain untreated despite being diagnosed.5Tanaka J. Akita T. Ko K. Miura Y. Satake M. Countermeasures against viral hepatitis B and C in Japan: an epidemiological point of view.Hepatol Res. 2019; 49: 990-1002Google Scholar The main reasons for not attending hospitals for care include time constraints and unawareness of the progression of the infection to liver cancer.31Kaishima T. Fujii T. Matsuoka T. et al.Study of the issues of receiving hepatitis screening and the rate of consulting hospitals-the rate of recognized receiving hepatitis screening and that of the unrecognized.Kanzo. 2016; 57: 634-648Google Scholar This highlights the importance of awareness-raising and re-engagement in care for the control of HCV infection.
Although an overall decrease in the total number of chronic HBV infections is anticipated, the number of HBV patients engaged in care is expected to decrease slowly. To date, no HBV treatment achieves a virologic cure, and the anticipated decrease in the number of patients is thought to be caused by mortality. Therefore, new therapies against HBV that allow a complete cure with viral eradication and decreased risk of progression to HCC are needed. Promising drugs under investigation, alone or in combination, offer hope of finding a cure for HBV patients.37Revill P.A. Chisari F.V. Block J.M. et al.A global scientific strategy to cure hepatitis B.Lancet Gastroenterol Hepatol. 2019; 4: 545-558Google Scholar
In 2016, WHO advocated for eliminating hepatitis infections, expressed as a 95% reduction in HBV incidence, an 80% reduction in HCV incidence and a 65% reduction in mortality by 2030, with respect to the baseline situation in 2015.2World Health OrganizationGlobal Health Sector Strategy on Viral Hepatitis 2016–2021. Towards Ending Viral Hepatitis. WHO, Geneva2016Google Scholar Based on our estimations, a 46·1-60·5% reduction in HBV and HCV mortality is projected in 2030. However, the WHO relative targets disadvantage countries like Japan with an ageing population and a low prevalence of HBV and HCV before 2015.38Polaris Observatory CollaboratorsThe case for simplifying and using absolute targets for viral hepatitis elimination goals.J Viral Hepat. 2021; 28: 12-19Google Scholar Recently, the WHO issued new guidelines recommending the use of absolute impact targets along with programmatic targets.39World Health OrganizationInterim Guidance for Country Validation of Viral Hepatitis Elimination. WHO, Geneva2021Google Scholar The use of these targets will better assist in assessing Japan's progress towards eliminating viral hepatitis.
We assumed that new chronic HBV infections in Japan are rare, considering the successful implementation of the selective countermeasures for preventing MTCT and the low rate of horizontal infections ( although father-to-child and in-utero infections are possible).6Shiraki K. Perinatal transmission of hepatitis B virus and its prevention.J Gastroenterol Hepatol. 2000; 15 ( Suppl): E11-E15Google Scholar,7Koyama T. Matsuda I. Sato S. Yoshizawa H. Prevention of perinatal hepatitis B virus transmission by combined passive-active immunoprophylaxis in Iwate, Japan ( 1981–1992) and epidemiological evidence for its efficacy.Hepatol Res. 2003; 26: 287-292Google Scholar,22Terrault N.A. Levy M.T. Cheung K.W. Jourdain G. Viral hepatitis and pregnancy.Nat Rev Gastroenterol Hepatol. 2021; 18: 117-130Google Scholar,23Hirota T. Ohno N. Yano K. Father-to-child transmission of hepatitis B virus.Kanzo. 1987; 28: 427-432Google Scholar The situation is different in countries with high endemicity. For instance, in Taiwan, where the prevalence of HBsAg was high ( > 8%), a selective prevention approach was first used in 1984, with vaccination of infants born to HBsAg-positive mothers, and administration of HBIG to those born from mothers positive to HBeAg. Then, in 1986, the vaccination was extended to all children, irrespective of the mother's HBV status, leading to a dramatic decrease in the HBV prevalence and incidence of HCC in Taiwan.41Chang M.H. Chen C.J. Lai M.S. et al.Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. Taiwan childhood hepatoma study group.N Engl J Med. 1997; 336: 1855-1859Google Scholar This highlights that in countries with high endemicity, especially in the Western Pacific Region, prevention of both vertical and horizontal HBV transmission is required to reduce the incidence of chronic HBV infections.6Shiraki K. Perinatal transmission of hepatitis B virus and its prevention.J Gastroenterol Hepatol. 2000; 15 ( Suppl): E11-E15Google Scholar However, there is still a risk of immunoprophylaxis failure with HBV genotype C and in women with high HBV viral load.42Wen W.H. Chen H.L. Ni Y.H. et al.Secular trend of the viral genotype distribution in children with chronic hepatitis B virus infection after universal infant immunization.Hepatology. 2011; 53: 429-436Google Scholar To further assist countries in achieving the elimination of MTCT of HBV, WHO has issued guidelines recommending the use of antivirals during pregnancy for HBV-infected women with high DNA level ( > 200,000 IU/mL) or HBeAg-positive, in addition to three-dose hepatitis B vaccination in all infants ( including timely birth dose), and HBIG to those born from HBsAg-positive mothers if available.40World Health OrganizationPrevention of Mother-to-Child Transmission of Hepatitis B Virus: Guidelines on Antiviral Prophylaxis in Pregnancy. WHO, Geneva2020Google Scholar
This study is limited by several factors. First, the simulation parameters were assumed to be constant and did not consider future improvements in HBV treatment or hepatitis and liver cancer policies that may be introduced. Therefore, the future burden of hepatitis virus could be lower than our predictions. Also, the number of chronic HBV infections was estimated to be rare, based on studies discussing HBV transmission routes in Japan and the effectiveness of the countermeasures to prevent MTCT of HBV. If the number of chronic HBV infections changes due to various circumstances ( such as a war), it is necessary to reconsider the calculation. Second, the Markov model did not take into account the lost to follow-up among those engaged in care. Third, the prevalence of HBV and HCV in the general population was approximated based on the prevalence of HBV and HCV among first-time blood donors. First-time blood donors undergo a pre-screening for hepatitis infection, which may underestimate the actual prevalence. However, although the pre-screening questionnaire asks about piercings, tattoos, injecting drug use, and sexual contact with chronically infected persons, more than 60% of new HCV cases reported during infectious disease surveillance from 1999 to 2009 have no known cause.43National Institute of Infectious DiseasesInfectious Disease Surveillance Center in Japan: Hepatitis C, April 1999 to February 2011 ( Japanese). National Institute of Infectious Diseases, 2011Google Scholar Therefore, although this is an underestimate, it is reasonable to approximate the prevalence in the general population by the prevalence in first-time blood donors. Forth, the proportions of DAA therapy among HCV patients with CH and C-LC were based on actual data from the NDB in 2015. The rate of DAA use is likely to increase over the coming years. Sensitivity analysis showed that if the rate of DAA therapy in patients with CH increases to 90%, the total number of people with chronic HCV will be 465,304 in 2030, and 339,602 in 2035. It is worth noting that given the restrictive measures implemented by the Japanese government in response to the COVID-19 pandemic, the rate of hospital visits and DAA treatment could be affected, which would negatively impact the future number of chronic infections.
In conclusion, although the number of chronic HBV and HCV infections in Japan is expected to decrease, challenges in controlling hepatitis remain. Along with the control strategies already in place, achieving the WHO goal of eliminating hepatitis will require improved and innovative screening approaches and linkage to care of people infected with HCV and new therapies that allow for a complete cure of HBV.
The dataset used and analyzed in the current study is available from the corresponding author on reasonable request.
JT, TA, AK, MOhi conceived and designed the study and the data anlysis concept. JT, MS, MOha acquired the data. TA, AK, MOhi, MW, AS analysed the data. JT, TA, SO, MW, MS, MOha interpreted the data. SO, TA, JT, TK, MOha, LH drafted the manuscript. All authors read and approved the final version of the manuscript.
The authors declare no conflict of interest.
This study was conducted as part of the Policy Research for Hepatitis Measures of the Ministry of Health, Labour and Welfare ( MHLW) in Japan and supported by the MHLW Sciences Research Grants ( No. JPMH19HC1001). We thank the Japanese Red Cross Society for their support of this study.
Parts of this study were presented at the 51st International Liver Congress of the European Association for the Study of the Liver ( EASL) in Barcelona ( Spain) in 2016, the Asian Pacific Association for the Study of Liver ( APASL) conference in Tokyo ( Japan) in 2016, The Liver Meeting in Washington ( USA) in 2016, and at the 24th International Symposium on Hepatitis C virus and Related Viruses ( HCV2017) in Massachusetts ( USA) in 2017.
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The pandemic and the great awakening in the management of acute hypoxaemic respiratory failure - The Lancet Respiratory Medicine | The ability to provide invasive mechanical ventilation ( IMV) and high-quality, supportive intensive care was substantially limited during the peak of the pandemic because of the unprecedented demand for intensive care unit ( ICU) resources. As a result, clinicians turned towards less invasive and innovative approaches to manage patients with acute hypoxaemic respiratory failure. Techniques such as awake prone positioning of non-intubated patients, a seemingly simple approach that was largely only tested in observational studies before the pandemic, were used.1Weatherald J Norrie J Parhar KKS Awake prone positioning in COVID-19: is tummy time ready for prime time?.Lancet Respir Med. 2021; 9: 1347-1349Google Scholar The positive physiological benefits of prone positioning seen in patients on IMV, such as improved oxygenation, homogenisation of transpulmonary pressure, decreased lung compression, and improved ventilation–perfusion matching,2Pelosi P Brazzi L Gattinoni L Prone position in acute respiratory distress syndrome.Eur Respir J. 2002; 20: 1017-1028Google Scholar prompted adjunctive use of awake prone positioning as a strategy to avoid IMV and ICU admission in patients with COVID-19-related acute hypoxaemic respiratory failure.
In The Lancet Respiratory Medicine, Li and colleagues3Li J Luo J Pavlov I et al.Awake prone positioning for non-intubated patients with COVID-19-related acute hypoxaemic respiratory failure: a systematic review and meta-analysis.Lancet Respir Med. 2022; ( published online March 16.) https: //doi.org/10.1016/S2213-2600 ( 22) 00043-1Google Scholar report the findings of a systematic review and meta-analysis investigating the effects of awake prone positioning in non-intubated patients with COVID-19-related acute hypoxaemic respiratory failure. Awake prone positioning significantly reduced the need for intubation with a trial-sequential analysis projecting a relative risk reduction of 16%. However, awake prone positioning did not reduce mortality and ICU admission rates. Furthermore, awake prone positioning only reduced the need for intubation among patients requiring advanced respiratory support ( high-flow nasal cannula or non-invasive ventilation) and in those who underwent awake prone positioning in an ICU setting. The authors hypothesise that these results might be due to a higher incidence of intubation in this homogeneous group of patients contributing greater statistical power and precision, and better health-care worker to patient ratios in the ICU, leading to better patient adherence with awake prone positioning. Given that some studies were terminated early, the aggregation of the current data through meta-analysis and trial-sequential analysis will help inform clinicians about the potential benefits and harms of awake prone positioning.
However, there are some questions that arise from these findings: should all patients with COVID-19-related acute hypoxaemic respiratory failure receive awake prone positioning, and should it only be performed in an ICU setting? Given that these patients have significant hypoxaemia and limited physiological reserve, awake prone positioning in patients requiring advanced respiratory support should ideally be performed in an ICU to minimise the risks to the patient. However, this should be balanced with resource-allocation issues such as ICU bed availability and staffing. This calls for an integrated, multidisciplinary team approach and the development of clear management pathways for patients with acute hypoxaemic respiratory failure, in which early, adjunctive awake prone positioning is part of the continuum of care along with other respiratory supports and agreed criteria for ICU admission and IMV. Two factors might partly account for the absence of mortality benefit in the RCT analysis: first, a low statistical power given the low event rate; second, confounding by the timing of intubation. Defining the timepoint when the risks of combining less-invasive respiratory supports and awake prone positioning to delay endotracheal intubation and IMV outweigh the benefits of avoiding IMV in an individual patient is challenging.4Cruces P Retamal J Hurtado DE et al.A physiological approach to understand the role of respiratory effort in the progression of lung injury in SARS-CoV-2 infection.Crit Care. 2020; 24: 494Google Scholar
How should we design meaningful clinical trials to inform the management of patients with acute hypoxaemic respiratory failure in non-intubated, heterogeneous groups of patients with or without COVID-19? The absence of a research grade definition for acute hypoxaemic respiratory failure, the complexity of developing universally agreed triggers for IMV, and developing core outcome measures that look beyond the need for intubation and mortality are all substantial limitations to designing clinical trials. Although it is challenging, we should consider devising a syndromic definition based on a constellation of validated clinical criteria to risk stratify acute hypoxaemic respiratory failure resulting from a variety of causes. This all encompassing approach might facilitate clinical trials, but it might also reduce the ability of clinicians to personalise supportive care. We should consider the following approaches in regard to clinical trials that investigate the adjunctive use of awake prone positioning in patients with acute hypoxaemic respiratory failure. There appears to be a dose–response association between awake prone positioning and treatment success; 5Ehrmann S Li J Ibarra-Estrada M et al.Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial.Lancet Respir Med. 2021; 9: 1387-1395Google Scholar selecting patients with better adherence to treatment protocols and creating an environment that promotes such adherence might increase the treatment effect. Equally, selecting patients with a higher risk of the outcome of interest—eg, those requiring advanced respiratory support—and excluding those in whom there is poor early improvement in oxygenation following awake prone positioning might enable further enrichment of trials.6Caputo ND Strayer RJ Levitan R Early self-proning in awake, non-intubated patients in the emergency department: a single ED's experience during the COVID-19 pandemic.Acad Emerg Med. 2020; 27: 375-378Google Scholar, 7Thompson AE Ranard BL Wei Y Jelic S Prone positioning in awake, nonintubated patients with COVID-19 hypoxemic respiratory failure.JAMA Intern Med. 2020; 180: 1537-1539Google Scholar
The intention of avoiding endotracheal intubation and IMV with the use of less-invasive respiratory supports and awake prone positioning should not be driven by resource constraints alone. These supports might be a viable option, especially in patients who are unlikely to benefit from IMV. Even in non-pandemic times, IMV adds substantial costs to health care,8Wunsch H Linde-Zwirble WT Angus DC Hartman ME Milbrandt EB Kahn JM The epidemiology of mechanical ventilation use in the United States.Crit Care Med. 2010; 38: 1947-1953Google Scholar and the risk–benefit ratio of IMV varies considerably with age, comorbidities, and baseline functional status. It is time that we looked beyond short-term survival and define which populations of patients with acute hypoxaemic respiratory failure are most likely to meaningfully benefit from IMV. In addition to drawing from the evidence base, engagement with patients is central to making this decision.
The pandemic has certainly allowed us to reimagine the future management of acute hypoxaemic respiratory failure. There are many approaches clinicians can take to delay IMV or avoid IMV altogether. The risk–benefit ratio and the costs of this approach requires investigation in clinical trials. The majority of patients with acute hypoxaemic respiratory failure who receive IMV do so because of worsening hypoxaemia and respiratory muscle fatigue from an increased work of breathing.9Frat JP Ragot S Coudroy R et al.Predictors of intubation in patients with acute hypoxemic respiratory failure treated with a noninvasive oxygenation strategy.Crit Care Med. 2018; 46: 208-215Google Scholar In addition to awake prone positioning, pharmacological adjuncts such as nitric oxide gas, which were introduced in attempt to improve oxygenation in non-intubated patients during the pandemic, need further testing in clinical trials. Environmental modifications, staff education, patient compliance, and the pharmacological management of anxiety and agitation are all critical components to the success of awake strategies that aim to avoid IMV. Minimising the reliance on the diseased native lungs for gas exchange with the use of extracorporeal techniques merits consideration too. For example, extracorporeal carbon dioxide removal might allow better control of respiratory effort and in select patients might help prevent IMV. Awake extracorporeal membrane oxygenation10Langer T Santini A Bottino N et al. “ Awake ” extracorporeal membrane oxygenation ( ECMO): pathophysiology, technical considerations, and clinical pioneering.Crit Care. 2016; 20: 150Google Scholar without IMV might be a viable option in select patients. Moving forward, although IMV is inevitable in some patients, there might be room for better integration and greater personalisation of respiratory supports that allow patients to be awake, ambulatory, and rehabilitate while maintaining their autonomy.
A concerted, collaborative undertaking of research across disciplines is needed to tackle acute hypoxaemic respiratory failure globally. Inequities in health-system access is morally confronting. Future acute hypoxaemic respiratory failure research should also focus on low-cost, high-value respiratory supports, such as awake prone positioning, which are tailored for resource poor settings. Hopefully, in the post-pandemic world, we will be one step closer to offering more personalised, equitable, value-driven, and evidence-based respiratory supports for patients with acute hypoxaemic respiratory failure.
We declare no competing interests. KS acknowledges research support from Metro North Hospital and Health Service.
Awake prone positioning for non-intubated patients with COVID-19-related acute hypoxaemic respiratory failure: a systematic review and meta-analysisIn patients with COVID-19-related acute hypoxaemic respiratory failure, awake prone positioning reduced the need for intubation, particularly among those requiring advanced respiratory support and those in ICU settings. Awake prone positioning should be used in patients who have acute hypoxaemic respiratory failure due to COVID-19 and require advanced respiratory support or are treated in the ICU. Full-Text PDF | tech |
Clinical characteristics of the first three waves of hospitalised patients with COVID-19 in Japan prior to the widespread use of vaccination: a nationwide observational study - The Lancet Regional Health – Western Pacific | BackgroundBefore widespread coronavirus disease ( COVID-19) vaccinations, Japan experienced three COVID-19 epidemic waves. This study aimed to evaluate the characteristics of hospitalised COVID-19 patients and reveal temporal changes.MethodsThis study included 33,554 hospitalised patients with COVID-19 from 553 healthcare facilities. Data were analysed by age group and epidemic wave ( first wave, 01/01/2020–05/31/2020; second wave, 06/01/2020–10/31/2020; and third wave, 11/01/2020–03/31/2021).FindingsBy age group, 3% ( under 18), 22% ( young), 34% ( middle-aged), and 41% ( older patients) were aged 0-17, 18-39, 40-64, and > 65 years; while 16%, 35%, and 49% were in the first, second, and third wave, respectively. The patients’ overall median age ( 58 years; interquartile range, 39–74) was lowest and highest during the second and third waves, respectively. The frequency of any comorbidity was lowest and highest during the second ( 44·5%) and third ( 63·6%) waves, respectively. The symptoms at admission and exposure history differed considerably with age. The overall case fatality rate ( 5%) was highest among older patients ( 11·4%). Case fatality rate was highest and lowest during the first ( 7·3%) and second ( 2·8%) waves, respectively. Medication use changed over time.InterpretationAlthough the overall case fatality rate remained relatively low, it was more than twice as high among older patients. After adjusting for age and comorbidities, the risk of death was highest in the first wave.FundingThis work was supported by the Ministry of Health, Labour and Welfare “ Research on Emerging and Re-emerging Infectious Diseases and Immunization ” 19HA1003 ].
Before widespread coronavirus disease ( COVID-19) vaccinations, Japan experienced three COVID-19 epidemic waves. This study aimed to evaluate the characteristics of hospitalised COVID-19 patients and reveal temporal changes.
This study included 33,554 hospitalised patients with COVID-19 from 553 healthcare facilities. Data were analysed by age group and epidemic wave ( first wave, 01/01/2020–05/31/2020; second wave, 06/01/2020–10/31/2020; and third wave, 11/01/2020–03/31/2021).
By age group, 3% ( under 18), 22% ( young), 34% ( middle-aged), and 41% ( older patients) were aged 0-17, 18-39, 40-64, and > 65 years; while 16%, 35%, and 49% were in the first, second, and third wave, respectively. The patients’ overall median age ( 58 years; interquartile range, 39–74) was lowest and highest during the second and third waves, respectively. The frequency of any comorbidity was lowest and highest during the second ( 44·5%) and third ( 63·6%) waves, respectively. The symptoms at admission and exposure history differed considerably with age. The overall case fatality rate ( 5%) was highest among older patients ( 11·4%). Case fatality rate was highest and lowest during the first ( 7·3%) and second ( 2·8%) waves, respectively. Medication use changed over time.
Although the overall case fatality rate remained relatively low, it was more than twice as high among older patients. After adjusting for age and comorbidities, the risk of death was highest in the first wave.
This work was supported by the Ministry of Health, Labour and Welfare “ Research on Emerging and Re-emerging Infectious Diseases and Immunization ” 19HA1003 ].
Research in context Evidence before this studyThe novel coronavirus infection ( COVID-19) has become a public health threat worldwide; however, the epidemiological characteristics of patients differ significantly between Western countries and Asia. Although multiple epidemic waves of COVID-19 have occurred in Japan, there has been no study using nationwide registry that have clarified changes in the epidemiological characteristics of patients hospitalised for COVID-19 during the epidemic waves.We conducted a PubMed search between 1 December 2019, and 30 November 2021, for articles published in English using the keywords: ( “ COVID-19 ” OR “ SARS-CoV-2 ” OR “ novel coronavirus ” OR “ 2019-nCoV ”) AND ( “ Japan ”) AND ( “ registry ”) AND ( “ wave ”). Our search identified eight publications, of which five were related to occupational health ( two were on healthcare workers), two were on response and preparedness for COVID-19, and one was on the epidemiology of subarachnoid haemorrhage during the COVID-19 pandemic. We found no report that used registry data to determine the epidemiological status of hospitalised patients during the epidemic waves in Japan. We also conducted a PubMed search using the keywords: ( `` COVID-19 '' OR `` SARS-CoV-2 '' OR `` novel coronavirus '' OR `` 2019-nCoV '') AND ( `` Japan '') AND ( `` wave '') AND ( `` comparison ''). Our search identified 11 papers. Of these, four reported on prediction using mathematical models in Japan; the number of infected people and deaths using artificial intelligence in multiple countries; mortality statistics; and influence of population density, temperature, and absolute humidity on the spread and decay durations of COVID-19. Three studies focused on severe acute respiratory syndrome coronavirus 2 ( SARS-CoV-2) genome sequences, cross-neutralizing activity against SARS-CoV-2 variants, and SARS-CoV-2 PCR positivity. Two studies examined the effect of COVID-19 on swimming and the step counts. One was a single-centre comparison of the first-third waves with the fourth wave. Another was an international comparison of perception of and anxiety about COVID-19 infection and risk behaviours. Added value of this studyTo the best of our knowledge, this is the largest study to date describing the changes of clinical epidemiological characteristics of inpatients with COVID-19 observed during the three epidemic waves in Japan that occurred prior to mass vaccination. Although the overall case fatality rate remained low, the case fatality rate was approximately twice as high among older patients and varied with epidemic wave. Notably, case fatality rates reduced in the third wave compared to the first wave despite an increase in the median age and comorbidity. The medications and supportive care for COVID-19 changed over time in Japan. The epidemiological and clinical characteristics differed greatly among each age group. Implications of all available evidenceWe present important epidemiological information in an Asian population with lower comorbidities than other populations. As vaccination rates and virus variants increase, changes in the epidemiological characteristics of COVID-19 are inevitable. Our findings could provide baseline data to track these changes. After adjusting for the age and comorbidities, the risk of death was highest in the first wave. The case fatality rate among older adults remained high, suggesting the need to target this age group for prevention and treatment.
The novel coronavirus infection ( COVID-19) has become a public health threat worldwide; however, the epidemiological characteristics of patients differ significantly between Western countries and Asia. Although multiple epidemic waves of COVID-19 have occurred in Japan, there has been no study using nationwide registry that have clarified changes in the epidemiological characteristics of patients hospitalised for COVID-19 during the epidemic waves.
We conducted a PubMed search between 1 December 2019, and 30 November 2021, for articles published in English using the keywords: ( “ COVID-19 ” OR “ SARS-CoV-2 ” OR “ novel coronavirus ” OR “ 2019-nCoV ”) AND ( “ Japan ”) AND ( “ registry ”) AND ( “ wave ”). Our search identified eight publications, of which five were related to occupational health ( two were on healthcare workers), two were on response and preparedness for COVID-19, and one was on the epidemiology of subarachnoid haemorrhage during the COVID-19 pandemic. We found no report that used registry data to determine the epidemiological status of hospitalised patients during the epidemic waves in Japan. We also conducted a PubMed search using the keywords: ( `` COVID-19 '' OR `` SARS-CoV-2 '' OR `` novel coronavirus '' OR `` 2019-nCoV '') AND ( `` Japan '') AND ( `` wave '') AND ( `` comparison ''). Our search identified 11 papers. Of these, four reported on prediction using mathematical models in Japan; the number of infected people and deaths using artificial intelligence in multiple countries; mortality statistics; and influence of population density, temperature, and absolute humidity on the spread and decay durations of COVID-19. Three studies focused on severe acute respiratory syndrome coronavirus 2 ( SARS-CoV-2) genome sequences, cross-neutralizing activity against SARS-CoV-2 variants, and SARS-CoV-2 PCR positivity. Two studies examined the effect of COVID-19 on swimming and the step counts. One was a single-centre comparison of the first-third waves with the fourth wave. Another was an international comparison of perception of and anxiety about COVID-19 infection and risk behaviours.
To the best of our knowledge, this is the largest study to date describing the changes of clinical epidemiological characteristics of inpatients with COVID-19 observed during the three epidemic waves in Japan that occurred prior to mass vaccination. Although the overall case fatality rate remained low, the case fatality rate was approximately twice as high among older patients and varied with epidemic wave. Notably, case fatality rates reduced in the third wave compared to the first wave despite an increase in the median age and comorbidity. The medications and supportive care for COVID-19 changed over time in Japan. The epidemiological and clinical characteristics differed greatly among each age group.
We present important epidemiological information in an Asian population with lower comorbidities than other populations. As vaccination rates and virus variants increase, changes in the epidemiological characteristics of COVID-19 are inevitable. Our findings could provide baseline data to track these changes. After adjusting for the age and comorbidities, the risk of death was highest in the first wave. The case fatality rate among older adults remained high, suggesting the need to target this age group for prevention and treatment.
Coronavirus disease ( COVID-19) has been prevalent in Japan since January 2020 with substantial variation in the number of cases. As of August 2021, the fifth wave of the epidemic is underway.1Ritchie H, Mathieu E, Rodés-Guirao L, et al. Coronavirus Pandemic ( COVID-19) – Japan: coronavirus pandemic country profile. Published online at OurWorldInData.org. 2020. Retrieved from: https: //ourworldindata.org/coronavirus/country/japan? country=∼JPN. Accessed 10 December 2021.Google Scholar During this period, there have been various changes in approaches to COVID-19 prevention, diagnosis, and treatment strategies, including changes in the criteria for hospitalisation, and the start of COVID-19 vaccination.
Various drugs, including those with uncertain efficacy at the time, were initially used in Japan; 2Matsunaga N Hayakawa K Terada M et al.Clinical epidemiology of hospitalized patients with COVID-19 in Japan: report of the COVID-19 REGISTRY JAPAN.Clin Infect Dis. 2020; Google Scholar however, emerging evidence continues to influence domestic guidelines and clinical practice.3Clinical Practice Guideline Review Committee. COVID-19 clinical practice guideline ver 6.0 2021. April 1, 2020. Available at: https: //www.mhlw.go.jp/content/000851082.pdf. Accessed 10 December 2021.Google Scholar The criteria for hospitalisation have also changed. In the beginning of the pandemic, almost all patients with COVID-19 were hospitalised; however, as the spread of the infection progressed, the target population for hospitalisation was changed to patients with or at risk of severe disease.4Yamada G Hayakawa K Matsunaga N et al.Predicting respiratory failure for COVID-19 patients in Japan: a simple clinical score for evaluating the need for hospitalisation.Epidemiol Infect. 2021; 149: e175https: //doi.org/10.1017/S0950268821001837Google Scholar
In Japan, COVID-19 vaccination began in February 2021, and healthcare workers and older adults were prioritised. As of 31 March 2021, the proportion of people fully vaccinated against COVID-19 was 0·1% ( n=125,580) ( partly vaccinated, 0·7% [ n=877,157 ]) of the total population of Japan.5Ritchie H, Mathieu E, Rodés-Guirao L,, et al. Coronavirus Pandemic ( COVID-19) – Japan: Coronavirus ( COVID-19) Vaccinations. Published online at OurWorldInData.org. 2020. Retrieved from: https: //ourworldindata.org/covid-vaccinations? country=∼JPN. Accessed 10 December 2021.Google Scholar
The characteristics of hospitalised patients with COVID-19 in Japan during the early phase of the epidemic were previously reported using a nationwide registry. The epidemiological characteristics were different from those in Western countries, with lower case fatality rate and comorbidity frequency in our cohort.2Matsunaga N Hayakawa K Terada M et al.Clinical epidemiology of hospitalized patients with COVID-19 in Japan: report of the COVID-19 REGISTRY JAPAN.Clin Infect Dis. 2020; Google Scholar To the best of our knowledge, no comprehensive analysis examining whether case fatality rate and clinical epidemiological characteristics had changed during subsequent epidemic waves was conducted. A previous study compared patients by severity of illness,2Matsunaga N Hayakawa K Terada M et al.Clinical epidemiology of hospitalized patients with COVID-19 in Japan: report of the COVID-19 REGISTRY JAPAN.Clin Infect Dis. 2020; Google Scholar but not by age group. Little is known regarding the effect of repeated epidemic waves on the clinical epidemiology of COVID-19 inpatients in Asian countries, where individuals have fewer comorbidities and lower body mass index ( BMI) measures than individuals in Western countries.6World Health Organization. Mean body mass index trends among adults, age-standardized ( kg/m²). Estimates by country. 2017. Available at: https: //apps.who.int/gho/data/view.main.CTRY12461? lang=en. Accessed 10 December 2021.Google Scholar
This study aimed to determine the characteristics of hospitalised COVID-19 patients in each epidemic wave and different age groups prior to widespread vaccination.
This was an observational study. Healthcare facilities that voluntarily participated in the COVID-19 Registry Japan ( COVIREGI-JP) enrolled the patients. Research collaborators in each facility manually input the data into the registry. The inclusion criteria for enrolment were ( i) a positive severe acute respiratory syndrome coronavirus 2 ( SARS-CoV-2) test result7Ministry of Health, Labour and Welfare. Notification of physicians and veterinarians under the Infectious Diseases Act. Available at: https: //www.mhlw.go.jp/bunya/kenkou/kekkaku-kansenshou11/01-shitei-01.html. Accessed 10 December 2021.Google Scholar and ( ii) inpatient treatment at a healthcare facility. COVIREGI-JP details are described elsewhere.2Matsunaga N Hayakawa K Terada M et al.Clinical epidemiology of hospitalized patients with COVID-19 in Japan: report of the COVID-19 REGISTRY JAPAN.Clin Infect Dis. 2020; Google Scholar,8National Center for Global Health and Medicine. COVID-19 REGISTRY JAPAN. Available at: https: //covid-registry.ncgm.go.jp/. Accessed 10 December 2021.Google Scholar In this analysis, we also included the hospitalisation episodes of patients who were transferred from other facilities and who met the aforementioned inclusion criteria.
We modified the case report form of the International Severe Acute Respiratory and Emerging Infection Consortium ( ISARIC) to enable the collection of clinical epidemiological information and treatment data in Japan.9International Severe Acute Respiratory and Emerging Infection Consortium. COVID-19 clinical research resources. COVID-19 Clinical Research Resources. Available at: https: //isaric.tghn.org/covid-19-clinical-research-resources/. Accessed 10 December 2021.Google Scholar The study data were collected and managed using Research Electronic Data Capture ( REDCap), a secure web-based data capture application hosted at the Japan Clinical Research Assist Center ( JCRAC) of the National Center for Global Health and Medicine ( NCGM).10Harris PA Taylor R Thielke R Payne J Gonzalez N Conde JG. Research electronic data capture ( REDCap) –a metadata-driven methodology and workflow process for providing translational research informatics support.J Biomed Inform. 2009; 42: 377-381https: //doi.org/10.1016/j.jbi.2008.08.010Google Scholar
The COVIREGI-JP was started on 2 March 2020; however, data could be entered retrospectively. We used data for patients who were admitted on or before 31 March 2021, and whose data, including all of the following major items, had been entered and fixed ( i.e., the data of these major items were fixed and the facility was unable to make any more modification) as of 30 April 2021: demographics and epidemiological characteristics, comorbidities, signs and symptoms at admission, outcome at discharge, supportive care, history of drug administration, and complications during hospitalisation. Available number of cases for each parameter differed due to missing data. If an “ Unknown ” option was selected instead of none of the options selected, “ Unknown ” was not treated as missing data; it was counted separately. Only the following parameters included “ Unknown ” as an option: exposure within 14 days, smoking/drinking history, symptoms, and complications during admission. The number of patients for parameters with “ Unknown ” information are listed in Table 1 or in Supplementary Table 1.Table 1Patient demographics and clinical characteristics on admissionAge categoryWave categoryNumber of casesSubcategoriesTotalUnder 18 ( 0–17 years) Young ( 18–39 years) Middle age ( 40–64 years) Older ( ≥65 years) Wave 1Wave 2Wave 3DemographicsMale sex33,55118,985 ( 56·6) 608 ( 55·1) 4030 ( 55·2) 7424 ( 64·9) 6917 ( 50·5) 3139 ( 58·5) 6784 ( 58) 9062 ( 55) Female sex14,566 ( 43.4) 496 ( 44.9) 3277 ( 44.8) 4020 ( 35.1) 6770 ( 49.5) 2233 ( 41.5) 4908 ( 42) 7428 ( 45) Age ( median) [ IQR ], years33,54258 [ 39, 74 ] 9 [ 3, 14 ] 28 [ 23, 34 ] 53 [ 47, 58 ] 77 [ 71, 85 ] 56 [ 40, 71 ] 50 [ 30, 69 ] 64 [ 47, 78 ] Wave33,554First5372 ( 16) 109 ( 9·9) 1175 ( 16·1) 2138 ( 18·7) 1949 ( 14·2) Second11,692 ( 34·8) 459 ( 41·6) 3772 ( 51·6) 3924 ( 34·3) 3532 ( 25·8) Third16,490 ( 49·1) 536 ( 48·6) 2360 ( 32·3) 5382 ( 47) 8206 ( 60) Japanese ethnicity33,19031,680 ( 95·5) 955 ( 87·5) 6561 ( 90·7) 10,747 ( 95) 13,407 ( 99) 5125 ( 95·7) 10,950 ( 94·1) 15,605 ( 96·3) Former or current smoker33,46011,721 ( 35) 12 ( 1.1) 2399 ( 32.9) 4977 ( 43·6) 4332 ( 31·7) 1882 ( 35·2) 4420 ( 38) 5419 ( 32·9) Alcohol consumption aDaily, ≥3 cans of beer per day; occasional includes daily alcohol intake of < 3 cans beer per day.32,866Daily2297 ( 7) 2 ( 0·2) 589 ( 8·2) 1130 ( 10·1) 576 ( 4·3) 347 ( 7·3) 1049 ( 9) 901 ( 5·5) Occasional10,525 ( 32) 7 ( 0·6) 2941 ( 41·2) 4553 ( 40·9) 3021 ( 22·4) 1436 ( 30·1) 4157 ( 35·7) 4932 ( 30) BMI ( median) [ IQR ], kg/m227,18023·3 [ 20·7, 26·3 ] 18·2 [ 16, 20·7 ] 22·4 [ 20·1, 25·7 ] 24·7 [ 22·1, 27·8 ] 22·8 [ 20·3, 25·3 ] 23·1 [ 20·5, 26 ] 23·1 [ 20·5, 26·3 ] 23·4 [ 20·8, 26·4 ] ImmunosuppressionbImmunosuppression includes neutropenia ( < 500 neutrophils/μL); glucocorticoid/steroid use within 1 month ( doses greater or equal to an equivalent of 20 mg of prednisone per day for at least 1 month); chemotherapy, radiation therapy, or immunosuppressant use ( such as antitumor necrosis factor α therapy, anti-IL-6 receptor/anti-CD20 monoclonal antibodies, selective T-cell co-stimulation blocker, methotrexate, tacrolimus) in the past 3 months; and/or post-transplantation, asplenia, or primary immunodeficiency syndrome. Multiple immunosuppressants were used in some cases.32,840708 ( 2·2) 8 ( 0·7) 57 ( 0·8) 212 ( 1·9) 431 ( 3·2) 145 ( 2·8) 199 ( 1·7) 364 ( 2·3) Exposure within 14 daysTravel to COVID-19 epidemic countries33,329564 ( 1·7) 36 ( 3·3) 189 ( 2·6) 196 ( 1·7) 143 ( 1·1) 345 ( 6·4) 132 ( 1·1) 87 ( 0·5) Close contact with COVID-19 casesc “ Close contact ” was defined as in the International Severe Acute Respiratory and Emerging Infection Consortium case record form.933,35818,269 ( 54·8) 914 ( 83) 3671 ( 50·5) 5475 ( 48·2) 8203 ( 60·3) 3035 ( 56·5) 6039 ( 51·8) 9195 ( 56·3) Unknown3915 ( 11·7) 40 ( 3·6) 793 ( 10·9) 1468 ( 12·9) 1614 ( 11·9) 654 ( 12·2) 1212 ( 10·4) 2049 ( 12·6) Contact details33,554Family6968 ( 20·8) 713 ( 64·6) 948 ( 13) 2178 ( 19) 3128 ( 22·9) 912 ( 17) 2273 ( 19·4) 3783 ( 22·9) Workplace3354 ( 10) 2 ( 0·2) 1288 ( 17·6) 1656 ( 14·5) 407 ( 3) 601 ( 11·2) 1265 ( 10·8) 1488 ( 9) Healthcare facility4785 ( 14·3) 2 ( 0·2) 346 ( 4·7) 675 ( 5·9) 3760 ( 27·5) 913 ( 17) 1049 ( 9) 2823 ( 17·1) Educational facility253 ( 0·8) 143 ( 13) 75 ( 1) 24 ( 0·2) 10 ( 0·1) 15 ( 0·3) 108 ( 0·9) 130 ( 0·8) Meals with more than 3 persons ( excl. family members) 32,7834643 ( 14·2) 95 ( 8·7) 1605 ( 22·5) 1595 ( 14·4) 1346 ( 10) 539 ( 11·2) 2030 ( 17·4) 2074 ( 12·7) Unknown9554 ( 29·1) 204 ( 18·7) 2050 ( 28·7) 3537 ( 31·9) 3763 ( 28) 1951 ( 40·4) 3218 ( 27·6) 4385 ( 26·9) Stay in a closed and crowded spacedClose contact in closed and crowded spaces, include sports gyms, live music clubs, karaokes, game centers, buffets, indoor parties, conferences, or nightclubs/bars.32,7614533 ( 13·8) 74 ( 6·8) 1645 ( 23·1) 1561 ( 14·1) 1250 ( 9·3) 658 ( 13·6) 2177 ( 18·7) 1698 ( 10·4) Unknown8745 ( 26·7) 181 ( 16·6) 1960 ( 27·5) 3389 ( 30·6) 3215 ( 23·9) 1683 ( 34·9) 2875 ( 24·7) 4187 ( 25·7) OccupationHealthcare worker32,8111753 ( 5·3) 3 ( 0·3) 667 ( 9·3) 894 ( 8) 188 ( 1·4) 455 ( 9·4) 507 ( 4·3) 791 ( 4·9) Restaurant worker32,7531128 ( 3·4) 1 ( 0·1) 423 ( 5·9) 427 ( 3·8) 277 ( 2·1) 164 ( 3·4) 555 ( 4·8) 409 ( 2·5) Specific service workereIncluded nightlife business workers at bars and pubs, host and hostess clubs, nightclubs, and other similar businesses.2832,744775 ( 2·4) 2 ( 0·2) 503 ( 7·1) 200 ( 1·8) 70 ( 0·5) 126 ( 2·6) 446 ( 3·8) 203 ( 1·2) Conditions at admissionfFirst available data at presentation/admission within 24 hours.Days from symptom onset to hospitalisation ( Median) [ IQR ] 30,2445 [ 2, 7 ] 3 [ 1, 5 ] 4 [ 2, 7 ] 5 [ 3, 8 ] 4 [ 2, 7 ] 7 [ 4, 10 ] 4 [ 2, 7 ] 4 [ 2, 7 ] Severe condition at admission33,5549587 ( 28·6) 214 ( 19·4) 567 ( 7·8) 2906 ( 25·4) 5898 ( 43·1) 1767 ( 32·9) 2544 ( 21·8) 5276 ( 32) O2 administration method33,287Room air28,537 ( 85·7) 1045 ( 99·4) 7115 ( 98·1) 10,031 ( 88·2) 10,335 ( 76) 4417 ( 82·7) 10,451 ( 90·1) 13,669 ( 83·6) O2 administration4312 ( 13) 6 ( 0·6) 129 ( 1·8) 1174 ( 10·3) 3002 ( 22·1) 779 ( 14·6) 1025 ( 8·8) 2508 ( 15·3) BiPAP/CPAP, IMV, ECMO438 ( 1·3) 0 ( 0) 7 ( 0·1) 173 ( 1·5) 258 ( 1·9) 143 ( 2·7) 121 ( 1) 174 ( 1·1) O2 administered through4306Cannula2941 ( 68·3) 4 ( 66·7) 102 ( 79·1) 836 ( 71·4) 1998 ( 66·6) 490 ( 63) 734 ( 71·8) 1717 ( 68·5) Mask812 ( 18·9) 2 ( 33·3) 22 ( 17·1) 201 ( 17·2) 587 ( 19·6) 152 ( 19·5) 167 ( 16·3) 493 ( 19·7) Reservoir mask484 ( 11·2) 0 ( 0) 5 ( 3·9) 117 ( 10) 362 ( 12·1) 126 ( 16·2) 106 ( 10·4) 252 ( 10·1) High-flow therapy69 ( 1·6) 0 ( 0) 0 ( 0) 17 ( 1·5) 52 ( 1·7) 10 ( 1·3) 15 ( 1·5) 44 ( 1·8) Signs and symptoms on admissiongSigns and symptoms observed/reported at admission and associated with the presented episode of acute illness.Asymptomatic on admission33,0843029 ( 9·2) 320 ( 29·2) 582 ( 8·1) 621 ( 5·5) 1505 ( 11·1) 321 ( 6·5) 1183 ( 10·1) 1525 ( 9·3) Fever ( ≥37·5°C) 33,53616,208 ( 48·3) 319 ( 28·9) 2911 ( 39·9) 6222 ( 54·4) 6751 ( 49·4) 2807 ( 52·3) 5198 ( 44·5) 8203 ( 49·8) Cough33,53616,295 ( 48·6) 306 ( 27·7) 3464 ( 47·4) 6493 ( 56·8) 6025 ( 44) 2816 ( 52·5) 5228 ( 44·7) 8251 ( 50·1) Bloody sputum16,252242 ( 1·5) 2 ( 0·7) 41 ( 1·2) 95 ( 1·5) 103 ( 1·7) 43 ( 1·5) 69 ( 1·3) 130 ( 1·6) Sore throat33,5395415 ( 16·1) 133 ( 12·1) 1763 ( 24·1) 2247 ( 19·6) 1270 ( 9·3) 722 ( 13·4) 2050 ( 17·5) 2643 ( 16) Rhinorrhoea33,5393084 ( 9·2) 246 ( 22·3) 1060 ( 14·5) 1090 ( 9·5) 687 ( 5) 441 ( 8·2) 898 ( 7·7) 1745 ( 10·6) Dyspnoea33,5426941 ( 20·7) 18 ( 1·6) 988 ( 13·5) 2857 ( 25) 3078 ( 22·5) 1350 ( 25·1) 2005 ( 17·2) 3586 ( 21·8) Chest pain33,541932 ( 2·8) 4 ( 0·4) 240 ( 3·3) 448 ( 3·9) 240 ( 1·8) 182 ( 3·4) 332 ( 2·8) 418 ( 2·5) Myalgia33,5422876 ( 8·6) 21 ( 1·9) 777 ( 10·6) 1426 ( 12·5) 651 ( 4·8) 372 ( 6·9) 1005 ( 8·6) 1499 ( 9·1) Headache33,5355119 ( 15·3) 115 ( 10·4) 1721 ( 23·6) 2429 ( 21·2) 852 ( 6·2) 717 ( 13·4) 1994 ( 17·1) 2408 ( 14·6) Fatigue33,53511,700 ( 34·9) 101 ( 9·1) 2472 ( 33·8) 4795 ( 41·9) 4328 ( 31·6) 2076 ( 38·7) 3948 ( 33·8) 5676 ( 34·4) Abdominal pain33,528608 ( 1·8) 21 ( 1·9) 176 ( 2·4) 227 ( 2) 184 ( 1·3) 124 ( 2·3) 216 ( 1·8) 268 ( 1·6) Vomit33,5281230 ( 3·7) 25 ( 2·3) 302 ( 4·1) 452 ( 4) 451 ( 3·3) 207 ( 3·9) 444 ( 3·8) 579 ( 3·5) Diarrhoea33,5303156 ( 9·4) 69 ( 6·3) 818 ( 11·2) 1393 ( 12·2) 875 ( 6·4) 604 ( 11·3) 1232 ( 10·5) 1320 ( 8) Dysgeusia33,5355415 ( 16·1) 101 ( 9·1) 2238 ( 30·6) 2145 ( 18·8) 929 ( 6·8) 894 ( 16·6) 2397 ( 20·5) 2124 ( 12·9) Olfactory abnormality33,5324878 ( 14·5) 87 ( 7·9) 2219 ( 30·4) 1881 ( 16·4) 689 ( 5) 734 ( 13·7) 2239 ( 19·2) 1905 ( 11·6) Rash32,897224 ( 0·7) 6 ( 0·5) 58 ( 0·8) 101 ( 0·9) 59 ( 0·4) 38 ( 0·8) 93 ( 0·8) 93 ( 0·6) Data are presented as n (%) unless otherwise indicated.As the number of missing values differed for each parameter, the number of cases in each parameter's age/wave category was used as the denominator for calculating the percentage.Abbreviations: BiPAP/CPAP, bilevel positive airway pressure/continuous positive airway pressure; BMI, body mass index; IMV, invasive mechanical ventilation; ECMO, extracorporeal membrane oxygenation; IQR, interquartile range.a Daily, ≥3 cans of beer per day; occasional includes daily alcohol intake of < 3 cans beer per day.b Immunosuppression includes neutropenia ( < 500 neutrophils/μL); glucocorticoid/steroid use within 1 month ( doses greater or equal to an equivalent of 20 mg of prednisone per day for at least 1 month); chemotherapy, radiation therapy, or immunosuppressant use ( such as antitumor necrosis factor α therapy, anti-IL-6 receptor/anti-CD20 monoclonal antibodies, selective T-cell co-stimulation blocker, methotrexate, tacrolimus) in the past 3 months; and/or post-transplantation, asplenia, or primary immunodeficiency syndrome. Multiple immunosuppressants were used in some cases.c “ Close contact ” was defined as in the International Severe Acute Respiratory and Emerging Infection Consortium case record form.9d Close contact in closed and crowded spaces, include sports gyms, live music clubs, karaokes, game centers, buffets, indoor parties, conferences, or nightclubs/bars.e Included nightlife business workers at bars and pubs, host and hostess clubs, nightclubs, and other similar businesses.28Expert Meeting on Control of the Novel Coronavirus Disease Control. Analysis and recommendations of the response to the novel coronavirus ( COVID-19). April 1, 2020. Available at: https: //www.mhlw.go.jp/content/10900000/000620826.pdf. Accessed 10 December 2021.Google Scholarf First available data at presentation/admission within 24 hours.g Signs and symptoms observed/reported at admission and associated with the presented episode of acute illness. Open table in a new tab
Data are presented as n (%) unless otherwise indicated.
As the number of missing values differed for each parameter, the number of cases in each parameter's age/wave category was used as the denominator for calculating the percentage.
Abbreviations: BiPAP/CPAP, bilevel positive airway pressure/continuous positive airway pressure; BMI, body mass index; IMV, invasive mechanical ventilation; ECMO, extracorporeal membrane oxygenation; IQR, interquartile range.
Age was categorized and analysed in four groups as follows: ( i) under 18 ( 0–17 years), ( ii) young ( 18–39 years), ( iii) middle age ( 40–64 years), and ( iv) older patients ( ≥65 years).
COVID-19 epidemic waves were defined as follows using the admission date: ( i) first wave ( Wave 1), 01/01/2020–05/31/2020; ( ii) second wave ( Wave 2), 06/01/2020–10/31/2020; and ( iii) third wave ( Wave 3), 11/01/2020–03/31/2021.1Ritchie H, Mathieu E, Rodés-Guirao L, et al. Coronavirus Pandemic ( COVID-19) – Japan: coronavirus pandemic country profile. Published online at OurWorldInData.org. 2020. Retrieved from: https: //ourworldindata.org/coronavirus/country/japan? country=∼JPN. Accessed 10 December 2021.Google Scholar,11Saito S Asai Y Matsunaga N et al.First and second COVID-19 waves in Japan: a comparison of disease severity and characteristics.J Infect. 2021; 82: 84-123https: //doi.org/10.1016/j.jinf.2020.10.033Google Scholar For cases where the SARS-CoV-2 test date was after the admission date ( e.g., hospital-acquired COVID-19 cases), the test date was used instead of the admission date.
“ Severe disease at admission ” was defined as requiring invasive or non-invasive mechanical ventilation, supplemental oxygen, SpO2 ≤ 94% on room air, and/or tachypnoea ( respiratory rate ≥24 breaths per minute).12Beigel JH Tomashek KM Dodd LE et al.Remdesivir for the Treatment of Covid-19 – —final report.N Engl J Med. 2020; 383: 1813-1826https: //doi.org/10.1056/NEJMoa2007764Google Scholar
“ Obesity ” was defined as a body mass index ( BMI) ≥ 25 due to the small number of patients with BMIs ≥ 30.
If the patient received more than one type of oxygen support during the hospitalisation, only one higher level of oxygen support was counted ( i.e. extracorporeal membrane oxygenation ( ECMO) > invasive mechanical ventilation ( IMV) > bilevel positive airway pressure/continuous positive airway pressure ( BIPAP/CPAP) > high-flow nasal cannula > other oxygen support).
Information on SARS-CoV-2 antiviral drugs, medications with immunomodulatory and/or immunosuppressive effects against COVID-19, antibiotics, antifungal drugs, and anticoagulants was collected. These medications were included in the analysis as described in the statistical analysis section, if they were administered at least once during the hospitalisation period. If more than one drug was used in one patient, each drug was counted separately, regardless of whether they were administered concurrently. If one drug was administered during the different periods of hospitalisation, it was counted as one.
Continuous variables are described as medians and interquartile ranges ( IQRs). As the number of missing values differed for each parameter, the number of cases in each parameter's age/wavecategory was used as the denominator for calculating the percentage.
To compare the major characteristics and drug administration during hospitalisation among the waves, we conducted Kruskal-Wallis Rank Sum test for age, and chi-square test for other variables. Bonferroni correction was used for pairwise comparisons among waves ( threshold of significant difference was 0.0167), and corresponding 98.33% confidence intervals were provided. To evaluate the effect of each wave on death, we conducted a multivariable analysis using a relative risk regression model, with death during hospitalisation as the outcome. The parameters in the model were selected by referring to previous evaluations.3Clinical Practice Guideline Review Committee. COVID-19 clinical practice guideline ver 6.0 2021. April 1, 2020. Available at: https: //www.mhlw.go.jp/content/000851082.pdf. Accessed 10 December 2021.Google Scholar,13Terada M Ohtsu H Saito S et al.Risk factors for severity on admission and the disease progression during hospitalisation in a large cohort of patients with COVID-19 in Japan.BMJ Open. 2021; 11e047007Google Scholar All statistical analyses were conducted using R, version 3.5.1 ( R Core Team, Vienna, Austria).
This study was approved by the NCGM ethics review board ( NCGM-G-004232-00). Information regarding opting out of our study is available on the registry website.
The funding source was not involved in the study.
Data of 33,554 patients from 553 healthcare facilities were included in the analysis ( Figure 1). The available number of cases differed depending on each parameter due to missing data. The numbers of patients in each age category were as follows: under 18, 1104 ( 3%); young, 7307 ( 22%); middle age, 11,444 ( 34%); and older, 13,687 ( 41%). The numbers of patients in each COVID-19 wave category were as follows: Wave 1, 5372 ( 16%); Wave 2, 11,692 ( 35%); and Wave 3, 16,490 ( 49%).Figure 1The flowchart of the number of cases included in the study.Show full captionTwelve patients whose age was unknown were excluded in this analysis.Details of “ Non-fixed ” cases ( n=1,943: 5.5%) were as follows: Inclusion criteria, 446 ( 1.3%); demographics and epidemiological characteristics,740 ( 2.1%); comorbidities, 710 ( 2.0%); signs and symptoms, 1,049 ( 3.0%); outcome at discharge,1,416 ( 4.0%); supportive care, 1,368 ( 3.9%); history of drug administration, 1,315 ( 3.7%); complication during hospitalisation, 1,390 ( 3.9%) View Large Image Figure ViewerDownload Hi-res image Download ( PPT)
Twelve patients whose age was unknown were excluded in this analysis.
Details of “ Non-fixed ” cases ( n=1,943: 5.5%) were as follows:
Inclusion criteria, 446 ( 1.3%); demographics and epidemiological characteristics,740 ( 2.1%); comorbidities, 710 ( 2.0%); signs and symptoms, 1,049 ( 3.0%); outcome at discharge,1,416 ( 4.0%); supportive care, 1,368 ( 3.9%); history of drug administration, 1,315 ( 3.7%); complication during hospitalisation, 1,390 ( 3.9%)
More than half of the patients were male ( 18,985 [ 56·6% ]), and 65% of middle-aged patients were males ( Table 1). There were fewer male patients in Wave 3 than in Wave 1 or 2 ( estimated difference [ ED ] of Wave 1 vs Wave 3: 3.5% [ 1.6, 5.4 ], Wave 2 vs Wave 3: 3.1% [ 1.6, 4.5 ]) ( Table 3). Most patients ( 31,680 [ 95·5% ]) were Japanese. The median age of the entire cohort was 58 ( IQR, 39–74) years. The median age was highest in Wave 3 ( 64 [ 47–78 ]), and lowest in Wave 2 ( 50 [ 30-69 ]); ED of Wave 1 vs Wave 3: -6.0 [ -7.0, 5.0 ], Wave 2 vs Wave 3: -12.0 [ -12.0, -11.0 ]) ( Table 3). Waves 1, 2, and 3 comprised 36·3% ( 1949/5372), 30·2% ( 3532/11692), and 49·8% ( 8206/16490) of older patients, respectively.
Regarding exposure within 14 days of admission, contact with positive or probable COVID-19 patient accounted for 54·8% ( n=18,269) of cases. This was most prevalent in the under 18 group ( 914 [ 83% ]). The frequent categories of exposure were different between age groups and COVID-19 waves. Family, workplace, and healthcare facility contact were more common among patients aged < 18 years, young and middle-aged patients, and older patients, respectively. The proportion of infections from family contact increased gradually in the later waves. Young patients had the highest frequency of having meals with more than three persons or staying in crowded places. Healthcare workers constituted 5·3% ( n=1,753) of the cases. This proportion was highest during Wave 1 ( 455 [ 9·4% ]). The proportion of restaurant and nightlife business workers was highest during Wave 2.
Regarding conditions at admission, the median duration from symptom onset to hospitalisation in days was longest in the middle-aged group ( 5 [ 3, 8 ]) and during Wave 1 ( 7 [ 4, 10 ]). Young patients had least severe disease at admission ( 567 [ 7·8% ]). The incidence of severe disease at admission was lowest during Wave 2 ( 2,544 [ 21·8% ]) ( ED of Wave 1 vs Wave 2: 11.1% [ 9.3, 12.9 ], Wave 2 vs Wave 3: -10.2% [ -11.5, -9.0 ]) ( Table 3). Oxygen was administered to 13% ( n=4,312) of all patients on admission. Oxygen administration was highest among older patients ( 3,002 [ 22·1% ]).
Regarding the signs and symptoms at hospital admission, overall, 9·2% ( n=3,029) reported no symptoms. In the under 18 group, 29·2% ( n=320) were asymptomatic at hospital admission. Approximately half of the patients had a fever and cough. The frequency of some symptoms varied considerably with age. Sore throat was more common among young ( 1,763 [ 24·1% ]) and middle-aged ( 2,247 [ 19·6% ]) patients, and rhinorrhoea was more common among under 18 ( 246 [ 22·3% ]) and young ( 1,060 [ 14·5% ]) patients. Dyspnoea was most common among middle-aged patients ( 2,857 [ 25% ]). Muscle pain, headache, and diarrhoea were more common among young and middle-aged patients. Fever, cough, and fatigue were most frequent among middle-aged patients. Taste ( 2,238 [ 30·6% ]) and smell disorders ( 2,219 [ 30·4% ]) were most common among young patients.
The complication rate of any comorbidity increased with age ( Figure 2). Obesity was the most common comorbidity among young and middle-aged patients. Hypertension, obesity, and diabetes were the most common comorbidities among older patients. The frequency of any comorbidity was lowest and highest during Waves 2 and 3, respectively. In comparison of the major comorbidities between the waves, the frequency of cardiovascular disease and diabetes mellitus was highest in Wave 3, followed by Waves 1 and 2 ( ED of Wave 1 vs Wave 3: -0.9% [ -1.8, -0.1 ] for cardiovascular disease, -3.4% [ -4.8, -2.0 ] for diabetes; Wave 2 vs Wave 3: -2.4% [ -3.0, -1.8 ] for cardiovascular disease, -6.4% [ -7.5, -5.4 ] for diabetes) ( Table 3). Hypertension was most frequent in Wave 3, followed by Waves 2 and 1 ( ED of Wave 2 vs Wave 3: -12.6% [ -13.9, -11.3 ]; Wave 1 vs Wave 3: -17.3% [ -18.8, -15.7 ]). Chronic respiratory disease was less frequent in Wave 2 than in the other waves ( ED of Wave 1 vs Wave 2: 1.0% [ 0.2, 1.8 ]; Wave 2 vs Wave 3: -1.3% [ -1.8, -0.7 ]). Liver disease was more frequent in Wave 3 than Wave 2 ( ED of Wave 2 vs Wave 3: -1.3% [ -1.8, -0.7 ]. For obesity, the frequency was highest in Wave 3 and lowest in Wave 1. ( ED of Wave 1 vs Wave 3: -2.5% [ -4.5, -0.5 ]; Wave 2 vs Wave 3: -2.1% [ -3.7, -0.6 ]) Figure 2Comorbidities existing prior to COVID-19 hospitalisation.Show full captionComorbidities that existed prior to the hospitalisation for coronavirus disease ( COVID-19) were included. New-onset diseases associated with COVID-19 were excluded. The number of cases with comorbidities data were 33,554 ( obesity n=27,180). Definitions were based on Charlson scores, unless otherwise specified 27Charlson ME Pompei P Ales KL MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation.J Chronic Dis. 1987; 40: 373-383Google Scholar. Cardiovascular disease includes myocardial infarction and congestive heart failure. Chronic respiratory disease was defined as pulmonary disease in patients who were dyspnoeic with slight activity and included chronic obstructive pulmonary disease. Bronchial asthma was diagnosed based on the physician's diagnosis. Obesity was defined as a body mass index ≥ 25.View Large Image Figure ViewerDownload Hi-res image Download ( PPT)
Comorbidities that existed prior to the hospitalisation for coronavirus disease ( COVID-19) were included. New-onset diseases associated with COVID-19 were excluded. The number of cases with comorbidities data were 33,554 ( obesity n=27,180). Definitions were based on Charlson scores, unless otherwise specified 27Charlson ME Pompei P Ales KL MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation.J Chronic Dis. 1987; 40: 373-383Google Scholar. Cardiovascular disease includes myocardial infarction and congestive heart failure. Chronic respiratory disease was defined as pulmonary disease in patients who were dyspnoeic with slight activity and included chronic obstructive pulmonary disease. Bronchial asthma was diagnosed based on the physician's diagnosis. Obesity was defined as a body mass index ≥ 25.
In total, 7·2% ( n=2,409) of all patients and 10·9% ( n=1,484) of the older patients were admitted to the intensive care unit during their stays. This proportion was highest during Wave 1 ( Table 2). Overall, oxygen was not administered in 65·2% ( n=21,589) of cases; oxygen, such as nasal cannula, mask, or reservoir mask, was administered in 27·3% ( n=9,156) of cases; and high-flow oxygen therapy was used in 2·1% ( n=706) of cases. Furthermore, 4·3% ( n=1,441) and 0·4% ( n=147) of the patients were treated with IMV and ECMO, respectively. A high-flow oxygen therapy was most frequently used among older patients ( 3·7% [ 509 ]) and during Wave 3 ( 2·5% [ 415 ]). IMV and BIPAP/CPAP use were highest among older patients ( IMV: 6·8% [ 926 ], BIPAP/CPAP: 1% [ 134 ]). IMV was most frequently used during Wave 1 ( 8.2% [ 441 ]), and BIPAP/CPAP was most frequently used during Wave 2 ( 0.9% [ 103 ]). ECMO was most frequently used among middle-aged patients ( 0·8% [ 86 ]) and during Wave 1 ( 1·5% [ 83 ]). Any form oxygen use was lower in the Wave 2 than in Waves 1 and 3 ( Table 3). ( ED of Wave 1 vs Wave 2: 7.0% [ 5.5, 8.4 ]; Wave 2 vs Wave 3: -7.6% [ -8.7, -6.6 ]). The use of high-flow nasal cannula was most common in Wave 3 and least common in Wave 2 ( ED of Wave 2 vs Wave 3: -0.9% [ -1.3, -0.5 ]). BIPAP/CPAP use was more common in Wave 2 than in the other two waves ( ED of Wave 1 vs Wave 2: -0.3% [ -0.6, 0.1 ], Wave 2 vs Wave 3: 0.3% [ -0.01, 0.5 ]). IMV use was more common in Wave 1, followed by Waves 3 and 2 ( ED of Wave 1 vs Wave 3: 3.9% [ 3.0, 4.8 ], Wave 1 vs Wave 2: 4.5% [ 3.6, 5.4 ]). ECMO use was highest in Wave 1, with similar frequency in Waves 2 and 3 ( ED of Wave 1 vs Wave 3: 1.3% [ 0.9, 1.7 ], Wave 1 vs Wave 2: 1.3% [ 0.8, 1.7 ].Table 2Supportive care, outcomes, and complications during hospitalisation.Age categoryWave categoryNumber of casesSubcategoriesTotalUnder 18 ( 0–17 years) Young ( 18–39 years) Middle age ( 40–64 years) Older ( ≥65 years) Wave 1Wave 2Wave 3Supportive therapy during admissionaIf the patient received these treatments at any time during hospitalisation, the treatment was included in the analysis.Stay in ICU33,5392409 ( 7·2) 1 ( 0·1) 97 ( 1·3) 826 ( 7·2) 1484 ( 10·9) 633 ( 11·8) 709 ( 6·1) 1067 ( 6·5) Oxygen supportbIf the patient received more than one type of oxygen support during the hospitalisation, only one higher level of oxygen support was counted ( i.e. ECMO > IMV > BIPAP/CPAP > high-flow nasal canula > other oxygen support).33,545No oxygen21859 ( 65.2) 1086 ( 98.4) 6866 ( 94) 7778 ( 68) 6121 ( 44.7) 3304 ( 61.6) 8620 ( 73.7) 9935 ( 60.3) Other oxygen support ( e.g., nasal cannula, mask) 9156 ( 27.3) 18 ( 1.6) 369 ( 5.1) 2827 ( 24.7) 5939 ( 43.4) 1397 ( 26) 2385 ( 20.4) 5374 ( 32.6) High-flow nasal cannula706 ( 2.1) 0 ( 0) 16 ( 0.2) 181 ( 1.6) 509 ( 3.7) 110 ( 2) 181 ( 1.5) 415 ( 2.5) BiPAP/CPAP236 ( 0.7) 0 ( 0) 17 ( 0.2) 85 ( 0.7) 134 ( 1) 32 ( 0.6) 103 ( 0.9) 101 ( 0.6) IMV1441 ( 4.3) 0 ( 0) 30 ( 0.4) 484 ( 4.2) 926 ( 6.8) 441 ( 8.2) 371 ( 3.2) 629 ( 3.8) ECMO147 ( 0.4) 0 ( 0) 8 ( 0.1) 86 ( 0.8) 53 ( 0.4) 83 ( 1.5) 29 ( 0.2) 35 ( 0.2) Prone therapy30,294732 ( 2·4) 0 ( 0) 29 ( 0·4) 276 ( 2·7) 427 ( 3·4) 141 ( 5·5) 183 ( 1·6) 408 ( 2·5) Nitric oxide inhalation therapy30,29031 ( 0·1) 0 ( 0) 5 ( 0·1) 9 ( 0·1) 17 ( 0·1) 9 ( 0·4) 10 ( 0·1) 12 ( 0·1) Muscle relaxant30,198815 ( 2·7) 0 ( 0) 22 ( 0·3) 309 ( 3·1) 484 ( 3·9) 240 ( 9·8) 195 ( 1·7) 380 ( 2·3) Inotropic33,525837 ( 2·5) 0 ( 0) 15 ( 0·2) 238 ( 2·1) 584 ( 4·3) 270 ( 5) 206 ( 1·8) 361 ( 2·2) RRT or dialysis33,504459 ( 1·4) 0 ( 0) 6 ( 0·1) 153 ( 1·3) 300 ( 2·2) 125 ( 2·3) 112 ( 1) 222 ( 1·3) Blood transfusion33,524666 ( 2) 0 ( 0) 17 ( 0·2) 167 ( 1·5) 482 ( 3·5) 261 ( 4·9) 163 ( 1·4) 242 ( 1·5) Immunoglobulin33,518254 ( 0·8) 2 ( 0·2) 12 ( 0·2) 79 ( 0·7) 161 ( 1·2) 110 ( 2·1) 51 ( 0·4) 93 ( 0·6) Outcome at dischargeOutcome33,531Discharge24,835 ( 74·1) 1024 ( 92·8) 6293 ( 86·1) 9697 ( 84·7) 7815 ( 57·2) 3507 ( 65·3) 9450 ( 80·9) 11,878 ( 72·1) Transfer to different hospital3983 ( 11·9) 15 ( 1·4) 200 ( 2·7) 989 ( 8·6) 2777 ( 20·3) 852 ( 15·9) 1070 ( 9·2) 2061 ( 12·5) Transfer to non-medical facilitycFacilities for isolation purposes where no medical or nursing care was necessary.1656 ( 4·9) 65 ( 5·9) 801 ( 11) 593 ( 5·2) 194 ( 1·4) 500 ( 9·3) 545 ( 4·7) 611 ( 3·7) Transfer to long-term care facility1386 ( 4·1) 0 ( 0) 10 ( 0·1) 55 ( 0·5) 1321 ( 9·7) 120 ( 2·2) 290 ( 2·5) 976 ( 5·9) Dead1671 ( 5) 0 ( 0) 3 ( 0) 108 ( 0·9) 1559 ( 11·4) 391 ( 7·3) 324 ( 2·8) 956 ( 5·8) Number of deaths after oxygen supportbIf the patient received more than one type of oxygen support during the hospitalisation, only one higher level of oxygen support was counted ( i.e. ECMO > IMV > BIPAP/CPAP > high-flow nasal canula > other oxygen support).3354521,859No oxygen46 ( 0.2) 0 ( 0) 0 ( 0) 6 ( 0.1) 40 ( 0.7) 9 ( 0.3) 16 ( 0.2) 21 ( 0.2) 9156Other oxygen support ( e.g., nasal cannula, mask) 994 ( 10.9) 0 ( 0) 1 ( 0.3) 31 ( 1.1) 962 ( 16.2) 200 ( 14.3) 165 ( 6.9) 629 ( 11.7) 706High-flow nasal cannula168 ( 23.8) 0 ( 0) 0 ( 0) 8 ( 4.4) 160 ( 31.4) 22 ( 20) 38 ( 21) 108 ( 26) 236BIPAP/CPAP51 ( 21.6) 0 ( 0) 0 ( 0) 2 ( 2.4) 49 ( 36.6) 10 ( 31.2) 16 ( 15.5) 25 ( 24.8) 1441IMV369 ( 25.6) 0 ( 0) 2 ( 6.7) 44 ( 9.1) 322 ( 34.8) 127 ( 28.8) 82 ( 22.1) 160 ( 25.4) 147ECMO43 ( 29·3) 0 ( 0) 0 ( 0) 17 ( 19·8) 26 ( 49·1) 23 ( 27·7) 7 ( 24·1) 13 ( 37·1) TracheotomydData were counted only for the patients who were discharged alive.31,808241 ( 0·8) 1 ( 0·1) 18 ( 0·2) 86 ( 0·8) 136 ( 1·1) 76 ( 1·5) 70 ( 0·6) 95 ( 0·6) Worsened self-care abilitydData were counted only for the patients who were discharged alive.31,2912667 ( 8·5) 1 ( 0·1) 49 ( 0·7) 628 ( 5·6) 1989 ( 16·9) 514 ( 10·7) 681 ( 6·1) 1472 ( 9·6) Worsened walking abilitydData were counted only for the patients who were discharged alive.30,5622716 ( 8·9) 1 ( 0·1) 52 ( 0·7) 637 ( 5·9) 2026 ( 17·5) 492 ( 11·9) 723 ( 6·4) 1501 ( 9·9) O2 administration at dischargedData were counted only for the patients who were discharged alive.31,8222128 ( 6·7) 3 ( 0·3) 58 ( 0·8) 673 ( 5·9) 1394 ( 11·5) 370 ( 7·5) 572 ( 5) 1186 ( 7·6) Complications during admissionBacterial pneumoniae ( incl. HAP/VAP) 33,4971791 ( 5·3) 3 ( 0·3) 39 ( 0·5) 319 ( 2·8) 1429 ( 10·5) 411 ( 7·7) 467 ( 4) 913 ( 5·5) ARDS33,4941501 ( 4·5) 0 ( 0) 31 ( 0·4) 457 ( 4) 1013 ( 7·4) 484 ( 9) 341 ( 2·9) 676 ( 4·1) Severity of ARDS1452Mild278 ( 19·1) 0 ( 0) 8 ( 26·7) 115 ( 25·8) 155 ( 15·9) 52 ( 11·7) 61 ( 18·3) 165 ( 24·6) Moderate482 ( 33·2) 0 ( 0) 11 ( 36·7) 177 ( 39·7) 294 ( 30·1) 147 ( 33) 133 ( 39·8) 202 ( 30·1) Severe692 ( 47·7) 0 ( 0) 11 ( 36·7) 154 ( 34·5) 527 ( 54) 247 ( 55·4) 140 ( 41·9) 305 ( 45·4) Pneumothorax33,489142 ( 0·4) 0 ( 0) 6 ( 0·1) 25 ( 0·2) 111 ( 0·8) 48 ( 0·9) 34 ( 0·3) 60 ( 0·4) Pleural fluid33,488994 ( 3) 0 ( 0) 17 ( 0·2) 176 ( 1·5) 801 ( 5·9) 277 ( 5·2) 230 ( 2) 487 ( 3) Meningitis33,48822 ( 0·1) 0 ( 0) 4 ( 0·1) 9 ( 0·1) 9 ( 0·1) 12 ( 0·2) 3 ( 0) 7 ( 0) Seizure33,48780 ( 0·2) 3 ( 0·3) 6 ( 0·1) 24 ( 0·2) 47 ( 0·3) 29 ( 0·5) 23 ( 0·2) 28 ( 0·2) Stroke33,496125 ( 0·4) 0 ( 0) 2 ( 0) 25 ( 0·2) 98 ( 0·7) 39 ( 0·7) 33 ( 0·3) 53 ( 0·3) Deep vein thrombosis32,828215 ( 0·7) 0 ( 0) 6 ( 0·1) 51 ( 0·5) 158 ( 1·2) 53 ( 1·1) 60 ( 0·5) 102 ( 0·6) Myocarditis33,48731 ( 0·1) 1 ( 0·1) 3 ( 0) 12 ( 0·1) 15 ( 0·1) 14 ( 0·3) 5 ( 0) 12 ( 0·1) Arrythmia33,482159 ( 0·5) 1 ( 0·1) 5 ( 0·1) 30 ( 0·3) 123 ( 0·9) 47 ( 0·9) 45 ( 0·4) 67 ( 0·4) Cardiac ischemia33,48756 ( 0·2) 0 ( 0) 1 ( 0) 13 ( 0·1) 42 ( 0·3) 15 ( 0·3) 20 ( 0·2) 21 ( 0·1) Bacteraemia33,488291 ( 0·9) 2 ( 0·2) 5 ( 0·1) 72 ( 0·6) 212 ( 1·6) 80 ( 1·5) 88 ( 0·8) 123 ( 0·7) Gastrointestinal bleeding33,469188 ( 0·6) 0 ( 0) 7 ( 0·1) 30 ( 0·3) 151 ( 1·1) 52 ( 1) 52 ( 0·4) 84 ( 0·5) Clostridium difficile infection33,47369 ( 0·2) 0 ( 0) 3 ( 0) 11 ( 0·1) 55 ( 0·4) 17 ( 0·3) 29 ( 0·2) 23 ( 0·1) Pulmonary thromboembolism32,81177 ( 0·2) 0 ( 0) 7 ( 0·1) 21 ( 0·2) 49 ( 0·4) 27 ( 0·6) 12 ( 0·1) 38 ( 0·2) Data are presented as n (%) unless otherwise indicated.As the number of missing values differed for each parameter, the number of cases in each parameter's age/wave category was used as the denominator for calculating the percentage.Abbreviations: BiPAP/CPAP, bilevel positive airway pressure/continuous positive airway pressure; ECMO, extracorporeal membrane oxygenation; HAP/VAP, hospital-acquired pneumonia/ventilator-associated pneumonia. IMV, invasive mechanical ventilation; IQR, interquartile range; RRT, renal replacement therapy; a If the patient received these treatments at any time during hospitalisation, the treatment was included in the analysis.b If the patient received more than one type of oxygen support during the hospitalisation, only one higher level of oxygen support was counted ( i.e. ECMO > IMV > BIPAP/CPAP > high-flow nasal canula > other oxygen support).c Facilities for isolation purposes where no medical or nursing care was necessary.d Data were counted only for the patients who were discharged alive. Open table in a new tab Table 3Comparison of the major characteristics, drug administration, and oxygen support during hospitalisation among each wave.VariableWave 1Wave 2Wave 3Wave 1 vs Wave 2Wave 1 vs Wave 3Wave 2 vs Wave 3Number (%) Estimated difference * [ confidence interval† ] P value‡Bonferroni correction was used for pairwise comparisons among waves ( threshold of significant difference was 0.0167). Statistically significant values are shown in bold. Abbreviations. BiPAP/CPAP, bilevel positive airway pressure/continuous positive airway pressure; BMI, body mass index; ECMO, extracorporeal membrane oxygenation; IMV, invasive mechanical ventilation; IQR, interquartile range. A Cardiovascular disease includes myocardial infarction/Congestive heart failure. Chronic respiratory disease was defined as pulmonary disease in patients who were dyspneic with slight activity and included chronic obstructive pulmonary disease. B Any form of oxygen support includes high-flow nasal canula, non-IMV, IMV, ECMO, and other oxygen support ( e.g. nasal cannula, mask).Estimated difference * [ confidence interval† ] P value‡Bonferroni correction was used for pairwise comparisons among waves ( threshold of significant difference was 0.0167). Statistically significant values are shown in bold. Abbreviations. BiPAP/CPAP, bilevel positive airway pressure/continuous positive airway pressure; BMI, body mass index; ECMO, extracorporeal membrane oxygenation; IMV, invasive mechanical ventilation; IQR, interquartile range. A Cardiovascular disease includes myocardial infarction/Congestive heart failure. Chronic respiratory disease was defined as pulmonary disease in patients who were dyspneic with slight activity and included chronic obstructive pulmonary disease. B Any form of oxygen support includes high-flow nasal canula, non-IMV, IMV, ECMO, and other oxygen support ( e.g. nasal cannula, mask).Estimated difference * Earlier wave was used as reference. †98.33% confidence intervals were calculated because significance threshold was corrected by Bonferroni method. [ confidence interval† ] P value‡Bonferroni correction was used for pairwise comparisons among waves ( threshold of significant difference was 0.0167). Statistically significant values are shown in bold. Abbreviations. BiPAP/CPAP, bilevel positive airway pressure/continuous positive airway pressure; BMI, body mass index; ECMO, extracorporeal membrane oxygenation; IMV, invasive mechanical ventilation; IQR, interquartile range. A Cardiovascular disease includes myocardial infarction/Congestive heart failure. Chronic respiratory disease was defined as pulmonary disease in patients who were dyspneic with slight activity and included chronic obstructive pulmonary disease. B Any form of oxygen support includes high-flow nasal canula, non-IMV, IMV, ECMO, and other oxygen support ( e.g. nasal cannula, mask).Patient demographics and characteristics on admissionAge, median [ IQR ], years56 [ 40, 71 ] 50 [ 30, 69 ] 64 [ 47, 78 ] 6.0 [ 5.0, 7.0 ] < 0.001-6.0 [ -7.0, -5.0 ] < 0.001-12.0 [ -12.0, -11.0 ] < 0.001Male sex3139 ( 58.5) 6784 ( 58) 9062 ( 55) 0.004 [ -0.015, 0.024 ] 0.5980.035 [ 0.016, 0.054 ] < 0.0010.031 [ 0.016, 0.045 ] < 0.001Severe disease at admission1767 ( 32.9) 2544 ( 21.8) 5276 ( 32) 0.111 [ 0.093, 0.129 ] < 0.0010.009 [ -0.009, 0.027 ] 0.228-0.102 [ -0.115, -0.090 ] < 0.001ComorbiditiesACardiovascular disease268 ( 5) 408 ( 3.5) 973 ( 5.9) 0.015 [ 0.007, 0.023 ] < 0.001-0.009 [ -0.018, -0.001 ] 0.001-0.024 [ -0.030, -0.018 ] < 0.001Chronic respiratory disease109 ( 2) 133 ( 1.1) 263 ( 1.6) 0.010 [ 0.002, 0.018 ] 0.001-0.003 [ -0.010, 0.005 ] 0.381-0.013 [ -0.018, -0.007 ] < 0.001Liver disease130 ( 2.4) 235 ( 2) 422 ( 2.6) 0.004 [ -0.002, 0.010 ] 0.096-0.001 [ -0.007, 0.005 ] 0.607-0.005 [ -0.010, -0.001 ] 0.003Diabetes Mellitus856 ( 15.9) 1509 ( 12.9) 3191 ( 19.4) 0.030 [ 0.016, 0.044 ] < 0.001-0.034 [ -0.048, -0.020 ] < 0.001-0.064 [ -0.075, -0.054 ] < 0.001Cerebrovascular disease337 ( 6.3) 552 ( 4.7) 1342 ( 8.1) 0.016 [ 0.006, 0.025 ] < 0.001-0.019 [ -0.028, -0.009 ] < 0.001-0.034 [ -0.041, -0.027 ] < 0.001Hypertension1050 ( 19.5) 2831 ( 24.2) 6068 ( 36.8) -0.047 [ -0.063, -0.030 ] < 0.001-0.173 [ -0.188, -0.157 ] < 0.001-0.126 [ -0.139, -0.113 ] < 0.001BMI > =251366 ( 32.8) 3171 ( 33.2) 4762 ( 35.4) -0.004 [ -0.025, 0.017 ] 0.688-0.025 [ -0.045, -0.005 ] < 0.003-0.021 [ -0.037, -0.006 ] 0.001Drug administrationSteroid ( excl. ciclesonide) 497 ( 9.4) 2384 ( 20.4) 6569 ( 39.9) -0.110 [ -0.124, -0.097 ] < 0.001-0.305 [ -0.318, -0.292 ] < 0.001-0.195 [ -0.207, -0.182 ] < 0.001Tocilizumab66 ( 2.6) 259 ( 5.6) 393 ( 4.7) -0.030 [ -0.041, -0.019 ] < 0.001-0.022 [ -0.032, -0.012 ] < 0.0010.008 [ -0.002, 0.018 ] 0.051Remdesivir2 ( 0.9) 1074 ( 23.2) 2682 ( 32.4) -0.223 [ -0.239, -0.208 ] < 0.001-0.315 [ -0.329, -0.302 ] < 0.001-0.092 [ -0.112, -0.073 ] < 0.001Favipiravir2037 ( 69.5) 2664 ( 57.4) 4415 ( 53.3) 0.122 [ 0.095, 0.149 ] < 0.0010.164 [ 0.139, 0.188 ] < 0.0010.042 [ 0.020, 0.064 < 0.001Anticoagulant538 ( 10.0) 1416 ( 12.1) 3674 ( 22.3) -0.021 [ -0.034, -0.009 ] < 0.001-0.123 [ -0.136, -0.111 ] < 0.001-0.102 [ -0.113, -0.091 ] < 0.001Oxygen supportAny formB2063 ( 38.4) 3069 ( 26.3) 6554 ( 39.7) 0.070 [ 0.055, 0.084 ] < 0.001-0.007 [ -0.021, 0.007 ] 0.254-0.076 [ -0.087, -0.066 ] < 0.001High-flow nasal canula110 ( 2.0) 181 ( 1.5) 415 ( 2.5) 0.005 [ -0.001, 0.010 ] 0.025-0.004 [ -0.010, 0.001 ] 0.064-0.009 [ -0.013, -0.005 ] < 0.001BiPAP/CPAP32 ( 0.6) 103 ( 0.9) 101 ( 0.6) -0.003 [ -0.006, 0.001 ] 0.065-0.0002 [ -0.003, 0.003 ] 0.9720.003 [ -0.0001, 0.005 ] 0.011IMV441 ( 8.2) 371 ( 3.2) 629 ( 3.8) 0.045 [ 0.036, 0.054 ] < 0.0010.039 [ 0.030, 0.048 ] < 0.001-0.006 [ -0.011, -0.001 ] 0.006ECMO83 ( 1.5) 29 ( 0.2) 35 ( 0.2) 0.013 [ 0.008, 0.017 ] < 0.0010.013 [ 0.009, 0.017 ] < 0.0010.0004 [ -0.001, 0.002 ] 0.622 Earlier wave was used as reference.†98.33% confidence intervals were calculated because significance threshold was corrected by Bonferroni method.‡ Bonferroni correction was used for pairwise comparisons among waves ( threshold of significant difference was 0.0167). Statistically significant values are shown in bold.Abbreviations. BiPAP/CPAP, bilevel positive airway pressure/continuous positive airway pressure; BMI, body mass index; ECMO, extracorporeal membrane oxygenation; IMV, invasive mechanical ventilation; IQR, interquartile range.A Cardiovascular disease includes myocardial infarction/Congestive heart failure. Chronic respiratory disease was defined as pulmonary disease in patients who were dyspneic with slight activity and included chronic obstructive pulmonary disease.B Any form of oxygen support includes high-flow nasal canula, non-IMV, IMV, ECMO, and other oxygen support ( e.g. nasal cannula, mask). Open table in a new tab
Data are presented as n (%) unless otherwise indicated.
As the number of missing values differed for each parameter, the number of cases in each parameter's age/wave category was used as the denominator for calculating the percentage.
Abbreviations: BiPAP/CPAP, bilevel positive airway pressure/continuous positive airway pressure; ECMO, extracorporeal membrane oxygenation; HAP/VAP, hospital-acquired pneumonia/ventilator-associated pneumonia. IMV, invasive mechanical ventilation; IQR, interquartile range; RRT, renal replacement therapy;
Overall, 74·1% ( n=24,835) of patients were discharged home from the hospitals, 11·9% ( n=3,983) were transferred to a different hospital, 4·9% ( n=1,656) were transferred to a non-medical facility such as hotels, 4·1% ( n=1,386) were transferred to a long-term care facility, and 5% ( n=1,671) died. The proportion of deaths increased dramatically among older patients ( 11·4% [ 1,559 ]).
Case fatality rate was highest and lowest during Wave 1 ( 7·3% [ 391 ]) and 2 ( 2·8% [ 324 ]), respectively. Case fatality rate was highest among patients who received ECMO ( 29·3% [ 43 ]), followed by those who received IMV ( 25·6% [ 369 ]), high-flow oxygen therapy ( 23·8% [ 168 ]), and BIPAP/CPAP ( 21·6% [ 51 ]). Most deaths were among older patients ( 93·3%, n = 1559/1671). In the old group, more than one-third of the patients who were treated with IMV, and about half of the patients who were treated with ECMO, died. Among the older patients, approximately 17% ( n=1,989) experienced worsened self-care/walking ability and 11·5% ( n=1,394) required oxygen upon discharge.
Bacterial pneumonia was the most common complication ( 5.3% [ 1,791 ]), followed by acute respiratory distress syndrome ( ARDS) ( 4·5% [ 1,501 ]). Deep vein thrombosis and pulmonary embolism were diagnosed in 0·7% ( n=215) and 0·2% ( n=77) of the patients, respectively.
The severity of disease ( indicated by respiratory supports during hospitalisation) and deaths among middle-aged and older patients are shown in Figure 3, and related values are presented in Supplementary Table 2. Among middle-aged patients, IMV and/or ECMO were used more frequently during Wave 1 ( 10.5% [ 225 ]) than during waves 2 ( 3.7% [ 147 ]) and 3 ( 3.7% [ 198 ]), and death was most prominent during Wave 1 ( 12% [ 27 ]) followed by Wave 3 ( 11.1% [ 22 ]) and Wave 2 ( 8.2% [ 12 ]) among patients who were treated with IMV and/or ECMO. Among older patients, the use of IMV and/or ECMO in both survivors and those who died was less frequent during Wave 3 ( survivors: 4.2% [ 308 ], non-survivor: 16.5% [ 150 ], respectively) than during Wave 1 ( 9.9% [ 157 ] and 34.6% [ 121 ], respectively).Figure 3Epidemiologic curve of severity and death in middle-aged and older patients.Show full caption ( a) and ( b) show the number of patients in each category in the middle and old age groups, respectively. The upward graphs ( discharged/transferred) show the patients who were alive at the time of discharge, and the downward graphs ( deaths) show the patients who died during hospitalisation. “ Transferred ” included patients who were transferred to either different hospital, non-medical facility, or long-term care facility. The outcome of patients who were transferred from the hospitals participating in the study at the time of admission are summarised in Supplementary Table 3. Detailed numbers in the figure are presented in Supplementary Table 2.No oxygen: patients who were never supported with supplemental oxygen during hospitalisation.Oxygen: patients who were supported with non-IMV or supplemental oxygen ( including high-flow oxygen devices) during hospitalisation.IMV/ECMO: Patients who were supported with invasive mechanical ventilation ( IMV) or extracorporeal membrane oxygenation ( ECMO).View Large Image Figure ViewerDownload Hi-res image Download ( PPT)
( a) and ( b) show the number of patients in each category in the middle and old age groups, respectively. The upward graphs ( discharged/transferred) show the patients who were alive at the time of discharge, and the downward graphs ( deaths) show the patients who died during hospitalisation. “ Transferred ” included patients who were transferred to either different hospital, non-medical facility, or long-term care facility. The outcome of patients who were transferred from the hospitals participating in the study at the time of admission are summarised in Supplementary Table 3. Detailed numbers in the figure are presented in Supplementary Table 2.
No oxygen: patients who were never supported with supplemental oxygen during hospitalisation.
Oxygen: patients who were supported with non-IMV or supplemental oxygen ( including high-flow oxygen devices) during hospitalisation.
IMV/ECMO: Patients who were supported with invasive mechanical ventilation ( IMV) or extracorporeal membrane oxygenation ( ECMO).
Use of steroids ( excluding ciclesonide), remdesivir, and anticoagulants increased over time ( ED of steroid: Wave 1 vs Wave 2: -11.0% [ -12.4, -9.7 ], Wave 2 vs Wave 3: -19.5% [ -20.7, -18.2 ]; remdesivir: Wave 1 vs Wave 2: -22.3% [ -23.9, -20.8 ], Wave 2 vs Wave 3: -9.2% [ -11.2, -7.3 ]; anticoagulant: Wave 1 vs Wave 2: -2.1% [ -3.4, -0.9 ], Wave 2 vs Wave 3: -10.2% [ -11.3, -9.1 ]) ( Figure 4) ( Table 3). In contrast, ciclesonide, favipiravir, and nafamostat use decreased over time. Tocilizumab use was most frequent in Wave 2, followed by Waves 3 and 1 ( ED of Wave 2 vs Wave 3: 0.8% [ -0.2, 1.8 ], Wave 1 vs Wave 2: -3.0% [ -4.1, -1.9 ]). The use of most medications, except for favipiravir and ciclesonide, increased with age. Baricitinib was not administered to this cohort. Antimicrobials were administered in 23·3% ( n=7,800) ( under 18, 4·1% [ 45 ]; young, 7% [ 507 ]; middle age, 19·4% [ 2,211 ]; older patients, 36·9% [ 5,036 ]; Wave 1, 35·9% [ 1,916 ]; Wave 2, 18% [ 2,108 ]; and Wave 3, 22·9% [ 3,776 ]), and antifungal drugs in 0·9% ( n=309) ( under 18, 0% [ 0 ]; young, 0·2% [ 14 ]; middle age, 0·7% [ 81 ]; older patients, 1·6% [ 214 ]; Wave 1, 1·9% [ 101 ]; Wave 2, 0·7% [ 83 ]; and Wave 3, 0·8% [ 125 ]) of the cases.Figure 4History of drug administration during hospitalisation.Show full captionMedications with antiviral effects against severe acute respiratory syndrome coronavirus 2, immunomodulatory effects against coronavirus disease ( COVID-19), and/or immunosuppressive effects against COVID-19 were included. Ciclesonide is available only as an inhalant. Steroids ( other than ciclesonide) were administered in 9,450 cases. For oral, intravenous, and inhalation administration, there were 5,279, 5,086, and 86 cases, respectively. There were 9,376 cases of either oral or intravenous administration. If more than one preparation was used for one patient, each was counted. Anticoagulation therapy included unfractionated heparin, low-molecular-weight heparin, fondaparinux, and oral anticoagulants ( warfarin and direct oral anticoagulants: dabigatran, rivaroxaban, apixaban, and edoxaban) during hospitalisation. In this study, we did not distinguish between prophylactic and therapeutic administration of thromboembolism. We did not count concomitant therapies in the present analysis. The denominator is not the total number of patients, but the number of patients who were administered any drug to treat COVID-19 ( n=15,880) for whom the data of each antiviral drug was not missing. For example, the proportion of patients administered favipiravir was calculated as: with favipiravir/ ( with favipiravir + without favipiravir).View Large Image Figure ViewerDownload Hi-res image Download ( PPT)
Medications with antiviral effects against severe acute respiratory syndrome coronavirus 2, immunomodulatory effects against coronavirus disease ( COVID-19), and/or immunosuppressive effects against COVID-19 were included. Ciclesonide is available only as an inhalant. Steroids ( other than ciclesonide) were administered in 9,450 cases. For oral, intravenous, and inhalation administration, there were 5,279, 5,086, and 86 cases, respectively. There were 9,376 cases of either oral or intravenous administration. If more than one preparation was used for one patient, each was counted. Anticoagulation therapy included unfractionated heparin, low-molecular-weight heparin, fondaparinux, and oral anticoagulants ( warfarin and direct oral anticoagulants: dabigatran, rivaroxaban, apixaban, and edoxaban) during hospitalisation. In this study, we did not distinguish between prophylactic and therapeutic administration of thromboembolism. We did not count concomitant therapies in the present analysis. The denominator is not the total number of patients, but the number of patients who were administered any drug to treat COVID-19 ( n=15,880) for whom the data of each antiviral drug was not missing. For example, the proportion of patients administered favipiravir was calculated as: with favipiravir/ ( with favipiravir + without favipiravir).
A total of 1,306 patients were transferred from the institutions participating in the study at the time of admission. As for patients ' demographics and characteristics on admission ( Supplementary Table 3), compared to the whole cohort, there were more male patients ( 69.2% [ n=904 ] vs 56.6% [ 18,985 ]) and more patients in Wave 1 ( 24.7% [ 322 ] vs 16% [ 5,372 ]) in the transferred cohort. There was also a higher median BMI ( 24.2 vs 23.3), a higher rate of immunodeficiency ( 4.2% [ 54 ] vs 2.2% [ 708 ]), and higher rate of severe disease on admission ( 68.5% [ 894 ] vs. 28.6% [ 9,587 ]) in the transferred cohort than in the whole cohort. The prevalence of any comorbidity was higher in transferred patients than the whole cohort ( 78.1% [ 1,020 ] vs 54.5% [ 18,295 ]), and for all individual comorbidities except leukaemia/lymphoma, the prevalence was higher in transferred patients. Regarding supportive care, outcome, and complications during hospitalisation, transferred patients had more ICU stays than the whole cohort ( 35.2% [ 458 ] vs. 7.2% [ 2,409 ]), and were more often treated by IMV ( 23.9% [ 312 ] vs 4.7%) and ECMO ( 3.4% [ 45 ] vs 0.4% [ 147 ]). In terms of the outcomes, discharge home was less common ( 51.4% [ 671 ] vs. 74.1% [ 24,835 ]) and death ( 11.9% [ 155 ] vs 5% [ 1,671 ]) was more common in the transferred cohort than in the whole cohort. Steroids, anticoagulants, remdesivir, tocilizumab, and nafamostat tended to be administered more frequently in transferred patients than in the whole cohort. In Waves 2 and 3, ciclesonide and favipiravir tended to be administered less frequently in the transferred cohort than in the whole cohort.
After adjusting for other parameters that could interact with the risk of death and the transfer status on admission, compared to Wave 1, Wave 2 and Wave 3 rather decreased the risk of death ( Table 4). The analysis was performed excluding patients transferred on admission ( Supplementary Table 4-a). In this analysis, the trend of the results did not change from the analysis results that included transferred patients. The number of facilities that continuously participated in COVIREGI-JP from Wave 1 to Wave 3 was 234 ( 42.3% of 553 facilities). For each wave, 234 facilities accounted for about 60% of the total number of facilities ( Wave 1: 234/378 [ 61.9% ], Wave 2: 234/412 [ 56.8% ], Wave 3: 234/408 [ 57.4% ]). The number of patients ( n=24806) from 234 institutions that had continuously participated in COVIREGI-JP accounted for 73.9% of the total patients ( n=33554), and about 70% of the total for each wave ( Wave 1: 3579/5372 [ 66.6% ], Wave 2: 8771/11692 [ 75% ], Wave 3: 12456/16490 [ 75.5% ]). We performed the analysis to evaluate the effect of each wave on death, including only the patients from the facilities that continued to participate over three waves ( Supplementary Table 4-b and 4-c). The results of the effect of each wave on death were similar to that of total participating facilities.Table 4Evaluation of the effect of each wave on death during hospitalization.Risk ratio95% CIP valueParametersUnivariableMultivariableUnivariableMultivariableUnivariableMultivariableEffect of each waveWave 1ReferenceWave 20.3630.398 [ 0.312-0.423 ] [ 0.40-0.561 ] < 0.001 < 0.001Wave 30.7830.473 [ 0.694-0.886 ] [ 0.325-0.487 ] < 0.001 < 0.001Other risk factorsTransfer from other facilities3.9161.629 [ 3.479-4.401 ] [ 1.390-1.906 ] < 0.001 < 0.001Age1.0921.103 [ 1.088-1.097 ] [ 1.096-1.110 ] < 0.001 < 0.001Male sex1.3221.872 [ 1.195-1.464 ] [ 1.621-2.165 ] < 0.001 < 0.001Obesity ( BMI > =25) 0.6781.098 [ 0.593-0.773 ] [ 0.940-1.281 ] < 0.0010.236Cardiovascular and peripheral vascular diseaseA4.9891.521 [ 4.394-5.654 ] [ 1.277-1.805 ] < 0.001 < 0.001Chronic Respiratory DiseaseB4.7281.675 [ 4.055-5.492 ] [ 1.367-2.043 ] < 0.001 < 0.001Liver disease2.2812.459 [ 1.793-2.865 ] [ 1.780-3.347 ] < 0.001 < 0.001Diabetes mellitus2.3771.388 [ 2.132-2.647 ] [ 1.199-1.605 ] < 0.001 < 0.001Cerebrovascular Disease3.9651.370 [ 3.482-4.504 ] [ 1.455-1.632 ] < 0.001 < 0.001Hypertension2.2910.790 [ 2.075-2.530 ] [ 0.688-0.906 ] < 0.001 < 0.001Severe condition at admission6.7663.026 [ 6.075-7.546 ] [ 2.624-3.493 ] < 0.001 < 0.001Abbreviations. BMI, body mass index; CI, confidence interval. A Cardiovascular and peripheral vascular disease includes myocardial infarction, congestive heart failure, and peripheral vascular disease. B Chronic respiratory disease was defined as pulmonary disease in patients who were dyspneic with slight activity and included chronic obstructive pulmonary disease. Open table in a new tab
Abbreviations. BMI, body mass index; CI, confidence interval. A Cardiovascular and peripheral vascular disease includes myocardial infarction, congestive heart failure, and peripheral vascular disease. B Chronic respiratory disease was defined as pulmonary disease in patients who were dyspneic with slight activity and included chronic obstructive pulmonary disease.
We analysed a large cohort of mostly unvaccinated hospitalised Japanese patients with COVID-19. Our cohort included approximately 7% ( n=33,554) of the total number of reported COVID-19 cases in Japan as of the end of March 2021 ( n=469,713).14Ministry of Health, Labour and Welfare. Current status of the novel coronavirus infection and the response of the MHLW. March 31,2021 Available at: https: //www.mhlw.go.jp/stf/newpage 17801.html. Accessed 10 December 2021.Google Scholar A comparison of cases from Japan, with that from Western countries, and other Asian countries, based on available data by the end of March 2021, shows that the cumulative deaths per million people are lower in Japan than in Western countries, but higher than those of most Asian countries ( e.g., Japan, 72·8; US, 1656·4; Germany, 912·9; United Kingdom, 1861·3; China 3·21; Singapore, 5·5; South Korea, 33.8; Philippines, 119.7).15Ritchie H, Mathieu E, Rodés-Guirao L, et al. Coronavirus ( COVID-19) Deaths. Published online at OurWorldInData.org. 2020. Retrieved from: https: //ourworldindata.org/covid-deaths. Accessed 10 December 2021.Google Scholar In comparison with Western countries, the case fatality rate for Japan ( 1.9) was similar to that of the U.S. ( 1.8), and lower than that for other countries ( Germany, 2.7; United Kingdom, 2.9).15Ritchie H, Mathieu E, Rodés-Guirao L, et al. Coronavirus ( COVID-19) Deaths. Published online at OurWorldInData.org. 2020. Retrieved from: https: //ourworldindata.org/covid-deaths. Accessed 10 December 2021.Google Scholar In comparison with Asian countries, the case fatality rate for Japan was lower than that for China ( 5.1) but higher than that for Singapore ( 0.05), and similar to that for other countries ( South Korea, 1.7; Philippines, 1.8).15Ritchie H, Mathieu E, Rodés-Guirao L, et al. Coronavirus ( COVID-19) Deaths. Published online at OurWorldInData.org. 2020. Retrieved from: https: //ourworldindata.org/covid-deaths. Accessed 10 December 2021.Google Scholar The proportion of people vaccinated against COVID-19 where data are available by the end of March 2021, are 0·1%, 0·05%, 5%, 6·6%, and 19% in Japan, Korea, Germany, the UK, and the US, respectively.5Ritchie H, Mathieu E, Rodés-Guirao L,, et al. Coronavirus Pandemic ( COVID-19) – Japan: Coronavirus ( COVID-19) Vaccinations. Published online at OurWorldInData.org. 2020. Retrieved from: https: //ourworldindata.org/covid-vaccinations? country=∼JPN. Accessed 10 December 2021.Google Scholar Considering the lower proportion of people vaccinated in Japan by the end of March 2021 than Western countries, the case fatality rate among unvaccinated people in Japan was likely to be lower than those in Western countries. The case fatality rate in the inpatient cohort of 7·3% in Wave 1 in this report is lower than the case fatality rate ( of over 15%) in China, the UK, and the US at the beginning of the epidemic.16Docherty AB Harrison EM Green CA et al.Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study.BMJ. 2020; 369: m1985Google Scholar, 17Richardson S Hirsch JS Narasimhan M et al.Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area.JAMA. 2020; 323: 2052-2059Google Scholar, 18Zhou F Yu T Du R et al.Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.Lancet. 2020; 395: 1054-1062Google Scholar It is also lower than the 12% in the Philippines at the start of the epidemic19Agrupis KA Smith C Suzuki S et al.Epidemiological and clinical characteristics of the first 500 confirmed COVID-19 inpatients in a tertiary infectious disease referral hospital in Manila, Philippines.Trop Med Health. 2021; 49: 48Google Scholar; however, it is higher than the 0.9% in Singapore.20Tan JB Cook MJ Logan P Rozanova L Wilder-Smith A. Singapore's Pandemic Preparedness: An Overview of the First Wave of COVID-19.Int J Environ Res Public Health. 2020; 18: 252Google Scholar However, simple comparisons are difficult due to factors such as different times of infection, hospitalisation recommendation ( i.e., denominator as hospitalised patients), effects of age and comorbidities, and medical resources. As previously discussed,2Matsunaga N Hayakawa K Terada M et al.Clinical epidemiology of hospitalized patients with COVID-19 in Japan: report of the COVID-19 REGISTRY JAPAN.Clin Infect Dis. 2020; Google Scholar despite the relatively high number of older patients, Japan has a low case fatality rate. This may be related to the low frequency of comorbidities, such as diabetes, obesity, and cardiovascular diseases. Moreover, the total number of cases did not surge to the point of causing a complete healthcare system meltdown. In addition, the present cohort included many patients with relatively mild disease due to the hospitalisation recommendation in Japan ( Supplementary Table 5). For example, in a US cohort of 192,550 inpatients ( with a case fatality rate of 13·6%) between March and August 2020, 28·9% ( n=55,593) were admitted to ICU,21Nguyen NT Chinn J Nahmias J et al.Outcomes and mortality among adults hospitalized with COVID-19 at US medical centers.JAMA Netw Open. 2021; 4e210417https: //doi.org/10.1001/jamanetworkopen.2021.0417Google Scholar compared to 7·2% ( n=2,409) in this cohort. Furthermore, in a UK cohort of 20,133 inpatients between 6 February and 19 April 2020, 17% ( n=3,001/18,183) were admitted to ICU and 10% ( 1,658/16,866) received IMV,16Docherty AB Harrison EM Green CA et al.Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study.BMJ. 2020; 369: m1985Google Scholar while in this cohort only 4·3% ( n=1,441) received IMV.
Age group comparisons revealed differences in epidemiologic characteristics. This indicates the need for tailored infection prevention and treatment approaches for each age group. The young patients tended to have a history of close contact with COVID-19 cases in the workplace. Furthermore, they engaged in high-risk behaviour, such as having meals with multiple non-family members or staying in crowded places. For the older patients, exposure to COVID-19 was mostly in the healthcare facility and at home.
Our previous analysis included 2,638 patients mainly from Wave 1, and the case fatality rate was as high as 7·5% ( n=197).2Matsunaga N Hayakawa K Terada M et al.Clinical epidemiology of hospitalized patients with COVID-19 in Japan: report of the COVID-19 REGISTRY JAPAN.Clin Infect Dis. 2020; Google Scholar In the current cohort, more patients ( n=5,372) were included from Wave 1. The resulting Wave 1 case fatality rate was 7·3% ( n=391), which was slightly lower than the previously reported case fatality rate. Wave comparison revealed that each wave had different characteristics: Wave 1 had severe disease and the worst case fatality rate; Wave 2 had young patients and mild disease; and Wave 3 had older patients with comorbidities. The differences that were considered clinically significant were age ( 12 for ED of Waves 2 vs Wave 3), the severity of illness at admission ( ED in Wave 2 were about 10% lower than those in Waves 1 and Wave 3), and hypertension ( ED in Wave 2 were more than 10% lower than those in Waves 3 and 1). Other comorbidities also had lower EDs, especially in Wave 2, by more than a few percent than in Wave 3. In the multivariable analysis using a relative risk regression model in which the effects of other factors such as age and comorbidities were controlled, Wave 2 and Wave 3 had less risk of death than Wave 1. The median duration from symptom onset to hospitalisation was shortened from seven days during Wave 1 to four days during Wave 3. Furthermore, Wave 3 comprised a smaller percentage of patients who were on invasive or non-IMV or on ECMO at admission ( Wave 1: 2·7% [ 143 ] vs Wave 3: 1·1% [ 174 ]).
Besides the opportunity of being admitted to hospital before the disease became severe, there were also differences in post-hospitalisation treatment between epidemic waves. The use of steroids was about four times more frequent during Wave 3 than during Wave 1, and the use of anticoagulants more than doubled. For steroids and remdesivir, ED increased by about 30% in the comparison between Waves 1 and Wave 3. Anticoagulants also showed a large difference in ED in Wave 2 and Wave 3, with an increase of ED about 10%.In terms of supportive care, the use of invasive supportive care, such as IMV and ECMO was lower during Wave 3 than during Wave 1, with ED of 3.9% for IMV and 1.3% for ECMO. Deaths following the use of high-flow therapy were most prominent during Wave 3 among the three epidemic waves.
Invasive supportive care may have been more reserved during Wave 3 than during Wave 1 due to various factors, such as the higher proportion of older patients during Wave 3; the increased number of COVID-19 patients, which strained medical institutions, compared to Wave 1; improved understanding of the disease; and the avoidance of invasive ventilator-associated complications through the use of high-flow oxygen therapy. Besides these factors, the fact that case fatality rate during Wave 3 was lower than that during Wave 1, despite the increase in age and comorbidity, may indicate an improvement in prognosis over time. This is also supported by the multivariable analysis results which adjusted for the confounding effects of age and comorbidity. Similar improvements in prognosis over the pandemic period have also been reported in other countries.22Dennis JM McGovern AP Vollmer SJ Mateen BA. Improving survival of critical care patients with coronavirus disease 2019 in England: a national cohort study, March to June 2020.Crit Care Med. 2021; 49: 209-214https: //doi.org/10.1007/s00134-020-06294-xGoogle Scholar,23COVID-ICU Group on behalf of the REVA Network and the COVID-ICU InvestigatorsClinical characteristics and day-90 outcomes of 4244 critically ill adults with COVID-19: a prospective cohort study.Intensive Care Med. 2021; 47: 60-73https: //doi.org/10.1007/s00134-020-06294-xGoogle Scholar
The use of steroids, remdesivir, and anticoagulants tended to increase in the later waves. This was likely due to the widespread recognition of the evidence and the approval of remdesivir.24Saito S Hayakawa K Mikami A et al.Investigator initiated clinical trial of remdesivir for the treatment of COVID-19 in Japan.Glob Health Med. 2021; 3: 62-66https: //doi.org/10.35772/ghm.2020.01106Google Scholar As previously discussed,2Matsunaga N Hayakawa K Terada M et al.Clinical epidemiology of hospitalized patients with COVID-19 in Japan: report of the COVID-19 REGISTRY JAPAN.Clin Infect Dis. 2020; Google Scholar patients who were administered favipiravir might have been more likely to be included in our study cohort.
In order to determine the extent to which the data in this study are representative of Japan as a whole, first, we compared the number of infections and deaths in hospitalised patients enrolled in the COVIREGI-JP with those in Japan ( i.e., national data), taking into account regional differences ( Supplementary Table 6, the regions of Japan are shown on the map in Supplementary Figure 1). The coverage rate for infected patients in the COVIREGI-JP of 7·1% ( n=33,554) varied by region, being extremely high in Hokuriku ( 24·8% [ 1,220 ]) and Chugoku ( 17·1% [ 1,680 ]), whereas it was lowest in Kanto ( 5·7% [ 14,229 ]), though the absolute number of cases was high. There was also a difference in the coverage rate depending on the epidemic wave, with Wave 1 covering 32·1% of patients ( n=5,372), but dropped to 14% ( n=11,692) in Wave 2. Wave 3 had 22 times more infected patients than Wave 1, when the rate dropped to 4·4% ( n=16,490). The representativeness of our data might have decreased as the waves progressed. The trend of the highest case fatality rate in Wave 1 and the lowest in Wave 2 in our cohort was also observed in the infected population of Japan. The case fatality rate was higher in this study cohort than in the national data, probably because our cohort included more severe patients as they required hospitalisation. The ratio of case fatality rate between the national data and our data was as follows: 1·4 times ( Wave 1), 2·8 times ( Wave 2), and 2·9 times ( Wave 3). As the wave progressed, patients in our cohort tended to have a higher case fatality rate ratio, suggesting that patients with more severe disease were selected in the later waves. The same trend was observed in each region; however in Hokkaido and Tokai, the case fatality rate in the national data was higher than that in our data in Wave 1, suggesting that there was a discrepancy between the overall regional situation and the trend of registered cases in COVIREGI-JP. The difference in case fatality rates between the nationwide and regional data, in most regions, showed increased or decreased patterns that were consistent between the two data sets ( i.e., national data and COVIREGI-JP data) for each epidemic group. However, in some regions, there were partial divergence. The severity of the cases in COVIREGI-JP might not have been parallel to the severity of the total infected patients in these regions.
We also summarised the number of hospitals in Japan and those participating in the COVIREGI-JP ( Supplementary Table 7). The number of COVIREGI-JP hospitals covered 6·7% ( n=553) of the total number of hospitals in Japan, and in contrast to the gradual decrease in patient coverage, the number of facilities was highest in Wave 2 and was slightly increased in Wave 3 compared to Wave 1. Nearly half of the tertiary care facilities in Japan participated in the COVIREGI-JP, however, in Wave 3, the percentage of tertiary hospitals dropped to about 30% ( n=94). This can be attributed to the fact that medical institutions other than tertiary hospitals treated COVID-19 inpatients due to the expansion of the number of infected patients, as well as that lower number of facilities that registered patients to COVIREGI-JP due to the increased burden of the workload triggered by more infected patients. As for the facility coverage rate, no regional trend similar to that of the number of patients was observed, and the rate was rather high in the Kanto region, where the coverage rate of the number of patients was low. Most of the regions were covered by 30% to 50% of tertiary medical institutions in each epidemic wave, however the number of facilities and tertiary medical institutions in Shikoku tended to be low. In summary, despite partial regional differences, the study cohort had a higher case fatality rate than that reported for total infected population in Japan. Although there was a tendency for the patient coverage rate to decrease in Wave 3, there was no significant increase or decrease in the facility coverage rate. The trend of increase or decrease in the case fatality rate in each wave showed a similar pattern to that of the overall nationwide infected population in Japan.
The study had some limitations. The hospitalisation recommendations changed during the study period; 4Yamada G Hayakawa K Matsunaga N et al.Predicting respiratory failure for COVID-19 patients in Japan: a simple clinical score for evaluating the need for hospitalisation.Epidemiol Infect. 2021; 149: e175https: //doi.org/10.1017/S0950268821001837Google Scholar therefore, patient background and severity of illness were not uniform throughout the study period. The changes in hospitalisation recommendations of the Ministry of Health, Labour and Welfare are summarised in Supplementary Table 5. In the early stages of the epidemic, hospitalisation was recommended for almost all patients. In the middle of Wave 1, the recommendation for recuperation at accommodation facilities or home was issued, and hospitalisation was recommended in principle for the elderly and patients with underlying diseases. At the end of Wave 2, these standards were revised, and the hospitalisation recommendation became more stringent. However, these recommendations were not compulsory, and hospitalisation at the physicians’ discretion might have been adopted, especially when the number of infected people was not significantly high. With regard to diagnosis, the number of tests conducted in Japan was low at the beginning of the epidemic and they increased over time.25Ministry of Health, Labour and Welfare. Situation report. No. of PCR tests conducted. Available at: https: //www.mhlw.go.jp/stf/covid-19/kokunainohasseijoukyou 00006.html. Accessed 10 December 2021.Google Scholar Thus, especially in Wave 1, asymptomatic or mildly ill patients may have remained undiagnosed or the time from infection to diagnosis might have been long. This is probably one of the reasons why the time from onset to hospitalisation was longer in Wave 1 than Waves 2 and 3 and might have contributed to the severity of the disease at the time of hospitalisation in Wave 1, even if the hospitalisation recommendation was less restrictive. These multiple factors may have resulted in more hospitalisations of young people with mild illnesses in Wave 2 than in other waves.
The outcomes of patients who required prolonged hospitalisation might not have been reflected, especially during Wave 3. Overall, 1,943 patients ( 5·5%) were excluded from the study because of non-fixed data. In many cases, information such as outcome at discharge, and supportive care, history of drug administration, and complications during hospitalisation were not fixed. If the data were available, this might change the numbers including the outcome especially during Wave 3. In addition, we defined obesity based on BMI, but it was missing in 6,374 ( 19%) cases, which may have led to underestimation or overestimation of obesity. On the other hand, missing data for important parameters such as age, sex, comorbidity ( other than obesity), oxygen support, and outcome were low, as shown below, and we believe that the impact on the analysis was minimal ( missing data for age: 12 [ 0·04% ], sex: 3 [ 0·01% ], comorbidity: 0, oxygen support: 9 [ 0·03% ], outcome: 24 [ 0·07% ]). Since the first case of the alpha variant was reported in December 2020, there were 678 cases of variants reported in Japan ( mostly the alpha variant) as of the end of March 2021,26Ministry of Health, Labour and Welfare. Number of confirmed variants strains ( genome analysis) by prefecture. March 31, 2021. Available at: https: //www.mhlw.go.jp/content/10900000/000763676.pdf. Accessed 10 December 2021.Google Scholar although these might have been underreported. Unfortunately, there is no information on the variants in this study. However, the impact was considered to be minimal. The other limitations due to the nature of the registry, such as the potential of selection bias and accuracy of data entered at each facility, were previously described.2Matsunaga N Hayakawa K Terada M et al.Clinical epidemiology of hospitalized patients with COVID-19 in Japan: report of the COVID-19 REGISTRY JAPAN.Clin Infect Dis. 2020; Google Scholar As mentioned earlier, based on the rate of vaccination in Japan as a whole, almost all the patients in the present cohort are considered to be unvaccinated; however, detailed data on vaccination history were not available for this analysis. Because the study included patients who were transferred from other hospitals if the selection criteria were met, a patient may have been enrolled more than once for different time periods if they were transferred during a single SARS-CoV-2 infection episode. While this would enable the collection of accurate data on the outcome of each patient's hospitalisation episode, it might have led to an overrepresentation of some parameters, such as demographic data of patients who were transferred, especially for rare events. A total of 1,306 patients were transferred from the institutions participating in the study at the time of admission. Unfortunately, the reason for the transfer was unknown. The summarised characteristics of these patients suggest that there were more severe cases with higher case fatality rate and more frequent invasive treatment ( e.g. IMV or ECMO) than whole cohort. If these cases were included only once in the whole cohort, then the case fatality rate might have been slightly higher. We did not adjust for the drug administration or supportive care in the multivariable analysis, to evaluate the effect of each wave on outcome. As the outcome was better in Wave 3 than in Wave 1 after adjusting for the effects of age and comorbidities, the change of the drug administration and/or supportive care might have affected the outcome.
In conclusion, although the overall case fatality rate remained relatively low, the case fatality rate was approximately twice as high among older patients and varied with the epidemic wave. After adjusting for age and comorbidities, the risk of death was highest in Wave 1. However, it seems difficult to keep the case fatality rate low during waves that include a large number of older patients. Changes in COVID-19 medications and supportive care were observed over time in Japan. These findings present important basic data for understanding future changes due to increased vaccination rates and variants.
The authors declare no conflicts of interest.
Conception/design of the work: NM, KH, YA, ST, and SS.; acquisition of data: NM, MT, SS, HO, KK, AT, KS, MS; analysis of data: YA and ST; drafting of the manuscript: KH. All authors were involved in data interpretation and review of the final manuscript.
We thank all the participating facilities for their care of COVID-19 patients and their cooperation in entering data into the registry.
Data are available upon reasonable request. Data on an individual level is shared with limitation to participating healthcare facilities through applications to COVIREGI-JP.
The Lancet Group takes a neutral position with respect to territorial claims in published maps and institutional affiliations.
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Omicron: fewer adverse outcomes come with new dangers | With wave after wave of SARS-CoV-2 variants, COVID-19 patients filled the worlds ' hospitals and morgues because not everybody had access to vaccines or were willing to be vaccinated.1Tangcharoensathien V Bassett MT Meng Q Mills A Are overwhelmed health systems an inevitable consequence of covid-19? Experiences from China, Thailand, and New York State.BMJ. 2021; 372: n83Google Scholar, 2Dhawan M Priyanka AS Choudhary OP Vaccine inequity and hesitancy: dual factors in the emergence of novel SARS-CoV-2 variants.Ann Med Surg. 2022; 73103186Google Scholar Omicron ( B.1.1.529) is no different. Although most scientists were expecting an increase in cases during late 2021, it was surprising that vaccinated and previously infected people were contracting the novel omicron variant so easily and how fast it was transmitting,3Viana R Moyo S Amoako DG et al.Rapid epidemic expansion of the SARS-CoV-2 omicron variant in southern Africa.Nature. 2022; ( published online Jan 7.) https: //doi.org/10.1038/s41586-022-04411-yGoogle Scholar which raised several questions. Would existing vaccines still prevent SARS-CoV-2 infection? 4Andrews N Stowe J Kirsebom F et al.Effectiveness of COVID-19 vaccines against the omicron ( B. 1.1. 529) variant of concern.medRxiv. 2021; ( published online Dec 14.) ( preprint).https: //doi.org/10.1101/2021.12.14.21267615Google Scholar Was omicron more transmissible than previous variants? 5Lundberg AL Lorenzo-Redondo R Ozer EA et al.Has omicron changed the evolution of the pandemic?.JMIR Public Health Surveill. 2022; 8e35763Google Scholar What were the consequences of omicron's wide and rapid spread infecting millions of people, including a high number of breakthrough cases? Would it have worse or better outcomes than the worst SARS-CoV-2 variant on record, the delta variant ( B.1.617.2)? In The Lancet, Tommy Nyberg and colleagues report their findings about omicron for individuals who are vaccinated, previously infected, or unvaccinated.6Nyberg T Ferguson NM Nash SG et al.Comparative analysis of the risks of hospitalisation and death associated with SARSCoV-2 omicron ( B.1.1.529) and delta ( B.1.617.2) variants in England: a cohort study.Lancet. 2022; ( published online March 16.) https: //doi.org/10.1016/S0140-6736 ( 22) 00462-7Google Scholar This outstanding study included an unparalleled 37% of SARS-CoV-2 cases in England. A longitudinal cohort was analysed when the delta variant was still ongoing and omicron outcompeted delta to become the dominant variant.
Initial omicron studies included fewer cases than included by Nyberg and colleagues6Nyberg T Ferguson NM Nash SG et al.Comparative analysis of the risks of hospitalisation and death associated with SARSCoV-2 omicron ( B.1.1.529) and delta ( B.1.617.2) variants in England: a cohort study.Lancet. 2022; ( published online March 16.) https: //doi.org/10.1016/S0140-6736 ( 22) 00462-7Google Scholar because analysis occurred earlier in the outbreak, such as in South Africa,7Wolter N Jassat W Walaza S et al.Early assessment of the clinical severity of the SARS-CoV-2 omicron variant in South Africa: a data linkage study.Lancet. 2022; 399: 437-446Google Scholar Denmark,8Bager P Wohlfahrt J Bhatt S et al.Reduced risk of hospitalisation associated with infection with SARS-CoV-2 omicron relative to delta: a Danish cohort study.SSRN. 2022; ( published online Jan 14.) ( preprint).https: //ssrn.com/abstract=4008930Google Scholar Norway,9Veneti L Bøås H Kristoffersen AB et al.Reduced risk of hospitalisation among reported COVID-19 cases infected with the SARS-CoV-2 omicron BA. 1 variant compared with the delta variant, Norway, December 2021 to January 2022.Eurosurveillance. 2022; 272200077Google Scholar or Scotland,10Sheikh A Kerr S Woolhouse M McMenamin J Robertson C Severity of omicron variant of concern and vaccine effectiveness against symptomatic disease: national cohort with nested test negative design study in Scotland.Edinburgh Research Explorer. 2021; ( published online Dec 22.) ( preprint).https: //www.pure.ed.ac.uk/ws/portalfiles/portal/245818096/Severity of Omicron variant of concern and vaccine effectiveness against symptomatic disease.pdfGoogle Scholar or were restricted to smaller regions and hospitals. Nyberg and colleagues have conducted the first large scale severity study based on 1 516 702 individuals with COVID-19, of whom 1 067 859 were infected with the omicron variant, using a mix of epidemiological and genetic molecular data.9Veneti L Bøås H Kristoffersen AB et al.Reduced risk of hospitalisation among reported COVID-19 cases infected with the SARS-CoV-2 omicron BA. 1 variant compared with the delta variant, Norway, December 2021 to January 2022.Eurosurveillance. 2022; 272200077Google Scholar This study reports both encouraging and discouraging findings related to decreased severity of disease ( vs delta) and partial vaccine escape, respectively.
Nyberg and colleagues found that the risk of hospitalisation and death due to omicron is substantially lower than for delta. Except for children younger than 10 years, individuals with a documented previous SARS-CoV-2 infection had lower hospitalisations and deaths than for delta, even unvaccinated individuals. However, individuals who had received an mRNA vaccination faired far better than unvaccinated or previously infected individuals. Patients who had been boosted with an mRNA vaccine had 70% fewer adverse outcomes than unvaccinated individuals. This cohort was 53·2% female, all age groups were well represented, and 83·3% participants were White and 5·3% were Black. Comparing omicron with delta, the hazard ratios ( HRs) were 0·56 ( 95% CI 0·54–0·58) for a hospital visit, 0·41 ( 0·39–0·43) for hospital admission, and 0·31 ( 0·26–0·37) for death. Past infection gave protection for omicron and delta variants against death in both vaccinated ( HR 0·47 [ 0·32–0·68 ]) and unvaccinated ( HR 0·18 [ 0·06–0·57 ]) individuals. Notably, for vaccinated individuals, past infection offered no additional protection ( HR 0·96 [ 0·88–1·04 ]).
Coronaviruses in general have significant waning immunity requiring boosters, even with previous infections.11Townsend JP Hassler HB Wang Z et al.The durability of immunity against reinfection by SARS-CoV-2: a comparative evolutionary study.Lancet Microbe. 2021; 2: e666-e675Google Scholar Similarly, immunised individuals or those with previous documented SARS-CoV-2 infections had little protection against contracting the omicron variant, raising the question of whether it is time to develop a novel vaccine more effective against the SARS-CoV-2 infections. Nevertheless, Nyberg and colleagues show that the individual risk of omicron versus delta for severe outcomes ( such as hospitalisations and death) is significantly less. This study also highlights that, although vaccines can not prevent infections or reinfections with the omicron variant, mRNA vaccine boosters still offer a high level of protection against hospitalisations and deaths.
Although this study is timely and an important contribution to the SARS-CoV-2 literature, there are also some limitations. Despite decreased individual risks for hospitalisation and death ( omicron vs delta), Nyberg and colleagues did not emphasise the considerable threat to public health. Given that omicron is more transmissible than the delta variant, there were record levels of cases globally that led to record numbers of hospitalisations in some countries, such as the USA.12Centers for Disease Control and PreventionCOVID data tracker.https: //covid.cdc.gov/covid-data-tracker/ # new-hospital-admissionsDate accessed: March 11, 2022Google Scholar For every new infection, there is the risk of SARS-CoV-2 evolving yet again due to novel mutations, either within the omicron lineages ( such as further evolution of the BA.1 and BA.2 omicron subvariants) or from new independent lineages ( as has happened with every variant of concern thus far). However, as this study shows, omicron has led to a new pandemic scenario where a substantial proportion of the population in countries with high incidence rates has acquired immunity either through vaccination, infection, or both. In this environment, spikes in hospitalisations are rarer due to a combination of pre-existing immunity and selection of less pathogenic SARS-CoV-2 variants, such as omicron. Yet, we can not dismiss the fact that highly pathogenic or transmissible variants might develop. In low-income and middle-income countries where fewer people are vaccinated, SARS-CoV-2 will diversify more rapidly.
The global community must keep pushing for equity in access to COVID-19 vaccines and treatments in countries with low immunisation rates. Preventing the spread of SARS-CoV-2 will obstruct the virus from adapting whilst more directed data-driven prevention measures are implemented in highly immunised countries. With advancing SARS-CoV-2 knowledge—especially from large studies like that of Nyberg and colleagues—together with new and developing vaccines, treatments, and therapeutics, we might be on the precipice of more targeted, preventive measures that allow us to avoid blanket, highly restrictive policies that have harmful costs to the economy, society, and public health.
We declare no competing interests.
Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron ( B.1.1.529) and delta ( B.1.617.2) variants in England: a cohort studyThe risk of severe outcomes following SARS-CoV-2 infection is substantially lower for omicron than for delta, with higher reductions for more severe endpoints and significant variation with age. Underlying the observed risks is a larger reduction in intrinsic severity ( in unvaccinated individuals) counterbalanced by a reduction in vaccine effectiveness. Documented previous SARS-CoV-2 infection offered some protection against hospitalisation and high protection against death in unvaccinated individuals, but only offered additional protection in vaccinated individuals for the death endpoint. Full-Text PDF Open Access | tech |
Covid. War. Inflation. Recession fears. The stock market can't keep up |
It's been a year full of worries for investors, from geopolitical conflict to inflation to the pandemic, and it doesn't look like the concerns will ease anytime soon.
The combination of these major macroeconomic and geopolitical issues will make it difficult for stocks to climb out of their hole and finish 2022 in positive territory, some experts say.
`` There are way too many headwinds to expect good returns for stocks this year, '' said David Spika, president and chief investment officer of GuideStone Capital Management.
Despite big Wall Street rallies the past two days, the
stock market
has tumbled overall in 2022. The
Dow
is down nearly 7% this year, the
S & P 500
has fallen about 10% and the
Nasdaq
is off more than 15%.
Three concerns in particular are weighing on stocks.
Russia's invasion of Ukraine
has pushed oil prices up.
Read More
Before that, investors were already
fretting about inflation
and the likelihood that
the Federal Reserve would raise interest rates
multiple times this year to fight it. Meanwhile,
Covid-19
hasn't gone away, with the
recent spike in cases in China
raising alarm bells.
`` I don't see any way we get positive returns for stocks, '' Spika said, adding that it would be a victory if stocks `` only '' fall in the single digits this year.
Uncertainty continues to weigh on investor sentiment
Spika said it's unreasonable to expect that the Russia-Ukraine crisis will end anytime soon. And even if it did, Spika argues that stock valuations are too high given that interest rates are about to rise.
`` Double-digit percentage drops are possible. The past few years were strong and that was fueled by easy monetary policy, '' he said. `` That tailwind is about to turn into a massive headwind. ''
Stephanie Lang, chief investment officer with Homrich Berg, agreed that `` the age of easy money is over. ''
While the Fed's higher interest rates are high on investors minds, it's only one part of the problem for the stock market.
When will people get fed up with high prices?
`` The list of strains on stocks is pretty long. We have the war, the reminder that the pandemic is endemic and significant, long-lasting disruptions to supply chains, '' said Vincent Reinhart, chief economist at Dreyfus and Mellon. `` Investors are understandably hunkering down. ''
Reinhart added that the Fed will probably raise rates several times this year to try to put a damper on inflation. But there are concerns that the central bank waited too long to raise rates and now may face a stagflation problem, the combination of slow growth and high prices.
`` It's going to be tough for the Fed to get it right, '' Reinhart said. `` Any reasonable person would say that recession risks are more elevated today than six months ago. ''
Lang thinks the central bank `` missed the mark on inflation '' and will have to make more aggressive moves going forward.
The Fed is in a tough spot, but some hope it won't raise rates too sharply
Other experts aren't so sure that major moves are ahead. They say that the Fed recognizes there is a risk of going overboard with rate hikes, and that gradual, small increases may not slow down the economy too drastically. That could mean that the worst may soon be over for stocks.
`` If the Fed overshoots on rate hikes that would be a longer term problem for the economy, '' said Louise Goudy Willmering, a partner with Crewe Advisors. `` But if the Fed isn't too aggressive, we still can have growth. The economy doesn't have to fall off the side of a cliff. ''
Willmering also said that it's way too early to give up on hopes of a market rebound later this year. It's only March, after all.
Of course, it may be tough for stocks to stage to a huge rally like the one following `` the fear induced drop of 2020, '' she said. But she added that if worries about Ukraine and supply chain issues finally subside, earnings growth could return to more normal levels, which would boost stocks.
Biden's plan to reshape the Fed just hit a hurdle
Even if the broader market does continue to struggle, there may be some pockets of strength.
Lang said investors should be looking at quality, safe haven stocks that pay dividends, such as consumer goods companies and healthcare firms. And Spika said energy stocks and smaller companies with more exposure to the US economy than international markets should also do well in a rising rate environment.
Still, even with stocks rebounding as they have the past few days, there may be more volatility ahead — which could create better opportunities for investors.
`` When do you start buying? '' Spika said. `` Once we get clarity about what's going on in Ukraine. '' | general |
Awake prone positioning for non-intubated patients with COVID-19-related acute hypoxaemic respiratory failure: a systematic review and meta-analysis - The Lancet Respiratory Medicine | BackgroundAwake prone positioning has been broadly utilised for non-intubated patients with COVID-19-related acute hypoxaemic respiratory failure, but the results from published randomised controlled trials ( RCTs) in the past year are contradictory. We aimed to systematically synthesise the outcomes associated with awake prone positioning, and evaluate these outcomes in relevant subpopulations.MethodsIn this systematic review and meta-analysis, two independent groups of researchers searched MEDLINE, Embase, PubMed, Web of Science, Scopus, MedRxiv, BioRxiv, and ClinicalTrials.gov for RCTs and observational studies ( with a control group) of awake prone positioning in patients with COVID-19-related acute hypoxaemic respiratory failure published in English from Jan 1, 2020, to Nov 8, 2021. We excluded trials that included patients intubated before or at enrolment, paediatric patients ( ie, younger than 18 years), or trials that did not include the supine position in the control group. The same two independent groups screened studies, extracted the summary data from published reports, and assessed the risk of bias. We used a random-effects meta-analysis to pool individual studies. We used the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the certainty and quality of the evidence. The primary outcome was the reported cumulative intubation risk across RCTs, and effect estimates were calculated as risk ratios ( RR; 95% CI). The analysis was primarily conducted on RCTs, and observational studies were used for sensitivity analyses. No serious adverse events associated with awake prone positioning were reported. The study protocol was prospectively registered with PROSPERO, CRD42021271285.FindingsA total of 1243 studies were identified, we assessed 138 full-text articles and received the aggregated results of three unpublished RCTs; therefore, after exclusions, 29 studies were included in the study. Ten were RCTs ( 1985 patients) and 19 were observational studies ( 2669 patients). In ten RCTs, awake prone positioning compared with the supine position significantly reduced the need for intubation in the overall population ( RR 0·84 [ 95% CI 0·72–0·97 ]). A reduced need for intubation was shown among patients who received advanced respiratory support ( ie, high-flow nasal cannula or non-invasive ventilation) at enrolment ( RR 0·83 [ 0·71–0·97 ]) and in intensive care unit ( ICU) settings ( RR 0·83 [ 0·71–0·97 ]) but not in patients receiving conventional oxygen therapy ( RR 0·87 [ 0·45–1·69 ]) or in non-ICU settings ( RR 0·88 [ 0·44–1·76 ]). No obvious risk of bias and publication bias was found among the included RCTs for the primary outcome.InterpretationIn patients with COVID-19-related acute hypoxaemic respiratory failure, awake prone positioning reduced the need for intubation, particularly among those requiring advanced respiratory support and those in ICU settings. Awake prone positioning should be used in patients who have acute hypoxaemic respiratory failure due to COVID-19 and require advanced respiratory support or are treated in the ICU.FundingOpenAI, Rice Foundation, National Institute for Health Research, and Oxford Biomedical Research Centre.
Awake prone positioning has been broadly utilised for non-intubated patients with COVID-19-related acute hypoxaemic respiratory failure, but the results from published randomised controlled trials ( RCTs) in the past year are contradictory. We aimed to systematically synthesise the outcomes associated with awake prone positioning, and evaluate these outcomes in relevant subpopulations.
In this systematic review and meta-analysis, two independent groups of researchers searched MEDLINE, Embase, PubMed, Web of Science, Scopus, MedRxiv, BioRxiv, and ClinicalTrials.gov for RCTs and observational studies ( with a control group) of awake prone positioning in patients with COVID-19-related acute hypoxaemic respiratory failure published in English from Jan 1, 2020, to Nov 8, 2021. We excluded trials that included patients intubated before or at enrolment, paediatric patients ( ie, younger than 18 years), or trials that did not include the supine position in the control group. The same two independent groups screened studies, extracted the summary data from published reports, and assessed the risk of bias. We used a random-effects meta-analysis to pool individual studies. We used the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the certainty and quality of the evidence. The primary outcome was the reported cumulative intubation risk across RCTs, and effect estimates were calculated as risk ratios ( RR; 95% CI). The analysis was primarily conducted on RCTs, and observational studies were used for sensitivity analyses. No serious adverse events associated with awake prone positioning were reported. The study protocol was prospectively registered with PROSPERO, CRD42021271285.
A total of 1243 studies were identified, we assessed 138 full-text articles and received the aggregated results of three unpublished RCTs; therefore, after exclusions, 29 studies were included in the study. Ten were RCTs ( 1985 patients) and 19 were observational studies ( 2669 patients). In ten RCTs, awake prone positioning compared with the supine position significantly reduced the need for intubation in the overall population ( RR 0·84 [ 95% CI 0·72–0·97 ]). A reduced need for intubation was shown among patients who received advanced respiratory support ( ie, high-flow nasal cannula or non-invasive ventilation) at enrolment ( RR 0·83 [ 0·71–0·97 ]) and in intensive care unit ( ICU) settings ( RR 0·83 [ 0·71–0·97 ]) but not in patients receiving conventional oxygen therapy ( RR 0·87 [ 0·45–1·69 ]) or in non-ICU settings ( RR 0·88 [ 0·44–1·76 ]). No obvious risk of bias and publication bias was found among the included RCTs for the primary outcome.
In patients with COVID-19-related acute hypoxaemic respiratory failure, awake prone positioning reduced the need for intubation, particularly among those requiring advanced respiratory support and those in ICU settings. Awake prone positioning should be used in patients who have acute hypoxaemic respiratory failure due to COVID-19 and require advanced respiratory support or are treated in the ICU.
OpenAI, Rice Foundation, National Institute for Health Research, and Oxford Biomedical Research Centre.
Prone positioning has been shown to improve oxygenation and mortality for intubated patients with moderate to severe acute respiratory distress syndrome ( ARDS),1Guérin C Reignier J Richard JC et al.Prone positioning in severe acute respiratory distress syndrome.N Engl J Med. 2013; 368: 2159-2168Google Scholar, 2Guérin C Albert RK Beitler J et al.Prone position in ARDS patients: why, when, how and for whom.Intensive Care Med. 2020; 46: 2385-2396Google Scholar and it has become the standard of care since the PROSEVA trial was published.3Papazian L Aubron C Brochard L et al.Formal guidelines: management of acute respiratory distress syndrome.Ann Intensive Care. 2019; 9: 69Google Scholar Prone positioning of non-intubated patients, so-called awake prone positioning, has been attempted for patients with acute hypoxaemic respiratory failure, and it has been shown to improve oxygenation and potentially avoid intubation.4Scaravilli V Grasselli G Castagna L et al.Prone positioning improves oxygenation in spontaneously breathing nonintubated patients with hypoxemic acute respiratory failure: a retrospective study.J Crit Care. 2015; 30: 1390-1394Google Scholar, 5Ding L Wang L Ma W He H Efficacy and safety of early prone positioning combined with HFNC or NIV in moderate to severe ARDS: a multi-center prospective cohort study.Crit Care. 2020; 24: 28Google Scholar Similar mechanisms ( ie, better ventilation–perfusion matching and a better homogeneity of lung stress and strain) as pertaining to intubated patients are likely to be involved during awake prone positioning.6Raoof S Nava S Carpati C Hill NS High-flow, noninvasive ventilation and awake ( nonintubation) proning in patients with coronavirus disease 2019 with respiratory failure.Chest. 2020; 158: 1992-2002Google Scholar
Since the early phases of the COVID-19 pandemic, awake prone positioning has been broadly performed worldwide, and it has been recommended by multiple societies,7National Institutes of HealthCOVID-19 treatment guidelines: care of critically ill patients with COVID-19.https: //www.covid19treatmentguidelines.nih.gov/management/critical-care/oxygenation-and-ventilationDate: 2021Date accessed: October 30, 2021Google Scholar, 8Nasa P Azoulay E Khanna AK et al.Expert consensus statements for the management of COVID-19-related acute respiratory failure using a Delphi method.Crit Care. 2021; 25: 106Google Scholar, 9Serpa Neto A Checkley W Sivakorn C Hashmi M Papali A Schultz MJ Pragmatic recommendations for the management of acute respiratory failure and mechanical ventilation in patients with COVID-19 in low and middle-income countries.Am J Trop Med Hyg. 2021; 104: 60-71Google Scholar because of its potential benefits, low risk, and easy implementation. Furthermore, if it is successfully performed outside of the intensive care unit ( ICU), the intervention could spare the very precious resource of ICU bed availability. Multiple observational studies reported improved oxygenation with awake prone positioning, but none of them convincingly demonstrated a benefit in avoiding intubation or reducing mortality.10Pavlov I He H McNicholas B et al.Awake prone positioning in non-intubated patients with acute hypoxemic respiratory failure due to COVID-19: a systematic review of proportional outcomes comparing observational studies with and without awake prone positioning in the setting of COVID-19.Respir Care. 2022; 67: 102-114Google Scholar In August, 2021, an international randomised controlled meta-trial with more than 1100 patients found that awake prone positioning significantly reduced intubation need and treatment failure for patients with COVID-19-related acute hypoxaemic respiratory failure requiring support with high-flow nasal cannula.11Ehrmann S Li J Ibarra-Estrada M et al.Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial.Lancet Respir Med. 2021; 9: 1387-1395Google Scholar However, before this publication, six randomised controlled trials ( RCTs) with a smaller sample size than the meta-trial,12Taylor SP Bundy H Smith WM Skavroneck S Taylor B Kowalkowski MA Awake-prone positioning strategy for non-intubated hypoxic patients with COVID-19: a pilot trial with embedded implementation evaluation.Ann Am Thorac Soc. 2021; 18: 1360-1368Google Scholar, 13Johnson SA Horton DJ Fuller MJ et al.Patient-directed prone positioning in awake patients with COVID-19 requiring hospitalization ( PAPR).Ann Am Thorac Soc. 2021; 18: 1424-1426Google Scholar, 14Rosén J von Oelreich E Fors D et al.Awake prone positioning in patients with hypoxemic respiratory failure due to COVID-19: the PROFLO multicenter randomized clinical trial.Crit Care. 2021; 25: 209Google Scholar, 15Kharat A Dupuis-Lozeron E Cantero C et al.Self-proning in COVID-19 patients on low-flow oxygen therapy: a cluster randomised controlled trial.ERJ Open Res. 2021; 7: 00692-02020Google Scholar, 16Jayakumar D Ramachandran Dnb P Rabindrarajan Dnb E Vijayaraghavan Md BKT Ramakrishnan Ab N Venkataraman Ab R Standard care versus awake prone position in adult nonintubated patients with acute hypoxemic respiratory failure secondary to COVID-19 infection—a multicenter feasibility randomized controlled trial.J Intensive Care Med. 2021; 36: 918-924Google Scholar, 17Gad S Awake prone positioning versus non invasive ventilation for COVID-19 patients with acute hypoxemic respiratory failure.Egypt J Anaesth. 2021; 37: 85-90Google Scholar and two completed but unpublished multi-centre RCTs that enrolled 248 patients18Fralick M Colacci M Munshi L et al.Prone positioning of patients with moderate hypoxia due to COVID-19: a multicenter pragmatic randomized trial [ COVID PRONE ].medRxiv. 2021; ( published online Nov 8, 2021.) ( preprint).https: //doi.org/10.1101/2021.11.05.21264590Google Scholar and 293 patients,19Garcia MA Rampon GL Doros G et al.Rationale and design of the awake prone position for early hypoxemia in COVID-19 ( APPEX-19) study protocol.Ann Am Thorac Soc. 2021; 18: 1560-1566Google Scholar respectively, did not find that awake prone positioning reduced the intubation need for patients with COVID-19; and, three RCTs12Taylor SP Bundy H Smith WM Skavroneck S Taylor B Kowalkowski MA Awake-prone positioning strategy for non-intubated hypoxic patients with COVID-19: a pilot trial with embedded implementation evaluation.Ann Am Thorac Soc. 2021; 18: 1360-1368Google Scholar, 13Johnson SA Horton DJ Fuller MJ et al.Patient-directed prone positioning in awake patients with COVID-19 requiring hospitalization ( PAPR).Ann Am Thorac Soc. 2021; 18: 1424-1426Google Scholar, 18Fralick M Colacci M Munshi L et al.Prone positioning of patients with moderate hypoxia due to COVID-19: a multicenter pragmatic randomized trial [ COVID PRONE ].medRxiv. 2021; ( published online Nov 8, 2021.) ( preprint).https: //doi.org/10.1101/2021.11.05.21264590Google Scholar found that patients ' adherence to awake prone positioning was low. In the two most recent meta-analyses that included RCTs,20Fazzini B Page A Pearse R Puthucheary Z Prone positioning for non-intubated spontaneously breathing patients with acute hypoxaemic respiratory failure: a systematic review and meta-analysis.Br J Anaes. 2022; 128: 352-362Google Scholar, 21Beran A Mhanna M Srour O et al.Effect of prone positioning on clinical outcomes of non-intubated subjects with COVID-19: A comparative systematic review and meta-analysis.Respiratory Care. Nov 2021; ( published online Nov 9, 2021.) https: //doi.org/10.4187/respcare.09362Google Scholar Fazzini and colleagues included two RCTs11Ehrmann S Li J Ibarra-Estrada M et al.Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial.Lancet Respir Med. 2021; 9: 1387-1395Google Scholar, 14Rosén J von Oelreich E Fors D et al.Awake prone positioning in patients with hypoxemic respiratory failure due to COVID-19: the PROFLO multicenter randomized clinical trial.Crit Care. 2021; 25: 209Google Scholar and 12 observational studies, and they reported uncertainty regarding the effects of awake prone positioning on intubation and survival,20Fazzini B Page A Pearse R Puthucheary Z Prone positioning for non-intubated spontaneously breathing patients with acute hypoxaemic respiratory failure: a systematic review and meta-analysis.Br J Anaes. 2022; 128: 352-362Google Scholar whereas Beran and colleagues included five RCTs11Ehrmann S Li J Ibarra-Estrada M et al.Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial.Lancet Respir Med. 2021; 9: 1387-1395Google Scholar, 12Taylor SP Bundy H Smith WM Skavroneck S Taylor B Kowalkowski MA Awake-prone positioning strategy for non-intubated hypoxic patients with COVID-19: a pilot trial with embedded implementation evaluation.Ann Am Thorac Soc. 2021; 18: 1360-1368Google Scholar, 13Johnson SA Horton DJ Fuller MJ et al.Patient-directed prone positioning in awake patients with COVID-19 requiring hospitalization ( PAPR).Ann Am Thorac Soc. 2021; 18: 1424-1426Google Scholar, 14Rosén J von Oelreich E Fors D et al.Awake prone positioning in patients with hypoxemic respiratory failure due to COVID-19: the PROFLO multicenter randomized clinical trial.Crit Care. 2021; 25: 209Google Scholar, 16Jayakumar D Ramachandran Dnb P Rabindrarajan Dnb E Vijayaraghavan Md BKT Ramakrishnan Ab N Venkataraman Ab R Standard care versus awake prone position in adult nonintubated patients with acute hypoxemic respiratory failure secondary to COVID-19 infection—a multicenter feasibility randomized controlled trial.J Intensive Care Med. 2021; 36: 918-924Google Scholar and nine observational studies, and they reported that awake prone positioning has a benefit on mortality.21Beran A Mhanna M Srour O et al.Effect of prone positioning on clinical outcomes of non-intubated subjects with COVID-19: A comparative systematic review and meta-analysis.Respiratory Care. Nov 2021; ( published online Nov 9, 2021.) https: //doi.org/10.4187/respcare.09362Google Scholar
Research in contextEvidence before this studyA large meta-trial demonstrated that awake prone positioning in non-intubated hypoxaemic patients with COVID-19 pneumonia significantly reduced the intubation rate but not the mortality rate, although other randomised controlled trials ( RCTs) showed contradictory results. Two independent groups searched MEDLINE, Embase, PubMed, Web of Science, Scopus, MedRxiv, BioRxiv, and ClinicalTrials.gov for RCTs, observational studies ( with a control group), and meta-analyses of awake prone positioning in patients with COVID-19-related acute hypoxaemic respiratory failure published in English from Jan 1, 2020, to Nov 8, 2021. We included published RCTs comparing awake prone positioning ( intervention group) with the supine position ( control group) for non-intubated adult ( older than 18 years) patients hospitalised for COVID-19 pneumonia. We excluded trials that included patients intubated before or at enrolment, paediatric patients ( younger than 18 years), or trials that did not include the supine position in the control group.Following screening and exclusion of the search results, we identified ten RCTs ( three unpublished from ClinicalTrials.gov), 19 observational studies, and 11 meta-analyses. Only two meta-analyses included RCTs; one included two RCTs and 12 observational studies, and it reported uncertainty in regard to the effects of awake prone positioning on intubation rate and survival; the other meta-analysis included five RCTs and nine observational studies, and it reported that awake prone positioning had a benefit on mortality; this result was probably driven by observational studies.Key search terms were ( prone position *) AND ( awake OR non-intubated) AND ( COVID-19 OR SARS-CoV-2). In general, the quality of the included RCTs was good in terms of randomisation but blinding was not possible due to the nature of prone positioning in awake non-intubated patients. No publication bias was observed among the RCTs for the primary outcome.Added value of this studyAggregating the data of all the available RCTs showed that awake prone positioning reduced the need for intubation in patients with COVID-19-related acute hypoxaemic respiratory failure. We separately analysed the observational studies, and the findings were similar, which strengthens the external validity of these results. Moreover, we found that the reduction in intubation was significant when awake prone positioning was performed in patients in an intensive care unit setting at enrolment and in patients receiving advanced respiratory support ( high-flow nasal cannula or non-invasive ventilation). It was not significant for patients in general wards or in patients receiving conventional oxygen therapy.Implications of all the available evidenceAwake prone positioning should be used in patients with COVID-19-related acute hypoxaemic respiratory failure, in particular when they are managed in the intensive care unit and receive advanced respiratory support.
A large meta-trial demonstrated that awake prone positioning in non-intubated hypoxaemic patients with COVID-19 pneumonia significantly reduced the intubation rate but not the mortality rate, although other randomised controlled trials ( RCTs) showed contradictory results. Two independent groups searched MEDLINE, Embase, PubMed, Web of Science, Scopus, MedRxiv, BioRxiv, and ClinicalTrials.gov for RCTs, observational studies ( with a control group), and meta-analyses of awake prone positioning in patients with COVID-19-related acute hypoxaemic respiratory failure published in English from Jan 1, 2020, to Nov 8, 2021. We included published RCTs comparing awake prone positioning ( intervention group) with the supine position ( control group) for non-intubated adult ( older than 18 years) patients hospitalised for COVID-19 pneumonia. We excluded trials that included patients intubated before or at enrolment, paediatric patients ( younger than 18 years), or trials that did not include the supine position in the control group.
Following screening and exclusion of the search results, we identified ten RCTs ( three unpublished from ClinicalTrials.gov), 19 observational studies, and 11 meta-analyses. Only two meta-analyses included RCTs; one included two RCTs and 12 observational studies, and it reported uncertainty in regard to the effects of awake prone positioning on intubation rate and survival; the other meta-analysis included five RCTs and nine observational studies, and it reported that awake prone positioning had a benefit on mortality; this result was probably driven by observational studies.
Key search terms were ( prone position *) AND ( awake OR non-intubated) AND ( COVID-19 OR SARS-CoV-2). In general, the quality of the included RCTs was good in terms of randomisation but blinding was not possible due to the nature of prone positioning in awake non-intubated patients. No publication bias was observed among the RCTs for the primary outcome.
Aggregating the data of all the available RCTs showed that awake prone positioning reduced the need for intubation in patients with COVID-19-related acute hypoxaemic respiratory failure. We separately analysed the observational studies, and the findings were similar, which strengthens the external validity of these results. Moreover, we found that the reduction in intubation was significant when awake prone positioning was performed in patients in an intensive care unit setting at enrolment and in patients receiving advanced respiratory support ( high-flow nasal cannula or non-invasive ventilation). It was not significant for patients in general wards or in patients receiving conventional oxygen therapy.
Awake prone positioning should be used in patients with COVID-19-related acute hypoxaemic respiratory failure, in particular when they are managed in the intensive care unit and receive advanced respiratory support.
It is crucial to resolve ongoing uncertainties regarding the effects of awake prone positioning on intubation and all-cause mortality for patients with COVID-19-related acute hypoxaemic respiratory failure. Essential to this is to evaluate the effect of awake prone positioning in subpopulations who are likely to benefit differently. These findings can help clinicians in their daily practice and maximise the benefits for patients with COVID-19 during the ongoing pandemic. We performed a systematic review and meta-analysis of all clinical trials with a control group to assess the effect of awake prone positioning on the risk of intubation for patients with COVID-19-related acute hypoxaemic respiratory failure.
We conducted a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses ( PRISMA) recommendations.22Page MJ McKenzie JE Bossuyt PM et al.The PRISMA 2020 statement: an updated guideline for reporting systematic reviews.BMJ. 2021; 372: n71Google Scholar Two independent groups of investigators ( group 1 was JLi, WT, and JLu; group 2 was YP and IP) searched MEDLINE, Embase, PubMed, Web of Science, Scopus, MedRxiv, BioRxiv, Google Scholar, and ClinicalTrials.gov for eligible studies from Jan 1, 2020, to Nov 8, 2021. The key search terms were ( prone position *) AND ( awake or non-intubated) AND ( COVID-19 OR SARS-CoV-2), with the detailed search strategy available in the appendix ( appendix p 5). Only publications in English were included and there was no limit in geographical locations. Summary data were extracted. The status of the trials registered in ClinicalTrials.gov were reviewed, and the authors of RCTs that were completed but not yet published were contacted to obtain their aggregate results.
We included RCTs published in English comparing awake prone positioning ( intervention group) with the supine position ( control group) for non-intubated adult ( older than 18 years) patients hospitalised for COVID-19 pneumonia. Observational studies of awake prone positioning that included a control group ( the supine position) were included as a sensitivity analysis. To evaluate the effects of awake prone positioning on the intubation risk for adult patients with COVID-19, we excluded trials that included patients intubated before or at enrolment, paediatric patients ( younger than 18 years), or trials that did not include the supine position in the control group management; and excluded records that were not observational studies or RCTs—eg, protocols, opinions, editorials, reports. The two investigator groups screened the study titles and abstracts, and reviewed full texts to select the studies; and they independently assessed the risk of bias using the Cochrane collaboration risk of bias tool for RCTs,23Higgins JPT Thomas J Chandler J et al.Cochrane handbook for systematic reviews of interventions version 6·2. 2021. Cochrane.https: //training.cochrane.org/handbook/PDF/v6.2Date accessed: November 25, 2021Google Scholar which considers allocation sequence generation, concealment of allocation, masking of participants and investigators, incomplete outcome reporting, selective outcome reporting, and other sources of bias. Each potential source of bias was graded as high, low, or unclear, which determined whether the studies were considered at high, low, or moderate risk of bias. The Newcastle-Ottawa Scale was used to assess the risk of bias of observational studies, and full details are provided in the appendix ( appendix p 19). Any disagreement regarding study selection, data extraction, or quality assessments was resolved by a consensus discussion with all five investigators and three other members from the meta-analysis group. The protocol is available online.
Data were extracted by the two independent investigator groups in a blinded way, as recommended by the Cochrane Collaboration.23Higgins JPT Thomas J Chandler J et al.Cochrane handbook for systematic reviews of interventions version 6·2. 2021. Cochrane.https: //training.cochrane.org/handbook/PDF/v6.2Date accessed: November 25, 2021Google Scholar Duplicate publications were excluded during screening. A case record form designed for the purpose of the study was used to record information on the following variables: age, sex, body-mass index ( BMI), comorbidities, baseline oxygenation, oxygen devices at enrolment, enrolment location, target and actual awake prone positioning duration, and the use of corticosteroids. Data from each study were tabulated and checked by a third independent author ( ET) before inclusion in the analysis. Categorical outcomes were extracted as the number of patients who had each outcome and the total number of patients in each group ( denominator). Continuous outcomes were extracted as sample size and mean ( SD) or median ( IQR) provided in the studies, with the conversion of medians to estimated mean ( SD).24McGrath S Zhao X Steele R et al.Estimating the sample mean and standard deviation from commonly reported quantiles in meta-analysis.Stat Methods Med Res. 2020; 29 ( 962280219889080) Google Scholar Intention-to-treat datasets were selected if more than one set of results was reported. Authors were contacted in cases of missing data or if the reporting format was not suitable for the meta-analysis—eg, if the data was only presented in a figure. The primary analysis was conducted separately on RCTs and observational studies.
We prespecified outcomes for efficacy on the basis of the consensus of the meta-analysis group. The primary outcome was the cumulative intubation risk across RCTs; the measure of effect was risk ratio ( RR; 95% CI). Secondary outcomes included the reported all-cause mortality; the need for escalating respiratory support, which was defined as progression to a higher level of oxygen or respiratory support ( room air < conventional oxygen therapy < high-flow nasal cannula < non-invasive ventilation [ NIV ] < invasive ventilation) according to the included studies; 11Ehrmann S Li J Ibarra-Estrada M et al.Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial.Lancet Respir Med. 2021; 9: 1387-1395Google Scholar, 12Taylor SP Bundy H Smith WM Skavroneck S Taylor B Kowalkowski MA Awake-prone positioning strategy for non-intubated hypoxic patients with COVID-19: a pilot trial with embedded implementation evaluation.Ann Am Thorac Soc. 2021; 18: 1360-1368Google Scholar, 13Johnson SA Horton DJ Fuller MJ et al.Patient-directed prone positioning in awake patients with COVID-19 requiring hospitalization ( PAPR).Ann Am Thorac Soc. 2021; 18: 1424-1426Google Scholar, 14Rosén J von Oelreich E Fors D et al.Awake prone positioning in patients with hypoxemic respiratory failure due to COVID-19: the PROFLO multicenter randomized clinical trial.Crit Care. 2021; 25: 209Google Scholar, 15Kharat A Dupuis-Lozeron E Cantero C et al.Self-proning in COVID-19 patients on low-flow oxygen therapy: a cluster randomised controlled trial.ERJ Open Res. 2021; 7: 00692-02020Google Scholar, 16Jayakumar D Ramachandran Dnb P Rabindrarajan Dnb E Vijayaraghavan Md BKT Ramakrishnan Ab N Venkataraman Ab R Standard care versus awake prone position in adult nonintubated patients with acute hypoxemic respiratory failure secondary to COVID-19 infection—a multicenter feasibility randomized controlled trial.J Intensive Care Med. 2021; 36: 918-924Google Scholar, 17Gad S Awake prone positioning versus non invasive ventilation for COVID-19 patients with acute hypoxemic respiratory failure.Egypt J Anaesth. 2021; 37: 85-90Google Scholar, 18Fralick M Colacci M Munshi L et al.Prone positioning of patients with moderate hypoxia due to COVID-19: a multicenter pragmatic randomized trial [ COVID PRONE ].medRxiv. 2021; ( published online Nov 8, 2021.) ( preprint).https: //doi.org/10.1101/2021.11.05.21264590Google Scholar, 19Garcia MA Rampon GL Doros G et al.Rationale and design of the awake prone position for early hypoxemia in COVID-19 ( APPEX-19) study protocol.Ann Am Thorac Soc. 2021; 18: 1560-1566Google Scholar the duration of ICU and hospital stay; and safety outcomes, including cardiac arrest, vomiting, and central or arterial line dislodgement. We also performed a post-hoc analysis on ICU admission among patients who were not admitted to the ICU at enrolment and added it as a secondary outcome.
We performed data analysis according to the recommendations in chapter 10 of the Cochrane Handbook for Systematic Reviews and Interventions.23Higgins JPT Thomas J Chandler J et al.Cochrane handbook for systematic reviews of interventions version 6·2. 2021. Cochrane.https: //training.cochrane.org/handbook/PDF/v6.2Date accessed: November 25, 2021Google Scholar Funnel plots were depicted to assess publication bias using the random-effects trim and fill method ( R0 estimator) to correct for small study effects and Egger's test. Effect estimates were calculated as RRs for dichotomous outcomes and mean difference for continuous outcomes. Studies with no events contributed no information for dichotomous outcomes. Data were combined with random effects to account for heterogeneity and fixed effects to evaluate the influence of small studies. The random-effects model was considered as the main analysis. The Mantel-Haenszel method was used for the fixed-effects model.25Mantel N Haenszel W Statistical aspects of the analysis of data from retrospective studies of disease.J Natl Cancer Inst. 1959; 22: 719-748Google Scholar The restricted maximum-likelihood estimator was used to estimate the between study variance for the inverse variance method in random-effects models.26Langan D Higgins JPT Jackson D et al.A comparison of heterogeneity variance estimators in simulated random-effects meta-analyses.Res Synth Methods. 2019; 10: 83-98Google Scholar Statistical heterogeneity assessment between studies was performed by Cochran's Q test and reported with the I2 and Chi squared ( χ2) statistics, in which I2 indicated the degree of heterogeneity as follows: insignificant heterogeneity ( 0–30%), moderate heterogeneity ( 30–60%), substantial heterogeneity ( 50–90%), and considerable heterogeneity ( 75–100%). The threshold for significance for p values was 0·05.
Trial sequential analysis ( TSA) was performed by TSA, version 0.9.5.10 to further test the effect of awake prone positioning, which was achieved by defining the required information size, adjusting the thresholds for statistical significance each time a trial was included using the O'Brien-Fleming boundaries, and introducing the threshold for futility. The subgroup analyses on intubation need were based on respiratory support level before randomisation and patient location at enrolment. With regards to respiratory support level, conventional oxygen therapies without positive pressure such as nasal cannula or a mask were classified as conventional oxygen therapy, and positive airway pressure such as high-flow nasal cannula and NIV were classified as an advanced level of respiratory support. The location at enrolment was ICU versus non-ICU. Intermediate ICU or the emergency department was categorised as ICU, considering the intensity of the care and the ratio of nurses to patients in the emergency department, whereas non-ICU represented general wards.
The Grading of Recommendations Assessment, Development and Evaluation ( GRADE) method was used to grade the quality or certainty of the outcomes and the strength of recommendations.27Guyatt G Oxman AD Akl EA et al.GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables.J Clin Epidemiol. 2011; 64: 383-394Google Scholar
Meta-analyses were conducted using meta package ( version 5.0.1) in R ( version 4.0.3). The review protocol was prospectively registered with PROSPERO, CRD42021271285.
The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.
We identified a total of 1243 studies with our search strategy. We screened 1056 titles and abstracts after 187 duplicates were removed. Of 1056 titles and abstracts, 138 full-text articles were assessed for eligibility. In addition, we contacted the authors of six RCTs who had not published their studies results at the time of conducting this systematic review and meta-analysis and received the aggregated results of three RCTs. We excluded 112 full-text articles; therefore, 29 studies were included in the study ( figure 1). We included ten RCTs11Ehrmann S Li J Ibarra-Estrada M et al.Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial.Lancet Respir Med. 2021; 9: 1387-1395Google Scholar, 12Taylor SP Bundy H Smith WM Skavroneck S Taylor B Kowalkowski MA Awake-prone positioning strategy for non-intubated hypoxic patients with COVID-19: a pilot trial with embedded implementation evaluation.Ann Am Thorac Soc. 2021; 18: 1360-1368Google Scholar, 13Johnson SA Horton DJ Fuller MJ et al.Patient-directed prone positioning in awake patients with COVID-19 requiring hospitalization ( PAPR).Ann Am Thorac Soc. 2021; 18: 1424-1426Google Scholar, 14Rosén J von Oelreich E Fors D et al.Awake prone positioning in patients with hypoxemic respiratory failure due to COVID-19: the PROFLO multicenter randomized clinical trial.Crit Care. 2021; 25: 209Google Scholar, 15Kharat A Dupuis-Lozeron E Cantero C et al.Self-proning in COVID-19 patients on low-flow oxygen therapy: a cluster randomised controlled trial.ERJ Open Res. 2021; 7: 00692-02020Google Scholar, 16Jayakumar D Ramachandran Dnb P Rabindrarajan Dnb E Vijayaraghavan Md BKT Ramakrishnan Ab N Venkataraman Ab R Standard care versus awake prone position in adult nonintubated patients with acute hypoxemic respiratory failure secondary to COVID-19 infection—a multicenter feasibility randomized controlled trial.J Intensive Care Med. 2021; 36: 918-924Google Scholar, 17Gad S Awake prone positioning versus non invasive ventilation for COVID-19 patients with acute hypoxemic respiratory failure.Egypt J Anaesth. 2021; 37: 85-90Google Scholar, 18Fralick M Colacci M Munshi L et al.Prone positioning of patients with moderate hypoxia due to COVID-19: a multicenter pragmatic randomized trial [ COVID PRONE ].medRxiv. 2021; ( published online Nov 8, 2021.) ( preprint).https: //doi.org/10.1101/2021.11.05.21264590Google Scholar, 19Garcia MA Rampon GL Doros G et al.Rationale and design of the awake prone position for early hypoxemia in COVID-19 ( APPEX-19) study protocol.Ann Am Thorac Soc. 2021; 18: 1560-1566Google Scholar ( NCT04853979) that included a total of 1985 patients, and 19 observational studies that included a total of 2669 patients ( the reference list for observational studies [ non-RCTs ] is available in the appendix pp 6–7).Figure 1Study flow diagramView Large Image Figure ViewerDownload Hi-res image Download ( PPT)
Among the 29 included studies, the awake prone positioning procedures were variable, and the targeted daily proning duration varied between 1 h and 16 h, or as long as the patients could tolerate. Different types of initial respiratory support were used in the ten RCTs, of which seven studies12Taylor SP Bundy H Smith WM Skavroneck S Taylor B Kowalkowski MA Awake-prone positioning strategy for non-intubated hypoxic patients with COVID-19: a pilot trial with embedded implementation evaluation.Ann Am Thorac Soc. 2021; 18: 1360-1368Google Scholar, 13Johnson SA Horton DJ Fuller MJ et al.Patient-directed prone positioning in awake patients with COVID-19 requiring hospitalization ( PAPR).Ann Am Thorac Soc. 2021; 18: 1424-1426Google Scholar, 15Kharat A Dupuis-Lozeron E Cantero C et al.Self-proning in COVID-19 patients on low-flow oxygen therapy: a cluster randomised controlled trial.ERJ Open Res. 2021; 7: 00692-02020Google Scholar, 16Jayakumar D Ramachandran Dnb P Rabindrarajan Dnb E Vijayaraghavan Md BKT Ramakrishnan Ab N Venkataraman Ab R Standard care versus awake prone position in adult nonintubated patients with acute hypoxemic respiratory failure secondary to COVID-19 infection—a multicenter feasibility randomized controlled trial.J Intensive Care Med. 2021; 36: 918-924Google Scholar, 17Gad S Awake prone positioning versus non invasive ventilation for COVID-19 patients with acute hypoxemic respiratory failure.Egypt J Anaesth. 2021; 37: 85-90Google Scholar, 18Fralick M Colacci M Munshi L et al.Prone positioning of patients with moderate hypoxia due to COVID-19: a multicenter pragmatic randomized trial [ COVID PRONE ].medRxiv. 2021; ( published online Nov 8, 2021.) ( preprint).https: //doi.org/10.1101/2021.11.05.21264590Google Scholar, 19Garcia MA Rampon GL Doros G et al.Rationale and design of the awake prone position for early hypoxemia in COVID-19 ( APPEX-19) study protocol.Ann Am Thorac Soc. 2021; 18: 1560-1566Google Scholar included patients with a lower level of respiratory support ( ie, conventional oxygen therapy), two studies11Ehrmann S Li J Ibarra-Estrada M et al.Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial.Lancet Respir Med. 2021; 9: 1387-1395Google Scholar, 14Rosén J von Oelreich E Fors D et al.Awake prone positioning in patients with hypoxemic respiratory failure due to COVID-19: the PROFLO multicenter randomized clinical trial.Crit Care. 2021; 25: 209Google Scholar used advanced respiratory support ( ie, high-flow nasal cannula or NIV), and one study ( NCT04853979) applied all the types of respiratory support. Patients were exclusively in an ICU setting in two RCTs,16Jayakumar D Ramachandran Dnb P Rabindrarajan Dnb E Vijayaraghavan Md BKT Ramakrishnan Ab N Venkataraman Ab R Standard care versus awake prone position in adult nonintubated patients with acute hypoxemic respiratory failure secondary to COVID-19 infection—a multicenter feasibility randomized controlled trial.J Intensive Care Med. 2021; 36: 918-924Google Scholar, 17Gad S Awake prone positioning versus non invasive ventilation for COVID-19 patients with acute hypoxemic respiratory failure.Egypt J Anaesth. 2021; 37: 85-90Google Scholar exclusively in a general ward setting in six RCTs12Taylor SP Bundy H Smith WM Skavroneck S Taylor B Kowalkowski MA Awake-prone positioning strategy for non-intubated hypoxic patients with COVID-19: a pilot trial with embedded implementation evaluation.Ann Am Thorac Soc. 2021; 18: 1360-1368Google Scholar, 13Johnson SA Horton DJ Fuller MJ et al.Patient-directed prone positioning in awake patients with COVID-19 requiring hospitalization ( PAPR).Ann Am Thorac Soc. 2021; 18: 1424-1426Google Scholar, 15Kharat A Dupuis-Lozeron E Cantero C et al.Self-proning in COVID-19 patients on low-flow oxygen therapy: a cluster randomised controlled trial.ERJ Open Res. 2021; 7: 00692-02020Google Scholar, 18Fralick M Colacci M Munshi L et al.Prone positioning of patients with moderate hypoxia due to COVID-19: a multicenter pragmatic randomized trial [ COVID PRONE ].medRxiv. 2021; ( published online Nov 8, 2021.) ( preprint).https: //doi.org/10.1101/2021.11.05.21264590Google Scholar, 19Garcia MA Rampon GL Doros G et al.Rationale and design of the awake prone position for early hypoxemia in COVID-19 ( APPEX-19) study protocol.Ann Am Thorac Soc. 2021; 18: 1560-1566Google Scholar ( NCT04853979), and in both settings in two RCTs.11Ehrmann S Li J Ibarra-Estrada M et al.Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial.Lancet Respir Med. 2021; 9: 1387-1395Google Scholar, 14Rosén J von Oelreich E Fors D et al.Awake prone positioning in patients with hypoxemic respiratory failure due to COVID-19: the PROFLO multicenter randomized clinical trial.Crit Care. 2021; 25: 209Google Scholar Further demographic details of each RCT are shown in the table and in the appendix for observational studies ( appendix pp 8–11).TableDemographic details of the included RCTsCountryStudy designEnrolment locationIntervention * For further baseline characteristics of the participants please see the full table in the appendix ( appendix pp 46–47) Control * For further baseline characteristics of the participants please see the full table in the appendix ( appendix pp 46–47) Primary outcomeFollow-up timeSecondary outcome ( s) Ehrmann et al ( 2021) 11Ehrmann S Li J Ibarra-Estrada M et al.Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial.Lancet Respir Med. 2021; 9: 1387-1395Google ScholarUSA, Mexico, Canada, Ireland, France, and SpainMulticentre RCTICU, intermediate care unit, emergency department, and general wards564 participants received awake prone positioning for as long and as frequently as possible; daily median duration 5·0 h ( IQR 1·6–8·8) plus usual care557 participants received usual care ( HFNC) Treatment failure within 28 days of enrolment, defined as intubation or death28 daysIntubation; mortality; use of NIV; length of hospital stay; time to HFNC weaning in patients with treatment success; duration of IMV among intubated patients surviving to day 28; mortality in IMV patients; predefined safety outcomes; physiological response to awake prone positioning, including ROX indexTaylor et al ( 2021) 12Taylor SP Bundy H Smith WM Skavroneck S Taylor B Kowalkowski MA Awake-prone positioning strategy for non-intubated hypoxic patients with COVID-19: a pilot trial with embedded implementation evaluation.Ann Am Thorac Soc. 2021; 18: 1360-1368Google ScholarUSASingle-centre RCTGeneral ward27 participants received awake prone positioning plus usual care13 received usual care ( room air, nasal cannula, HFNC, or NIV) Outcomes relative to the successful implementation of a future definitive RCTUntil discharge or deathS/F; time on S/F < 315; receipt of intensive care; oxygen flow > 6 L/min; intubation; hospital length of stay; hospital mortality at 48 h; safety outcomesJohnson et al ( 2021) 13Johnson SA Horton DJ Fuller MJ et al.Patient-directed prone positioning in awake patients with COVID-19 requiring hospitalization ( PAPR).Ann Am Thorac Soc. 2021; 18: 1424-1426Google ScholarUSASingle-centre RCTGeneral ward15 participants received awake prone positioning every 4 h, with a duration of 1–2 h or as long as tolerated; total median duration 1·6 h ( IQR 0·2–3·1) plus usual care15 participants received usual care ( room air or nasal cannula) The change in P/F at 72 h after admission28 daysThe change in P/F at 48 h; the need for endotracheal intubation; ICU transfer; escalation in oxygen delivery system; the length of stay; ventilator-free days; in-hospital mortalityRosén et al ( 2021) 14Rosén J von Oelreich E Fors D et al.Awake prone positioning in patients with hypoxemic respiratory failure due to COVID-19: the PROFLO multicenter randomized clinical trial.Crit Care. 2021; 25: 209Google ScholarSwedenMulticentre RCTICU and general ward36 participants received awake prone positioning for at least 16 h/day; daily median duration 9·0 h ( IQR 4·4–10·6) plus usual care39 participants received usual care ( HFNC or NIV) Intubation within 30 days after enrolment30 daysDuration of awake prone positioning; use of NIV; time to NIV for patients included with HFNC; use of vasopressors or inotropes; CRRT; ECMO; ventilator-free days; days free of NIV or HFNC; hospital and ICU length of stay; 30-day mortality; WHO-ordinal scale for clinical improvement at 7 and 30 days; adverse eventsKharat et al ( 2021) 15Kharat A Dupuis-Lozeron E Cantero C et al.Self-proning in COVID-19 patients on low-flow oxygen therapy: a cluster randomised controlled trial.ERJ Open Res. 2021; 7: 00692-02020Google ScholarSwitzerlandSingle-centre RCTGeneral ward10 participants received awake prone positioning, self-proning for 12 h/day and alternate body positioning every 4 h; total median duration 4·9 h ( SD 3·6) plus usual care17 participants received usual care ( nasal cannula) Oxygen needs assessed by nasal cannula oxygen flow at 24 h28 daysS/F ratio at 24 h; respiratory and heart rate at 24 h; patient trajectory ( transfer to critical care unit) and potential intervention-related adverse effects as defined by neck pain; position-related discomfort and gastro-oesophageal reflux; intubation; death at 28 daysJayakumar et al ( 2021) 16Jayakumar D Ramachandran Dnb P Rabindrarajan Dnb E Vijayaraghavan Md BKT Ramakrishnan Ab N Venkataraman Ab R Standard care versus awake prone position in adult nonintubated patients with acute hypoxemic respiratory failure secondary to COVID-19 infection—a multicenter feasibility randomized controlled trial.J Intensive Care Med. 2021; 36: 918-924Google ScholarIndiaMulticentre RCTICU30 participants received awake prone positioning for at least 6 h/day plus usual care30 participants received usual care ( nasal cannula, face mask, non-rebreather mask, HFNC, or NIV) The proportion of patients adhering to the protocolUntil discharge or deathProportion of patients requiring escalation of respiratory support; number of h prone and maximum h of continuous prone positioning in a day; the length of stay in ICU; ICU mortality; adverse eventsGad et al ( 2021) 17Gad S Awake prone positioning versus non invasive ventilation for COVID-19 patients with acute hypoxemic respiratory failure.Egypt J Anaesth. 2021; 37: 85-90Google ScholarEgyptSingle-centre RCTICU15 participants received awake prone positioning for 1–2 h each session 3 h apart during waking h for the first 3 days plus usual care15 participants received usual care ( non-rebreather mask) Improvement of oxygenation and avoidance of intubation within the first 3 days of critical care admission.. ICU stay and hospital stayFralick et al ( 2021) 18Fralick M Colacci M Munshi L et al.Prone positioning of patients with moderate hypoxia due to COVID-19: a multicenter pragmatic randomized trial [ COVID PRONE ].medRxiv. 2021; ( published online Nov 8, 2021.) ( preprint).https: //doi.org/10.1101/2021.11.05.21264590Google ScholarCanada, USAMulticentre RCTGeneral ward126 participants received awake prone positioning four times per day ( up to 2 h for each session) and they were encouraged to sleep in the prone position overnight; total median duration 6 h ( IQR 1·5–12·8) in the first 72 h and 0 h ( IQR 0–12) from 72 h to 7 days; plus usual care122 participants received usual care ( nasal cannula, venturi mask, HFNC) A composite of in-hospital death, mechanical ventilation, or worsening respiratory failure defined as requiring at least 60% fraction of inspired oxygen for more than 24 h30 daysThe components of the composite analysed individually; time spent in the prone position; change in S/F; time to recovery ( defined as being on room air for at least 24 h); time to discharge from hospital; and the rate of serious adverse eventsGarcia et al ( 2021) 19Garcia MA Rampon GL Doros G et al.Rationale and design of the awake prone position for early hypoxemia in COVID-19 ( APPEX-19) study protocol.Ann Am Thorac Soc. 2021; 18: 1560-1566Google ScholarUSAMulticentre RCTGeneral ward159 participants received awake prone positioning in up to four 1–2 h daily sessions, and up to 12 h nightly plus usual care134 participants received usual care ( room air, nasal cannula, mask, or HFNC) Progression of acute respiratory failure, composite outcome of either respiratory deterioration ( ie, progression to non-rebreather mask, HFNC, NIV, IMV, or requiring an increase in oxygen ≥2 L/min compared with their baseline) or admission to the ICU14 days ( or until discharge or death) Respiratory deterioration; admission to the ICU; receipt of IMV; hospital mortality; diagnosis of ARDS; median self-reported dyspnoea ( Borg Score); safety outcomes; and compliance with awake prone positioningHarris et al ( NCT04853979) QatarMulticentre RCTGeneral ward31 participants received awake prone positioning for at least 3 h/day and up to 16 h/day plus usual care30 participants received usual care ( nasal cannula, non-rebreather mask, HFNC, or NIV) Escalation of respiratory support within the 30 days of the study30 daysIncidence of intubation within 30 days of enrolment; use of nasal prongs, Hudson mask, non-rebreather mask, NIV, and IMV in each group in the first 3 days of the study; physiological response to prone averaged over days 1–3; P/F or S/F ratio and ROX index at baseline, 1 h after the first prone and daily for 4 days; length of time tolerating proning; 28-day mortality; length of stay in ICU and hospital; duration of IMV; displacement of devices; adverse eventsRCT=randomised controlled trial. ICU=intensive care unit. HFNC=high flow nasal cannula. NIV=non-invasive ventilation. IMV=invasive mechanical ventilation. S/F=ratio of pulse oxygen saturation to fraction of inhaled oxygen. S/F=ratio of pulse oximetric saturation to fraction of inhaled oxygen. P/F=ratio of partial pressure of arterial oxygen to fraction of inhaled oxygen. ROX index= ratio of S/F to respiratory rate. CRRT=continuous renal replacement therapy. ECMO=extracorporeal membrane oxygenation. ARDS=acute respiratory distress syndrome. * For further baseline characteristics of the participants please see the full table in the appendix ( appendix pp 46–47) Open table in a new tab
RCT=randomised controlled trial. ICU=intensive care unit. HFNC=high flow nasal cannula. NIV=non-invasive ventilation. IMV=invasive mechanical ventilation. S/F=ratio of pulse oxygen saturation to fraction of inhaled oxygen. S/F=ratio of pulse oximetric saturation to fraction of inhaled oxygen. P/F=ratio of partial pressure of arterial oxygen to fraction of inhaled oxygen. ROX index= ratio of S/F to respiratory rate. CRRT=continuous renal replacement therapy. ECMO=extracorporeal membrane oxygenation. ARDS=acute respiratory distress syndrome.
None of the included RCTs had incomplete or selective outcome data reporting. All RCTs except for one,13Johnson SA Horton DJ Fuller MJ et al.Patient-directed prone positioning in awake patients with COVID-19 requiring hospitalization ( PAPR).Ann Am Thorac Soc. 2021; 18: 1424-1426Google Scholar had a clear description of random sequence generation, six RCTs11Ehrmann S Li J Ibarra-Estrada M et al.Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial.Lancet Respir Med. 2021; 9: 1387-1395Google Scholar, 14Rosén J von Oelreich E Fors D et al.Awake prone positioning in patients with hypoxemic respiratory failure due to COVID-19: the PROFLO multicenter randomized clinical trial.Crit Care. 2021; 25: 209Google Scholar, 16Jayakumar D Ramachandran Dnb P Rabindrarajan Dnb E Vijayaraghavan Md BKT Ramakrishnan Ab N Venkataraman Ab R Standard care versus awake prone position in adult nonintubated patients with acute hypoxemic respiratory failure secondary to COVID-19 infection—a multicenter feasibility randomized controlled trial.J Intensive Care Med. 2021; 36: 918-924Google Scholar, 18Fralick M Colacci M Munshi L et al.Prone positioning of patients with moderate hypoxia due to COVID-19: a multicenter pragmatic randomized trial [ COVID PRONE ].medRxiv. 2021; ( published online Nov 8, 2021.) ( preprint).https: //doi.org/10.1101/2021.11.05.21264590Google Scholar, 19Garcia MA Rampon GL Doros G et al.Rationale and design of the awake prone position for early hypoxemia in COVID-19 ( APPEX-19) study protocol.Ann Am Thorac Soc. 2021; 18: 1560-1566Google Scholar ( NCT04853979) also explained the concealment of allocations ( appendix p 12). Due to the nature of prone positioning in non-intubated patients, masking participants or the treating clinicians was not possible. No obvious publication bias was observed among the RCTs in terms of the primary outcome ( appendix pp 13–18). The summaries of the bias assessment of observational studies indicated potential reporting bias on mortality ( appendix pp 19–21). The GRADE assessment for the certainty of evidence for primary and secondary outcomes is summarised in the appendix ( appendix p 22).
All the RCTs reported patients requiring intubation as an outcome, two RCTs12Taylor SP Bundy H Smith WM Skavroneck S Taylor B Kowalkowski MA Awake-prone positioning strategy for non-intubated hypoxic patients with COVID-19: a pilot trial with embedded implementation evaluation.Ann Am Thorac Soc. 2021; 18: 1360-1368Google Scholar, 15Kharat A Dupuis-Lozeron E Cantero C et al.Self-proning in COVID-19 patients on low-flow oxygen therapy: a cluster randomised controlled trial.ERJ Open Res. 2021; 7: 00692-02020Google Scholar did not report any patients requiring intubation in either the awake prone positioning group or the supine position ( control) group; the remaining studies11Ehrmann S Li J Ibarra-Estrada M et al.Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial.Lancet Respir Med. 2021; 9: 1387-1395Google Scholar, 13Johnson SA Horton DJ Fuller MJ et al.Patient-directed prone positioning in awake patients with COVID-19 requiring hospitalization ( PAPR).Ann Am Thorac Soc. 2021; 18: 1424-1426Google Scholar, 14Rosén J von Oelreich E Fors D et al.Awake prone positioning in patients with hypoxemic respiratory failure due to COVID-19: the PROFLO multicenter randomized clinical trial.Crit Care. 2021; 25: 209Google Scholar, 16Jayakumar D Ramachandran Dnb P Rabindrarajan Dnb E Vijayaraghavan Md BKT Ramakrishnan Ab N Venkataraman Ab R Standard care versus awake prone position in adult nonintubated patients with acute hypoxemic respiratory failure secondary to COVID-19 infection—a multicenter feasibility randomized controlled trial.J Intensive Care Med. 2021; 36: 918-924Google Scholar, 17Gad S Awake prone positioning versus non invasive ventilation for COVID-19 patients with acute hypoxemic respiratory failure.Egypt J Anaesth. 2021; 37: 85-90Google Scholar, 18Fralick M Colacci M Munshi L et al.Prone positioning of patients with moderate hypoxia due to COVID-19: a multicenter pragmatic randomized trial [ COVID PRONE ].medRxiv. 2021; ( published online Nov 8, 2021.) ( preprint).https: //doi.org/10.1101/2021.11.05.21264590Google Scholar, 19Garcia MA Rampon GL Doros G et al.Rationale and design of the awake prone position for early hypoxemia in COVID-19 ( APPEX-19) study protocol.Ann Am Thorac Soc. 2021; 18: 1560-1566Google Scholar ( NCT04853979) showed that awake prone positioning significantly reduced the need for intubation ( RR 0·84 [ 95% CI 0·72–0·97 ]; figure 2).Figure 2Intubation ( A) and mortality ( B) for included randomised controlled trialsView Large Image Figure ViewerDownload Hi-res image Download ( PPT)
In the subgroup analysis, the significant reduction in intubation requirement was observed in RCTs11Ehrmann S Li J Ibarra-Estrada M et al.Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial.Lancet Respir Med. 2021; 9: 1387-1395Google Scholar, 14Rosén J von Oelreich E Fors D et al.Awake prone positioning in patients with hypoxemic respiratory failure due to COVID-19: the PROFLO multicenter randomized clinical trial.Crit Care. 2021; 25: 209Google Scholar ( NCT04853979) that included patients on advanced respiratory support at enrolment ( RR 0·83 [ 95% CI 0·71–0·97 ]), and RCTs11Ehrmann S Li J Ibarra-Estrada M et al.Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial.Lancet Respir Med. 2021; 9: 1387-1395Google Scholar, 16Jayakumar D Ramachandran Dnb P Rabindrarajan Dnb E Vijayaraghavan Md BKT Ramakrishnan Ab N Venkataraman Ab R Standard care versus awake prone position in adult nonintubated patients with acute hypoxemic respiratory failure secondary to COVID-19 infection—a multicenter feasibility randomized controlled trial.J Intensive Care Med. 2021; 36: 918-924Google Scholar, 17Gad S Awake prone positioning versus non invasive ventilation for COVID-19 patients with acute hypoxemic respiratory failure.Egypt J Anaesth. 2021; 37: 85-90Google Scholar that included patients who were in ICU settings at enrolment ( RR 0·83 [ 0·71–0·97 ]), but not for RCTs12Taylor SP Bundy H Smith WM Skavroneck S Taylor B Kowalkowski MA Awake-prone positioning strategy for non-intubated hypoxic patients with COVID-19: a pilot trial with embedded implementation evaluation.Ann Am Thorac Soc. 2021; 18: 1360-1368Google Scholar, 13Johnson SA Horton DJ Fuller MJ et al.Patient-directed prone positioning in awake patients with COVID-19 requiring hospitalization ( PAPR).Ann Am Thorac Soc. 2021; 18: 1424-1426Google Scholar, 15Kharat A Dupuis-Lozeron E Cantero C et al.Self-proning in COVID-19 patients on low-flow oxygen therapy: a cluster randomised controlled trial.ERJ Open Res. 2021; 7: 00692-02020Google Scholar, 16Jayakumar D Ramachandran Dnb P Rabindrarajan Dnb E Vijayaraghavan Md BKT Ramakrishnan Ab N Venkataraman Ab R Standard care versus awake prone position in adult nonintubated patients with acute hypoxemic respiratory failure secondary to COVID-19 infection—a multicenter feasibility randomized controlled trial.J Intensive Care Med. 2021; 36: 918-924Google Scholar, 17Gad S Awake prone positioning versus non invasive ventilation for COVID-19 patients with acute hypoxemic respiratory failure.Egypt J Anaesth. 2021; 37: 85-90Google Scholar, 18Fralick M Colacci M Munshi L et al.Prone positioning of patients with moderate hypoxia due to COVID-19: a multicenter pragmatic randomized trial [ COVID PRONE ].medRxiv. 2021; ( published online Nov 8, 2021.) ( preprint).https: //doi.org/10.1101/2021.11.05.21264590Google Scholar, 19Garcia MA Rampon GL Doros G et al.Rationale and design of the awake prone position for early hypoxemia in COVID-19 ( APPEX-19) study protocol.Ann Am Thorac Soc. 2021; 18: 1560-1566Google Scholar ( NCT04853979) that included patients on conventional oxygen therapy at enrolment ( RR 0·87 [ 0·45–1·69 ]) or RCTs11Ehrmann S Li J Ibarra-Estrada M et al.Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial.Lancet Respir Med. 2021; 9: 1387-1395Google Scholar, 12Taylor SP Bundy H Smith WM Skavroneck S Taylor B Kowalkowski MA Awake-prone positioning strategy for non-intubated hypoxic patients with COVID-19: a pilot trial with embedded implementation evaluation.Ann Am Thorac Soc. 2021; 18: 1360-1368Google Scholar, 13Johnson SA Horton DJ Fuller MJ et al.Patient-directed prone positioning in awake patients with COVID-19 requiring hospitalization ( PAPR).Ann Am Thorac Soc. 2021; 18: 1424-1426Google Scholar, 15Kharat A Dupuis-Lozeron E Cantero C et al.Self-proning in COVID-19 patients on low-flow oxygen therapy: a cluster randomised controlled trial.ERJ Open Res. 2021; 7: 00692-02020Google Scholar, 18Fralick M Colacci M Munshi L et al.Prone positioning of patients with moderate hypoxia due to COVID-19: a multicenter pragmatic randomized trial [ COVID PRONE ].medRxiv. 2021; ( published online Nov 8, 2021.) ( preprint).https: //doi.org/10.1101/2021.11.05.21264590Google Scholar, 19Garcia MA Rampon GL Doros G et al.Rationale and design of the awake prone position for early hypoxemia in COVID-19 ( APPEX-19) study protocol.Ann Am Thorac Soc. 2021; 18: 1560-1566Google Scholar ( NCT04853979) that included patients in non-ICU settings at enrolment ( RR 0·88 [ 0·44–1·76 ]; figure 3). The test for subgroup differences did not demonstrate any statistically significant interaction between intubation risk and enrolment location ( ICU vs non-ICU χ2=0·03; p=0·86; figure 3) or the type of respiratory support ( advanced vs conventional respiratory support χ2=0·02; p=0·88; figure 3). TSA confirmed these findings by showing that the optimal information size was reached ( close to the optimal information size for advanced respiratory support and ICU subgroups) and the crossing of the significance boundaries ( appendix p 23–25). The 18 observational studies with data on intubation also reported a lower risk of intubation in the awake prone positioning group ( RR 0·62 [ 95% CI 0·47–0·83 ]) but with significant statistical heterogeneity ( I2 =65%; χ2= 48·51; p < 0·0001; appendix p 26).Figure 3Subgroup analysis of intubationShow full caption ( A) Advanced versus conventional respiratory support. ( B) ICU versus non-ICU. ICU=intensive care unit.View Large Image Figure ViewerDownload Hi-res image Download ( PPT)
( A) Advanced versus conventional respiratory support. ( B) ICU versus non-ICU. ICU=intensive care unit.
In the ten RCTs with data on mortality, two RCTs12Taylor SP Bundy H Smith WM Skavroneck S Taylor B Kowalkowski MA Awake-prone positioning strategy for non-intubated hypoxic patients with COVID-19: a pilot trial with embedded implementation evaluation.Ann Am Thorac Soc. 2021; 18: 1360-1368Google Scholar, 15Kharat A Dupuis-Lozeron E Cantero C et al.Self-proning in COVID-19 patients on low-flow oxygen therapy: a cluster randomised controlled trial.ERJ Open Res. 2021; 7: 00692-02020Google Scholar reported no deaths in either the awake prone positioning group or the supine position group. The pooled estimates demonstrated that awake prone positioning did not significantly reduce mortality ( RR 1·00 [ 95% CI 0·70–1·44 ]; figure 2). Moreover, no significant differences in mortality were found in the subgroup analyses, which included types of respiratory support at enrolment ( advanced respiratory support RR 1·23 [ 95% CI 0·54–2·80 ]; conventional oxygen therapy RR 1·14 [ 0·47–2·75 ]) or enrolment location ( ICU RR 0·90 [ 0·72–1·13 ]; non-ICU RR 0·81 [ 0·41–1·59 ]; appendix p 27). No significant correlation was found in treatment interaction between types of respiratory support or enrolment locations and mortality ( advanced vs conventional respiratory support χ2=0·02, p=0·90; ICU vs non-ICU χ2=0·08, p=0·77; appendix p 27). However, TSA showed that the optimal information size was not reached, except for the non-ICU subgroup ( appendix pp 28–30). On the contrary, a significant reduction in mortality was found in the 17 observational studies that reported this outcome ( RR 0·56 [ 95% CI 0·48–0·65 ]; appendix p 26). Due to the observation of significant publication biases for mortality in RCTs and observational studies, further pooled estimates were calculated after exclusion of the studies identified as small-study effects by trim and fill ( including five RCTs13Johnson SA Horton DJ Fuller MJ et al.Patient-directed prone positioning in awake patients with COVID-19 requiring hospitalization ( PAPR).Ann Am Thorac Soc. 2021; 18: 1424-1426Google Scholar, 14Rosén J von Oelreich E Fors D et al.Awake prone positioning in patients with hypoxemic respiratory failure due to COVID-19: the PROFLO multicenter randomized clinical trial.Crit Care. 2021; 25: 209Google Scholar, 16Jayakumar D Ramachandran Dnb P Rabindrarajan Dnb E Vijayaraghavan Md BKT Ramakrishnan Ab N Venkataraman Ab R Standard care versus awake prone position in adult nonintubated patients with acute hypoxemic respiratory failure secondary to COVID-19 infection—a multicenter feasibility randomized controlled trial.J Intensive Care Med. 2021; 36: 918-924Google Scholar, 17Gad S Awake prone positioning versus non invasive ventilation for COVID-19 patients with acute hypoxemic respiratory failure.Egypt J Anaesth. 2021; 37: 85-90Google Scholar [ NCT04853979 ] and five observational studies [ references 6,12,14,15,17 in appendix pp 6–7 ]); and the results were similar to the results presented before the exclusion of these studies ( RCTs RR 0·88 [ 95% CI 0·70–1·09 ]; observational studies RR 0·58 [ 0·50–0·68 ]; appendix pp 31–32)
Seven RCTs11Ehrmann S Li J Ibarra-Estrada M et al.Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial.Lancet Respir Med. 2021; 9: 1387-1395Google Scholar, 13Johnson SA Horton DJ Fuller MJ et al.Patient-directed prone positioning in awake patients with COVID-19 requiring hospitalization ( PAPR).Ann Am Thorac Soc. 2021; 18: 1424-1426Google Scholar, 15Kharat A Dupuis-Lozeron E Cantero C et al.Self-proning in COVID-19 patients on low-flow oxygen therapy: a cluster randomised controlled trial.ERJ Open Res. 2021; 7: 00692-02020Google Scholar, 16Jayakumar D Ramachandran Dnb P Rabindrarajan Dnb E Vijayaraghavan Md BKT Ramakrishnan Ab N Venkataraman Ab R Standard care versus awake prone position in adult nonintubated patients with acute hypoxemic respiratory failure secondary to COVID-19 infection—a multicenter feasibility randomized controlled trial.J Intensive Care Med. 2021; 36: 918-924Google Scholar, 18Fralick M Colacci M Munshi L et al.Prone positioning of patients with moderate hypoxia due to COVID-19: a multicenter pragmatic randomized trial [ COVID PRONE ].medRxiv. 2021; ( published online Nov 8, 2021.) ( preprint).https: //doi.org/10.1101/2021.11.05.21264590Google Scholar, 19Garcia MA Rampon GL Doros G et al.Rationale and design of the awake prone position for early hypoxemia in COVID-19 ( APPEX-19) study protocol.Ann Am Thorac Soc. 2021; 18: 1560-1566Google Scholar ( NCT04853979) reported the need for escalation of respiratory support as an outcome; there was no significant difference between the awake prone positioning group and the control groups on the need for escalation of respiratory support ( RR 1·03 [ 95% CI 0·77–1·37 ]; appendix p 33), regardless of the subgroups of respiratory support ( advanced respiratory support RR 1·06 [ 95% CI 0·39–2·89 ]; conventional oxygen therapy RR 0·77 [ 0·43–1·39 ]) or enrolment location ( ICU RR 1·08 [ 0·60–1·96 ]; non-ICU RR 1·0 [ 0·69–1·44 ]; appendix p 34). From the six RCTs11Ehrmann S Li J Ibarra-Estrada M et al.Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial.Lancet Respir Med. 2021; 9: 1387-1395Google Scholar, 12Taylor SP Bundy H Smith WM Skavroneck S Taylor B Kowalkowski MA Awake-prone positioning strategy for non-intubated hypoxic patients with COVID-19: a pilot trial with embedded implementation evaluation.Ann Am Thorac Soc. 2021; 18: 1360-1368Google Scholar, 13Johnson SA Horton DJ Fuller MJ et al.Patient-directed prone positioning in awake patients with COVID-19 requiring hospitalization ( PAPR).Ann Am Thorac Soc. 2021; 18: 1424-1426Google Scholar, 15Kharat A Dupuis-Lozeron E Cantero C et al.Self-proning in COVID-19 patients on low-flow oxygen therapy: a cluster randomised controlled trial.ERJ Open Res. 2021; 7: 00692-02020Google Scholar, 19Garcia MA Rampon GL Doros G et al.Rationale and design of the awake prone position for early hypoxemia in COVID-19 ( APPEX-19) study protocol.Ann Am Thorac Soc. 2021; 18: 1560-1566Google Scholar ( NCT04853979) that reported the need for ICU admission as an outcome, no significant difference was found between the awake prone positioning group and the control groups ( RR 0·75 [ 95% CI 0·51–1·10 ]; appendix p 33) or in the subgroup analysis of respiratory support ( advanced respiratory support RR 0·77 [ 95% CI 0·53–1·11 ]; conventional oxygen therapy RR 0·91 [ 0·56–1·50 ]; appendix p 35), and a similar result was shown after exclusion of a small study13Johnson SA Horton DJ Fuller MJ et al.Patient-directed prone positioning in awake patients with COVID-19 requiring hospitalization ( PAPR).Ann Am Thorac Soc. 2021; 18: 1424-1426Google Scholar identified by trim and fill ( RR 0·69 [ 0·47–1·03 ]; appendix p 36). Furthermore, awake prone positioning did not significantly reduce the ICU length of stay in five RCTs11Ehrmann S Li J Ibarra-Estrada M et al.Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial.Lancet Respir Med. 2021; 9: 1387-1395Google Scholar, 14Rosén J von Oelreich E Fors D et al.Awake prone positioning in patients with hypoxemic respiratory failure due to COVID-19: the PROFLO multicenter randomized clinical trial.Crit Care. 2021; 25: 209Google Scholar, 16Jayakumar D Ramachandran Dnb P Rabindrarajan Dnb E Vijayaraghavan Md BKT Ramakrishnan Ab N Venkataraman Ab R Standard care versus awake prone position in adult nonintubated patients with acute hypoxemic respiratory failure secondary to COVID-19 infection—a multicenter feasibility randomized controlled trial.J Intensive Care Med. 2021; 36: 918-924Google Scholar, 17Gad S Awake prone positioning versus non invasive ventilation for COVID-19 patients with acute hypoxemic respiratory failure.Egypt J Anaesth. 2021; 37: 85-90Google Scholar ( NCT04853979), ( mean difference 0·08 day [ 95% CI –0·89 to 1·05 ]) or hospital length of stay in eight RCTs11Ehrmann S Li J Ibarra-Estrada M et al.Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial.Lancet Respir Med. 2021; 9: 1387-1395Google Scholar, 12Taylor SP Bundy H Smith WM Skavroneck S Taylor B Kowalkowski MA Awake-prone positioning strategy for non-intubated hypoxic patients with COVID-19: a pilot trial with embedded implementation evaluation.Ann Am Thorac Soc. 2021; 18: 1360-1368Google Scholar, 13Johnson SA Horton DJ Fuller MJ et al.Patient-directed prone positioning in awake patients with COVID-19 requiring hospitalization ( PAPR).Ann Am Thorac Soc. 2021; 18: 1424-1426Google Scholar, 14Rosén J von Oelreich E Fors D et al.Awake prone positioning in patients with hypoxemic respiratory failure due to COVID-19: the PROFLO multicenter randomized clinical trial.Crit Care. 2021; 25: 209Google Scholar, 15Kharat A Dupuis-Lozeron E Cantero C et al.Self-proning in COVID-19 patients on low-flow oxygen therapy: a cluster randomised controlled trial.ERJ Open Res. 2021; 7: 00692-02020Google Scholar, 17Gad S Awake prone positioning versus non invasive ventilation for COVID-19 patients with acute hypoxemic respiratory failure.Egypt J Anaesth. 2021; 37: 85-90Google Scholar, 19Garcia MA Rampon GL Doros G et al.Rationale and design of the awake prone position for early hypoxemia in COVID-19 ( APPEX-19) study protocol.Ann Am Thorac Soc. 2021; 18: 1560-1566Google Scholar ( NCT04853979), ( mean difference 0·57 day [ –0·35 to 1·49 ]; appendix p 33). However, in the subgroups of conventional oxygen therapy and non-ICU, a small but significant difference in length of hospital length of stay was found in the awake prone positioning group ( conventional oxygen therapy mean difference 1·15 days [ 95% CI 0·26–2·05 ]; non-ICU mean difference 1·16 days [ 0·27–2·05 ]; appendix pp 37–38). TSA showed that the optimal information size was not reached for any of these secondary outcomes but the need for ICU admission crossed the futility boundary ( appendix pp 39–42). Similar results of secondary outcomes were shown in observational studies ( appendix p 43).
Adverse events were reported in seven RCTs11Ehrmann S Li J Ibarra-Estrada M et al.Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial.Lancet Respir Med. 2021; 9: 1387-1395Google Scholar, 12Taylor SP Bundy H Smith WM Skavroneck S Taylor B Kowalkowski MA Awake-prone positioning strategy for non-intubated hypoxic patients with COVID-19: a pilot trial with embedded implementation evaluation.Ann Am Thorac Soc. 2021; 18: 1360-1368Google Scholar, 14Rosén J von Oelreich E Fors D et al.Awake prone positioning in patients with hypoxemic respiratory failure due to COVID-19: the PROFLO multicenter randomized clinical trial.Crit Care. 2021; 25: 209Google Scholar, 15Kharat A Dupuis-Lozeron E Cantero C et al.Self-proning in COVID-19 patients on low-flow oxygen therapy: a cluster randomised controlled trial.ERJ Open Res. 2021; 7: 00692-02020Google Scholar, 16Jayakumar D Ramachandran Dnb P Rabindrarajan Dnb E Vijayaraghavan Md BKT Ramakrishnan Ab N Venkataraman Ab R Standard care versus awake prone position in adult nonintubated patients with acute hypoxemic respiratory failure secondary to COVID-19 infection—a multicenter feasibility randomized controlled trial.J Intensive Care Med. 2021; 36: 918-924Google Scholar, 19Garcia MA Rampon GL Doros G et al.Rationale and design of the awake prone position for early hypoxemia in COVID-19 ( APPEX-19) study protocol.Ann Am Thorac Soc. 2021; 18: 1560-1566Google Scholar ( NCT04853979) with one RCT12Taylor SP Bundy H Smith WM Skavroneck S Taylor B Kowalkowski MA Awake-prone positioning strategy for non-intubated hypoxic patients with COVID-19: a pilot trial with embedded implementation evaluation.Ann Am Thorac Soc. 2021; 18: 1360-1368Google Scholar showing no complications in either group, and six RCTs reporting mild complications, such as skin breakdown, central venous or arterial line dislodgement, vomiting, back pain, bloating sensation, and general discomfort ( appendix pp 44–45).
In this systematic review and meta-analysis, we found that awake prone positioning significantly reduced the need for intubation of patients with COVID-19-related acute hypoxaemic respiratory failure, in particular among patients who required advanced respiratory support including high-flow nasal cannula or NIV and those who were in an ICU setting at enrolment. This aligns with the findings in the recently published meta-trial,11Ehrmann S Li J Ibarra-Estrada M et al.Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial.Lancet Respir Med. 2021; 9: 1387-1395Google Scholar which enrolled 1121 patients with COVID-19-related acute hypoxaemic respiratory failure who were supported with high-flow nasal cannula; 94% of these patients were in an ICU setting at enrolment. In contrast, none of the seven RCTs, which included a total of 688 patients,12Taylor SP Bundy H Smith WM Skavroneck S Taylor B Kowalkowski MA Awake-prone positioning strategy for non-intubated hypoxic patients with COVID-19: a pilot trial with embedded implementation evaluation.Ann Am Thorac Soc. 2021; 18: 1360-1368Google Scholar, 13Johnson SA Horton DJ Fuller MJ et al.Patient-directed prone positioning in awake patients with COVID-19 requiring hospitalization ( PAPR).Ann Am Thorac Soc. 2021; 18: 1424-1426Google Scholar, 15Kharat A Dupuis-Lozeron E Cantero C et al.Self-proning in COVID-19 patients on low-flow oxygen therapy: a cluster randomised controlled trial.ERJ Open Res. 2021; 7: 00692-02020Google Scholar, 16Jayakumar D Ramachandran Dnb P Rabindrarajan Dnb E Vijayaraghavan Md BKT Ramakrishnan Ab N Venkataraman Ab R Standard care versus awake prone position in adult nonintubated patients with acute hypoxemic respiratory failure secondary to COVID-19 infection—a multicenter feasibility randomized controlled trial.J Intensive Care Med. 2021; 36: 918-924Google Scholar, 17Gad S Awake prone positioning versus non invasive ventilation for COVID-19 patients with acute hypoxemic respiratory failure.Egypt J Anaesth. 2021; 37: 85-90Google Scholar, 18Fralick M Colacci M Munshi L et al.Prone positioning of patients with moderate hypoxia due to COVID-19: a multicenter pragmatic randomized trial [ COVID PRONE ].medRxiv. 2021; ( published online Nov 8, 2021.) ( preprint).https: //doi.org/10.1101/2021.11.05.21264590Google Scholar, 19Garcia MA Rampon GL Doros G et al.Rationale and design of the awake prone position for early hypoxemia in COVID-19 ( APPEX-19) study protocol.Ann Am Thorac Soc. 2021; 18: 1560-1566Google Scholar that enrolled patients supported with conventional oxygen therapy demonstrated a difference in the need for intubation between awake prone positioning and the supine position.
The findings in the subgroup analysis of patients with COVID-19 requiring different levels of respiratory support and treatment in different locations ( ie, ICU vs non-ICU) might have several explanations. The provision of advanced respiratory support and an ICU setting are directly correlated. Taken together, the apparent lack of efficacy of awake prone positioning in less severely ill patients ( non-ICU or receiving conventional oxygen therapy) could be related to a lower event rate, less intensive monitoring, lower nursing to patient ratios, lower adherence to awake prone positioning, and differences in the patient's disease severity. First, patients who require advanced respiratory support or ICU admission are sicker, and they are more likely to progress to invasive mechanical ventilation than patients supported with conventional oxygen therapy. When the event rate is low with large variances, precision is lower. Although the point estimates of relative risk were similar in higher and lower-acuity patients ( ie, patients in non-ICU settings or receiving low respiratory support), the confidence intervals were wider in lower-acuity patients. In addition, invasive ventilation was more commonly implemented during the early phase of the pandemic,28Hernandez-Romieu AC Adelman MW Hockstein MA et al.Timing of intubation and mortality among critically ill coronavirus disease 2019 patients: a single-center cohort study.Crit Care Med. 2020; 48: e1045-e1053Google Scholar and study sample sizes calculated on the basis of the intubation rate during the early pandemic can result in underpowered studies even after completion. Indeed, some of the studies were terminated early owing to the inability to recruit enough patients because of the declining COVID-19 pandemic ( NCT04853979).14Rosén J von Oelreich E Fors D et al.Awake prone positioning in patients with hypoxemic respiratory failure due to COVID-19: the PROFLO multicenter randomized clinical trial.Crit Care. 2021; 25: 209Google Scholar, 18Fralick M Colacci M Munshi L et al.Prone positioning of patients with moderate hypoxia due to COVID-19: a multicenter pragmatic randomized trial [ COVID PRONE ].medRxiv. 2021; ( published online Nov 8, 2021.) ( preprint).https: //doi.org/10.1101/2021.11.05.21264590Google Scholar, 19Garcia MA Rampon GL Doros G et al.Rationale and design of the awake prone position for early hypoxemia in COVID-19 ( APPEX-19) study protocol.Ann Am Thorac Soc. 2021; 18: 1560-1566Google Scholar Second, the finding that awake prone positioning resulted in a lower risk of intubation in patients with COVID-19 in an ICU setting but not for non-ICU patients could be explained by the higher ratio of health-care workers to patients in ICU. ICU patients might have more opportunities to receive encouragement or assistance to help them prone. However, even in ICU settings, patient adherence to awake prone positioning varied, with daily awake prone positioning duration ranging from 1–2 h/day to 8–10 h/day.11Ehrmann S Li J Ibarra-Estrada M et al.Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial.Lancet Respir Med. 2021; 9: 1387-1395Google Scholar Besides patient factors, clinician-driven awake prone positioning 29Ibarra-Estrada MA Marín-Rosales M García-Salcido R et al.Prone positioning in non-intubated patients with COVID-19 associated acute respiratory failure, the PRO-CARF trial: a structured summary of a study protocol for a randomised controlled trial.Trials. 2020; 21: 940Google Scholar rather than patient-driven awake prone positioning12Taylor SP Bundy H Smith WM Skavroneck S Taylor B Kowalkowski MA Awake-prone positioning strategy for non-intubated hypoxic patients with COVID-19: a pilot trial with embedded implementation evaluation.Ann Am Thorac Soc. 2021; 18: 1360-1368Google Scholar, 13Johnson SA Horton DJ Fuller MJ et al.Patient-directed prone positioning in awake patients with COVID-19 requiring hospitalization ( PAPR).Ann Am Thorac Soc. 2021; 18: 1424-1426Google Scholar, 17Gad S Awake prone positioning versus non invasive ventilation for COVID-19 patients with acute hypoxemic respiratory failure.Egypt J Anaesth. 2021; 37: 85-90Google Scholar, 18Fralick M Colacci M Munshi L et al.Prone positioning of patients with moderate hypoxia due to COVID-19: a multicenter pragmatic randomized trial [ COVID PRONE ].medRxiv. 2021; ( published online Nov 8, 2021.) ( preprint).https: //doi.org/10.1101/2021.11.05.21264590Google Scholar, 19Garcia MA Rampon GL Doros G et al.Rationale and design of the awake prone position for early hypoxemia in COVID-19 ( APPEX-19) study protocol.Ann Am Thorac Soc. 2021; 18: 1560-1566Google Scholar was probably the key to improving compliance with awake prone positioning. Third, the use of prone positioning in patients with advanced respiratory support might be associated with an increase in end-expiratory lung volume and a more homogeneous distribution in lung aeration,30Riera J Pérez P Cortés J Roca O Masclans JR Rello J Effect of high-flow nasal cannula and body position on end-expiratory lung volume: a cohort study using electrical impedance tomography.Respir Care. 2013; 58: 589-596Google Scholar potentially decreasing tidal hyperinflation of the ventral regions and promoting the recruitment of the dorsal regions of the lung, which leads to better ventilation–perfusion matching. Moreover, in intubated patients with ARDS, allowing spontaneous breathing during prone positioning improved gas exchange, decreased inspiratory effort and lung stress, and attenuated systemic inflammatory response.31Yoshida T Tanaka A Roldan R et al.Prone position reduces spontaneous inspiratory effort in patients with acute respiratory distress syndrome: a bicenter study.Am J Respir Crit Care Med. 2021; 203: 1437-1440Google Scholar These physiological benefits might have enabled some patients to stay in a prone position for a longer period; and a longer duration of awake prone positioning was found to be associated with treatment success.11Ehrmann S Li J Ibarra-Estrada M et al.Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial.Lancet Respir Med. 2021; 9: 1387-1395Google Scholar, 32Esperatti M Busico M Fuentes NA et al.Impact of exposure time in awake prone positioning on clinical outcomes of patients with COVID-19-related acute respiratory failure treated with high-flow nasal oxygen: a multicenter cohort study.Crit Care. 2022; 26: 16Google Scholar However, the results from the conventional oxygen therapy and non-ICU subgroups are inconclusive since the optimal information size was not reached. Therefore, further studies on these subpopulations are warranted.
No significant difference in mortality between awake prone positioning and the supine position was found in this meta-analysis, which might be attributed to the low power for mortality outcome, which was investigated as a secondary outcome in all the RCTs, and the short follow-up time of the studies ( most reported mortality as a 28-day outcome or as an in-hospital outcome). In contrast, mortality was found to be significantly reduced in observational studies, possibly due to the use of historical control groups or selection bias, including patients unable to prone in the control groups. Similar explanations apply to the absence of a difference between awake prone positioning and the supine position in the duration of ICU stay and duration of hospital stay, in addition to no difference between the two groups in escalation of respiratory support.
A strength of our meta-analysis is that we systematically reviewed the current literature on the basis of previous meta-analyses,10Pavlov I He H McNicholas B et al.Awake prone positioning in non-intubated patients with acute hypoxemic respiratory failure due to COVID-19: a systematic review of proportional outcomes comparing observational studies with and without awake prone positioning in the setting of COVID-19.Respir Care. 2022; 67: 102-114Google Scholar, 33Chua EX Zahir SMISM Ng KT et al.Effect of prone versus supine position in COVID-19 patients: a systematic review and meta-analysis.J Clin Anesth. 2021; 74110406Google Scholar, 34Cardona S Downing J Alfalasi R et al.Intubation rate of patients with hypoxia due to COVID-19 treated with awake proning: a meta-analysis.Am J Emerg Med. 2021; 43: 88-96Google Scholar, 35Ponnapa Reddy M Subramaniam A Afroz A et al.Prone positioning of nonintubated patients with coronavirus disease 2019—a systematic review and meta-analysis.Crit Care Med. 2021; 49: e1001-e1014Google Scholar which did not include any RCTs. Since 2021, several RCTs and meta-analyses have been published. Only two meta-analyses20Fazzini B Page A Pearse R Puthucheary Z Prone positioning for non-intubated spontaneously breathing patients with acute hypoxaemic respiratory failure: a systematic review and meta-analysis.Br J Anaes. 2022; 128: 352-362Google Scholar, 21Beran A Mhanna M Srour O et al.Effect of prone positioning on clinical outcomes of non-intubated subjects with COVID-19: A comparative systematic review and meta-analysis.Respiratory Care. Nov 2021; ( published online Nov 9, 2021.) https: //doi.org/10.4187/respcare.09362Google Scholar included RCTs, and one reported that awake prone positioning reduced mortality; 21Beran A Mhanna M Srour O et al.Effect of prone positioning on clinical outcomes of non-intubated subjects with COVID-19: A comparative systematic review and meta-analysis.Respiratory Care. Nov 2021; ( published online Nov 9, 2021.) https: //doi.org/10.4187/respcare.09362Google Scholar however, we suspect this benefit might have primarily been driven by observational data. Our analysis of observational studies also showed that awake prone positioning reduced mortality, confirming that this benefit is probably driven by observational data. To our knowledge, this is the first study that comprehensively includes all the published RCTs and observational studies of awake prone positioning with a control group. We separated the analysis of RCTs and observational studies, using observational studies as a sensitivity analysis. The results generated from the RCT analysis are convincing. Additionally, we contacted all the authors of RCTs with completed but unpublished studies for their aggregate data, with the aim of providing the strongest evidence on awake prone positioning to guide clinical practice in the ongoing pandemic.
There are several limitations in this study. First, the results are mainly driven by the three large sample size RCTs.11Ehrmann S Li J Ibarra-Estrada M et al.Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial.Lancet Respir Med. 2021; 9: 1387-1395Google Scholar, 18Fralick M Colacci M Munshi L et al.Prone positioning of patients with moderate hypoxia due to COVID-19: a multicenter pragmatic randomized trial [ COVID PRONE ].medRxiv. 2021; ( published online Nov 8, 2021.) ( preprint).https: //doi.org/10.1101/2021.11.05.21264590Google Scholar, 19Garcia MA Rampon GL Doros G et al.Rationale and design of the awake prone position for early hypoxemia in COVID-19 ( APPEX-19) study protocol.Ann Am Thorac Soc. 2021; 18: 1560-1566Google Scholar Second, only a few studies reported the actual awake prone positioning duration; and this value might not have been recorded very precisely since it was observed and recorded unsystematically and with unknown accuracy by bedside clinicians. Therefore, we were not able to assess the impact of awake prone positioning duration on patient outcome. Future studies need to find ways to accurately document the start and stop time for each position, including prone, lateral, and supine positions, and more efforts are required to improve patient adherence to awake prone positioning. Third, only patients with COVID-19 were included in this meta-analysis, thus the results might not be generalisable to non-COVID-related acute hypoxaemic respiratory failure. Confirmatory trials in patients with acute hypoxaemic respiratory failure unrelated to COVID-19 remain warranted.
In conclusion, this systematic review and meta-analysis found that in patients with COVID-19-related acute hypoxaemic respiratory failure, awake prone positioning reduced the need for intubation, particularly in those patients requiring advanced respiratory support and in those in the ICU setting at enrolment. The study did not demonstrate a benefit on mortality, the need for escalation of respiratory support, ICU admission, ICU length of stay, or hospital length of stay.
JLi, JGL, CG, and SE designed the meta-analysis project. Two independent groups of investigators ( JLi, WT, and JLu in one group; YP and IP in the other group) performed the literature search, screening, and data extraction. JLi, IP, SE, and CG contacted trialists for clarification on their data and invited researchers to provide unpublished data. MI-E, DV, AK, and BM participated in the resolution of discrepancies on data extraction. All the authors had full access to the data and JLi, JLu, YP, IP, WT, and ET verified the data. JLu and ET conducted data analysis. All authors significantly contributed to the conduct of the meta-analysis. JLi, JLu, YP, IP, WT, MI-E, DV, AK, BM, ET, JGL, CG, and SE attended bimonthly web meetings. JLi drafted the manuscript. All authors reviewed the manuscript for important intellectual content and approved the final manuscript. JLi, JLu, YP, IP, and WT contributed equally to the overall project described in this article. SE and JLi were responsible for the decision to submit the manuscript.
Data will be available for 36 months after Article publication for any purpose of analysis to researchers who provide a methodologically sound and ethically approved proposal.
SE discloses consultancy fees from Aerogen, research support from Aerogen and Fisher & Paykel Healthcare, and travel reimbursements from Aerogen and Fisher & Paykel Healthcare. JL discloses research funding from Fisher & Paykel Healthcare, Aerogen, and Rice Foundation, and speaker fees from American Association for Respiratory Care, Aerogen, Heyer, and Fisher & Paykel Healthcare. IP discloses a research grant and speaker fees from Fisher & Paykel Healthcare. YP discloses research support from Fisher & Paykel Healthcare. OR discloses a research grant from Hamilton Medical and speaker fees from Hamilton Medical, Ambu, Fisher & Paykel and Aerogen, and non-financial research support from Timpel and Masimo. DV discloses research funding from Teleflex Medical and Rice Foundation, and speaker fees from Theravance Biopharma. MT discloses consulting fees from Fisher & Paykel Healthcare. JRM discloses research support from Fisher & Paykel Healthcare, and speaker fees from Fisher & Paykel Healthcare, Gilead, Dextro and Linet. JGL discloses consulting fees from Baxter Healthcare and GlaxoSmithKline. KM is the primary investigator for the industry funded trial NCT03808922. MF is a consultant for a start-up company ( ProofDx) developing a CRISPR based diagnostic test for COVID-19. All other authors declare no competing interests.
The awake prone positioning Meta-analysis group thanks Ms Afsaneh Raissi from the Sinai Health System for her assistance in providing subgroup data from the COVID-PRONE trial, and Dr Stacy A Johnson, Dr Stephanie P Taylor, and Dr Devachandran Jayakumar for their helpful clarifications regarding their studies.
Download.pdf ( 4.27 MB) Help with pdf files Supplementary appendix
The pandemic and the great awakening in the management of acute hypoxaemic respiratory failureThe ability to provide invasive mechanical ventilation ( IMV) and high-quality, supportive intensive care was substantially limited during the peak of the pandemic because of the unprecedented demand for intensive care unit ( ICU) resources. As a result, clinicians turned towards less invasive and innovative approaches to manage patients with acute hypoxaemic respiratory failure. Techniques such as awake prone positioning of non-intubated patients, a seemingly simple approach that was largely only tested in observational studies before the pandemic, were used. Full-Text PDF | tech |
Oil’ s retreat pauses after shedding most of Russian war gains - News for the Energy Sector | Oil’ s retreat took a breather after giving up most of the gains following Russia’ s invasion of Ukraine, with attention turning to the prospect of reduced demand due to a Covid-19 resurgence in China.
Futures in New York climbed above $ 97 a barrel on Wednesday. Oil has tumbled into a bear market after losing more than 20% since closing at the highest level since 2008 just over a week ago. China, the world’ s biggest crude importer, has implemented several lockdowns across the country as it seeks to contain its worst coronavirus outbreak since the pandemic began.
Oil has experienced one of its most tumultuous trading periods ever as rapid developments around the war and the ensuing sanctions drove wild price fluctuations that pushed volatility to historic levels. There are still concerns that the disruptions to Russian crude flows will squeeze an already tight market, and the conflict is raging on despite efforts for a cease-fire.
“ The dominant feature in this market is volatility, ” said John Driscoll, a Singapore-based chief strategist at JTD Energy Services Pte. “ It’ s not really fundamentals at all, it’ s the geopolitics, the hysteria and the fear. This market is likely to rebound, but maybe not as aggressively. ”
Russia’ s invasion of Ukraine has roiled global commodity markets, driving up the prices of everything from fuels to metals and grains. OPEC took an unusual step in acknowledging that the war threatens to intensify the surge in global inflation in its monthly report on Tuesday. The International Energy Agency will provide its snapshot of the market later on Wednesday.
US President Joe Biden will travel to Brussels next week to meet with NATO allies. Russian President Vladimir Putin told European Council President Charles Michel that Ukraine “ is not showing a serious attitude toward finding mutually acceptable solutions ” in talks on ending the fighting, the Kremlin said.
Russian Foreign Minister Sergei Lavrov said sanctions on his country won’ t affect the Iranian nuclear deal, sparking optimism a deal could be reached that would allow the resumption of official oil flows from the OPEC producer.
West Texas Intermediate for April delivery rose 1.2% to $ 97.57 a barrel in New York Mercantile Exchange at 10:37 a.m. in Singapore after losing 6.4% on Tuesday. Brent for May settlement gained 1.6% to $ 101.48 on the ICE Futures Europe exchange after falling 6.5% on Tuesday. | general |
‘ No shortage of workers’ for North Sea jobs, say unions | Union leaders say they have not seen a ‘ candidate shortage’ for North Sea jobs, but that greater engagement with the workforce and better terms will help remove barriers.
A candidate shortage reported by some recruiters has not been seen in the union workforce, leaders have said.
As the oil price holds above $ 100 per barrel, some have pointed to a shortage of talent to meet the increasing levels of work being seen in the North Sea.
However, the claims were dismissed by offshore workers, many of whom said the problem lay with poor rates of pay, and a prevalence of zero-hour contracts with “ no job security ”.
Union leaders too, concurred with some of these assessments.
John Boland of Unite told Energy Voice: “ I am not aware of any major shortages in filling vacancies, although some trades like instrument and mechanical technicians have always been more difficult to fill. ”
According to trade body Offshore Energies UK ( OEUK), some 35,000 direct and indirect jobs in the North Sea energy sector were lost due to the Covid price shock.
Mr Boland continued: “ Numbers offshore are still below pre-Covid and many workers have left the industry, through redundancies or retiring, and these skills have been lost, and will be hard to replace. ”
Jake Molloy, regional organiser for RMT, was of a similar opinion.
“ There is no question that rates and conditions are having an impact on the industry’ s ability to attract workers. There is no shortage of workers that have been redundant, or are facing imminent redundancy, so the people and the skills are there, it’ s the nature of engagement which is the deterrent, ” he said.
Mr Molloy pointed to several key assets already being wound down or due for decommissioning, suggesting more offshore jobs may be lost in the near term. And for those looking to remain or re-enter the workforce, terms were unlikely to prove attractive.
“ The opportunities to remain in or get back into the industry are all too often through agencies or crewing agents. They are increasingly being offered as ‘ fixed term’ and often the offer of work involves being contracted in the “ IR35 ” engagement model, ” he explained.
While the impact of Covid has been clear however, GMB Scotland organiser Dom Pritchard said the North Sea jobs trends had been visible before the pandemic.
“ The pandemic has impacted the industry, but it’ s also exposed a race-to-the-bottom that’ s been happening for years. That’ s reflected in the fact an increasing number of tradespeople can achieve a greater work-life balance through employment on onshore construction projects like Hinkley Point C, where pay and conditions represent greater value for workers than they would offshore, ” he said.
Mr Boland said some recruitment issues may also be due to perceptions of the offshore industry, and in bringing new workforce members in.
“ We would always want higher rates and better terms and conditions for our members, but a big barrier to workers moving into and remaining in oil and gas industry is the perception it has a limited future, ” he added.
“ One problem is encouraging new people into the industry, and explaining that oil and gas will still be here for a number of years, and that there is a future in it and in renewables. ”
Another long-running issue for the unions and campaigners is the cost of certification, which is increasingly borne by workers themselves. Added Mr Molloy: “ Companies doing the hiring invariably insist on candidates having all the necessary certification in place. This is forcing many workers to self-sponsor themselves in the ‘ hope’ of securing work, an appalling failing for a sector so critical to society and the economy! ”
Mr Molloy said this was also behind the drive to create an “ offshore training passport ”, which would enable workers to more easily move between the oil and gas and renewables sectors.
The proposal appears to have support among the workforce. Writing on LinkedIn, one offshore construction manager commented: “ It can be solved tomorrow by increasing the rates, and getting some proper cross-industry dialogue on ‘ mandatory’ training – I can work west of Shetland in some of the worst weather and deepest water in Europe with a BOSIET, but can’ t work on a windfarm two miles off the coast of Norfolk doing exactly the same job. ”
Mr Boland agreed would go some way towards improving opportunities. “ But this is only one barrier, and there are other barriers that need also to be removed, such as wages and terms and conditions, ” he added.
Both representatives pointed to the Energy Services Agreement ( ESA), launched in March last year, as central to helping ensure fair and sustainable rates of pay for all offshore workers by setting minimum base rates and terms and conditions.
Mr Molloy noted this also prevents the market “ overheating ” – where rates of pay rise unsustainably, as was seen in the early 2010s.
Mr Boland said he believed the ESA model could also be used in the renewables sector, to remove another barrier, “ and make the whole energy sector a more attractive employer. ”
For Mr Pritchard and the GMB, the issue is of wider energy strategy. | general |
Why the world's happiest country ( and yours) should think more about people's well-being | The length of the border between Finland and Russia is 1,340 kilometers. Besides separating the European Union country from its neighbor, the border has also marked a grim reality: the largest happiness gap in Europe, with the happiest country alongside one of the unhappiest. Finland has received a lot of attention for taking the top spot in the World Happiness Report in recent years, but what does happiness really mean there and around the globe? For many years, researchers have measured well-being based on factors related to the economy, environment and unemployment statistics, but according to Frank Martela, university lecturer at Aalto University, we also need to look at factors that show how a country becomes—and remains—happy. `` Other countries outside of the Nordics, like Canada, New Zealand and Netherlands have started examining well-being more closely to better understand what factors explain why some citizens are happy and some not. well-being is very multi-layered. First, of course, you need to have your basic needs met. We might take food, shelter, and clean drinking water as self-evident, but if you suddenly lose them—like many civilians in Ukraine right now—life becomes a struggle. It's much easier to think about higher needs, such as self-expression, when you can take your survival relatively for granted, '' Martela explains. How happiness works Happiness seems to be a notion we universally value as humans—a consequence of human action that needs no further explanation. When you ask someone why they did something and their answer is `` it made me happy, '' that's typically enough of a reason. `` The international comparisons of national happiness typically focus on life satisfaction—they ask people, 'How satisfied are you with your life? '' ' Martela explains. `` Finland seems to excel here because of the Finnish welfare system's ability to help its citizens feel taken care of. Things like relatively generous unemployment benefits and nearly free healthcare help mitigate sources of unhappiness, ensuring that there are fewer people in Finland who are highly unsatisfied with their lives. '' Finland's ranking as the world's happiest country in 2018–2021 is from the World Happiness Report, which is based on surveys conducted in 160 different countries to gauge people's satisfaction. It asks the same question in each country: Think about your life on a scale from 0 to 10, with 0 being the worst possible life and 10 being the best. How would you rate your life on this scale? Similar surveys are also conducted by other organizations, like the European Union, which examines life satisfaction in all of its member countries. `` Research shows that high national ranking on these surveys is not so much about culture, '' Martela notes. `` It's more about how a country's institutions take care of their people—this leads to higher ratings of life satisfaction. '' This explains the stark gap between Finland and neighboring Russia seen recently in the happiness report. `` While well-functioning democracy and institutions, low corruption, and trust between people explain the high levels of happiness in Finland, it is exactly the absence of these factors that explain why Russians are so much less satisfied with their lives, '' says Martela. You are what you measure Since the coronavirus pandemic began, the Finnish Prime Minister's Office has been conducting a monthly survey to get fast and up-to-date information on the population's current attitudes and feelings. Recently, Martela collaborated with them to devise new questions examining current levels of well-being. `` Asking Finns to answer questions on a frequent, monthly basis is super important when measuring well-being. The pandemic is a good example of things happening fast—we had to catch up just as fast! We wouldn't get this data if we only measured markers once a year, '' Martela explains. `` It will be interesting to see what the survey reveals about how Finns have reacted to the war nearby. I am quite sure we will see increased stress and decreased optimism, but are there some demographic groups for whom the effects are especially strong? And who, as a result, would need more targeted help? Surveys like this can help to identify vulnerable groups within the population, so we can better support them. '' How frequently you survey a population can help policy-makers quickly see what's working and what's driving discontent, placing hope in the future of policy to address people's needs, and ultimately, their well-being. With the help of Martela and his colleagues, we're starting to see that asking questions about a population's well-being—and more specifically about how satisfied people are with their country's ability to take care of them—could be the ultimate ticket to tranquility. `` Instead of saying 'Finland is the happiest country in the world, ' perhaps a better statement is 'Finland is the country where people are least unhappy. ' When the institutions take care of citizens and ensure that their basic needs are met, they are more free to live the kind of life they want—allowing a sense of satisfaction and happiness to exist, '' says Martela. Explore further Pressure to feel good associated with poorer individual wellbeing in happier countries: study More information: 2022 World Happiness Report: worldhappiness.report/ Provided by Aalto University Citation: Why the world's happiest country ( and yours) should think more about people's well-being ( 2022, March 16) retrieved 17 March 2022 from https: //phys.org/news/2022-03-world-happiest-country-people-well-being.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.
Finland has received a lot of attention for taking the top spot in the World Happiness Report in recent years, but what does happiness really mean there and around the globe?
For many years, researchers have measured well-being based on factors related to the economy, environment and unemployment statistics, but according to Frank Martela, university lecturer at Aalto University, we also need to look at factors that show how a country becomes—and remains—happy.
`` Other countries outside of the Nordics, like Canada, New Zealand and Netherlands have started examining well-being more closely to better understand what factors explain why some citizens are happy and some not. well-being is very multi-layered. First, of course, you need to have your basic needs met. We might take food, shelter, and clean drinking water as self-evident, but if you suddenly lose them—like many civilians in Ukraine right now—life becomes a struggle. It's much easier to think about higher needs, such as self-expression, when you can take your survival relatively for granted, '' Martela explains.
How happiness works
Happiness seems to be a notion we universally value as humans—a consequence of human action that needs no further explanation. When you ask someone why they did something and their answer is `` it made me happy, '' that's typically enough of a reason.
`` The international comparisons of national happiness typically focus on life satisfaction—they ask people, 'How satisfied are you with your life? '' ' Martela explains. `` Finland seems to excel here because of the Finnish welfare system's ability to help its citizens feel taken care of. Things like relatively generous unemployment benefits and nearly free healthcare help mitigate sources of unhappiness, ensuring that there are fewer people in Finland who are highly unsatisfied with their lives. ''
Finland's ranking as the world's happiest country in 2018–2021 is from the World Happiness Report, which is based on surveys conducted in 160 different countries to gauge people's satisfaction. It asks the same question in each country: Think about your life on a scale from 0 to 10, with 0 being the worst possible life and 10 being the best. How would you rate your life on this scale? Similar surveys are also conducted by other organizations, like the European Union, which examines life satisfaction in all of its member countries.
`` Research shows that high national ranking on these surveys is not so much about culture, '' Martela notes. `` It's more about how a country's institutions take care of their people—this leads to higher ratings of life satisfaction. ''
This explains the stark gap between Finland and neighboring Russia seen recently in the happiness report. `` While well-functioning democracy and institutions, low corruption, and trust between people explain the high levels of happiness in Finland, it is exactly the absence of these factors that explain why Russians are so much less satisfied with their lives, '' says Martela.
You are what you measure
Since the coronavirus pandemic began, the Finnish Prime Minister's Office has been conducting a monthly survey to get fast and up-to-date information on the population's current attitudes and feelings. Recently, Martela collaborated with them to devise new questions examining current levels of well-being.
`` Asking Finns to answer questions on a frequent, monthly basis is super important when measuring well-being. The pandemic is a good example of things happening fast—we had to catch up just as fast! We wouldn't get this data if we only measured markers once a year, '' Martela explains.
`` It will be interesting to see what the survey reveals about how Finns have reacted to the war nearby. I am quite sure we will see increased stress and decreased optimism, but are there some demographic groups for whom the effects are especially strong? And who, as a result, would need more targeted help? Surveys like this can help to identify vulnerable groups within the population, so we can better support them. ''
How frequently you survey a population can help policy-makers quickly see what's working and what's driving discontent, placing hope in the future of policy to address people's needs, and ultimately, their well-being.
With the help of Martela and his colleagues, we're starting to see that asking questions about a population's well-being—and more specifically about how satisfied people are with their country's ability to take care of them—could be the ultimate ticket to tranquility.
`` Instead of saying 'Finland is the happiest country in the world, ' perhaps a better statement is 'Finland is the country where people are least unhappy. ' When the institutions take care of citizens and ensure that their basic needs are met, they are more free to live the kind of life they want—allowing a sense of satisfaction and happiness to exist, '' says Martela. Explore further Pressure to feel good associated with poorer individual wellbeing in happier countries: study More information: 2022 World Happiness Report: worldhappiness.report/ Provided by Aalto University Citation: Why the world's happiest country ( and yours) should think more about people's well-being ( 2022, March 16) retrieved 17 March 2022 from https: //phys.org/news/2022-03-world-happiest-country-people-well-being.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.
Explore further | tech |
Aaron Rodgers signs bumper contract extension with Green Bay Packers |
Aaron Rodgers
has signed a bumper contract extension with the
Green Bay Packers
.
The deal keeps the 38-year-old Rodgers, who recently was named the league's Most Valuable Player ( MVP) for the second straight year and the fourth time in his 17-year career, at the team he joined from college in 2005.
`` We are very pleased to be able to come to an agreement with Aaron that keeps him in Green Bay, '' Packers General Manager Brian Gutekunst told the
team's website
.
`` His play on the field and leadership in our locker room remain vital in our pursuit of another Super Bowl title. The agreement also allows us to maintain and enhance what we feel is already a very competitive roster. ''
The Packers did not disclose details of Rodgers ' deal, but he will earn over $ 150 million over the next three seasons, according to
the Spotrac website
.
Read More
Spotrac says Rodgers will earn $ 42 million in 2022, $ 59.5 million in 2023, and $ 49.3 million in 2024, with the 2025 and 2026 seasons as voidable years on the contract.
Aaron Rodgers throws the ball during the NFC Divisional Playoff game against the San Francisco 49ers at Lambeau Field on January 22, 2022.
Following the Packers ' loss to the San Francisco 49ers in the Divisional Playoff Round, it was unclear whether the 38-year-old would continue playing for the Packers, or even continue playing in the NFL.
Ultimately, however, he will return to the team that, as starting quarterback, he has guided to the playoffs 11 times in the last 14 seasons, eight division victories and one Super Bowl title.
In the process, Rodgers has gathered many individual accolades, including
four NFL MVPs
in 2011, 2014, 2020 and 2021 and a Superbowl MVP in 2010.
He finished the 2021 season throwing for 4,115 yards, 37 touchdowns and four interceptions, leading the Packers to the top seed in the National Football Conference.
In recent months, Rodgers ' off-the-field actions have landed him in the news. He and Shailene Woodley
ended their engagement
in February, one year after Woodley
announced the engagement to the public
during an interview with Jimmy Fallon.
Rodgers also made headlines for
his thoughts on Covid-19 vaccinations
. After admitting to testing positive in November, Rodgers missed the Week 9 matchup against the Kansas City Chiefs, which the Packers lost 13-7.
Aaron Rodgers claims his 'divisive ' vaccination status was the 'only reason ' people wanted Packers to lose in the playoffs
During an interview on `` The Pat McAfee Show '' that same month, Rodgers confirmed he was unvaccinated against Covid-19 and was disappointed with the treatment he was receiving in the media.
Visit CNN.com/sport for more news, features, and videos
Rodgers said the media was on a `` witch hunt '' to find out which players were vaccinated and blamed reporters for him saying he was `` immunized '' back in August.
Rodgers said if any reporter would have asked a follow-up question, he would have explained he's `` not an anti-vax flat earther, '' but that he's a `` critical thinker. ''
He did not get vaccinated because he has an allergy to an ingredient in the Moderna and Pfizer vaccines and was scared about the possible side effects from the Johnson & Johnson vaccine, he said.
The decision to seek alternative treatments was `` what was best for my body, '' he said.
In November,
the NFL issued fines
to the Packers, Rodgers and receiver Allen Lazard after its review found the team and its two players did not follow league Covid-19 protocols.
Scientists react to Aaron Rodgers ' comments on Covid-19 vaccine and treatments
The league determined Rodgers and Lazard each attended a Halloween party despite being unvaccinated, a violation of protocols prohibiting unvaccinated players from gathering outside of team facilities in a group of more than three players.
The NFL said while the team did not sanction the party, it was aware of the party after the fact and was being fined for failure to report the violations to the NFL and failure to discipline Rodgers and Lazard. | general |
Covid US: This key indicator may determine how bad a BA.2 wave could be |
With a
new version of the Omicron coronavirus variant
picking up steam in the United States, as many as 28 million seniors remain at risk of becoming severely ill from Covid-19, either because they are unvaccinated or partially vaccinated, or because it has been more than five months since their second or third dose of a vaccine, according to a CNN analysis of federal data.
As America casts a wary eye on rising cases caused by the BA.2 subvariant in Europe, the immune status of adults over the age of 65 will be a key indicator of how future variants will affect the US because the risk of severe outcomes rises dramatically with age.
What rising Covid-19 infections in the UK and Europe could mean for the US
`` It's really looking at that older age group and how much prior immunity they have, either from previous infection or vaccination, that I think has been the best indicator so far of how severe a given number of cases is going to end up being in terms of hospitalizations and deaths, '' said Stephen Kissler, who specializes in infectious disease modeling at Harvard's TH Chan School of Public Health.
An analysis
by the UK Health Security Agency shows that the BA.2 subvariant of Omicron is growing about 80% faster than BA.1, the virus that caused the last wave of infections in the US over the winter. Cases and hospitalizations are rising in the UK and several other European countries where BA.2 has become the dominant strain.
Even though head-to-head comparisons with BA.1 indicate that BA.2 is not more likely to lead to hospitalization, this variant has the potential to overwhelm health care resources in the US once again if it finds enough vulnerable people to infect.
Read More
Forgoing boosters
The most vulnerable group is adults over the age of 65, especially those who have little immunity against the virus. This is why Pfizer and BioNTech asked the US Food and Drug Administration this week to green-light fourth vaccine doses for older adults.
`` It's that group that's most problematic when it comes to the severe critical and fatal disease. It doesn't mean that younger folks don't wind up in the hospital at times; it's just not at the same rate, '' said Jeffrey Shaman, who specializes in modeling the spread of infectious diseases at Columbia University's Mailman School of Public Health.
Hong Kong bet on zero-Covid. Now it's facing a 'preventable disaster '
Shaman points to
Hong Kong
, which is in the throes of a severe wave caused by BA.2. It has the highest Covid-19 death rate in the world.
`` And they have not seen the full brunt of that because it lags a little bit, but it's because they have an elderly population that wasn't very well-vaccinated, '' he said.
US officials don't expect BA.2 to hit here as hard as it has in Hong Kong. That's because the city has pursued a zero-tolerance Covid strategy. That policy kept cases and deaths low up till now, making it a model for Covid control.
But Omicron and BA.2 have overwhelmed those defenses and started to infect a population with little prior exposure to the virus.
Hong Kong also relied on a slightly different mix of vaccines than the US and Europe, including the Chinese-made Sinovac shots and Pfizer's Comirnaty.
Dr. Sanjay Gupta: Is America ready to take the next step in its Covid-19 recovery?
Health officials are looking to the UK for clues to how BA.2 may behave in the US. But the they're not analogous in all ways; mostly notably, the UK is more highly vaccinated.
Overall, in the UK,
82% of adults
have had a third dose of a Covid-19 vaccine, something that is crucial to preventing infections and hospitalizations from Omicron because of how highly `` immune erosive '' these variants are, Shaman says. In the US, that
number is just 36%
.
Among Americans over the age of 65 who are eligible to get a booster,
CDC data
shows that 1 in 3 have not opted to get a third dose -- leaving about 15 million older Americans without that critical extra protection.
Protection wanes over time
Recent studies show that vaccine timing matters, too. Data collected by the UK's Health Security Agency shows that vaccine effectiveness against Omicron fell to 10% for infections, 35% of hospitalizations and 70% for deaths six months or more after the second dose.
Boosters restored much of that protection, but their benefits have faded, too. Four to six months after a third dose, boosters were about 40% to 50% effective at preventing Omicron infections and 75% to 85% at preventing hospitalizations, for all adults.
CDC estimates 140 million US Covid-19 infections
In the UK, about two-thirds of seniors have had a second, third or fourth dose of a Covid-19 vaccine within the past five months, but only about half of US seniors are within five months of their second or third vaccine dose.
Comparing antibody protection from a past Covid-19 infection or vaccination, the UK comes out ahead again. By the end of February, 98% of adults in the UK had tested positive for antibodies to Covid-19, according to the
Office of National Statistics
. In the US, the
CDC estimates
that 43% of Americans have antibodies from a past infection to fight off Covid-19. Seniors are the least likely to have this protection, however, with just 23% of adults over age 65 testing positive for antibodies from a previous infection.
`` I do still think it's a potential cause for concern that we may still see a higher case fatality rate and higher hospitalizations for Covid in the US than the UK because of the differences in underlying immunity, '' Kissler told CNN.
So while a BA.2 wave in the US may not be as severe as it is for Hong Kong, it might not be the same experience as the UK is having, either.
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`` What we see happening in the UK is going to be perhaps a better story than we should be expecting here, '' said Keri Althoff, an epidemiologist at the Johns Hopkins Bloomberg School of Public Health.
With perhaps a few critical weeks to prepare, Kissler and Shaman say vaccinations and boosters for seniors are an important place to start.
`` Every additional layer of protection that we get helps, and so I would highly recommend, especially somebody who's elderly who has yet gotten vaccinated to do so, because it really can go a long way towards giving you the durable and robust immunity that you want, '' Kissler said. `` This is definitely the time. ''
Clarification: This story has been updated to clarify that BA.2 is growing 80% faster than BA.1 in the United Kingdom. | general |
China boosts bed spaces as Omicron outbreak spreads | Hi, what are you looking for?
China has moved to free up hospital beds as officials reported thousands of new cases from an Omicron-led coronavirus outbreak.
By
Published
China has moved to free up hospital beds as officials on Wednesday reported thousands of new cases from an Omicron-led coronavirus outbreak that has put millions under lockdown and raised fears for the health system.
The country recorded 3,290 new Covid-19 cases on Wednesday, including 11 severe cases.
The total was down on Tuesday’ s count of more than 5,000, but the highly transmissible variant is posing the sternest challenge yet to China’ s ‘ zero-Covid’ strategy to contain the pandemic.
China, where the first virus case emerged in Wuhan in late 2019, has not officially reported any Covid-related deaths for more than a year.
Under strict Covid-19 protocols, the country previously sent all patients with any symptoms to specialist hospitals.
But a steep jump in cases, which has led to the 17.5 million residents of the southern tech hub of Shenzhen being locked down and restrictions imposed on Shanghai and other cities, has driven concerns over looming bed shortages.
The National Health Commission late Tuesday said patients with mild Covid cases could isolate at a central quarantine facility to ease pressure on hospitals.
“ Patients with Omicron variant strains are mainly asymptomatic infections and mild cases, most of them do not require serious treatment, ” the health authority said.
“ All admission to designated hospitals will take up a lot of medical resources. ”
Images of patients lying on gurneys outside hospitals in Hong Kong, where hospitals have been overrun by a surge in cases, have spooked mainland officials, who are now also rushing to build makeshift hospitals in some provinces.
Footage on state broadcaster CCTV Wednesday showed dozens of giant cranes assembling “ temporary hospitals ” in northeast China’ s Jilin province, which has reported more than 5,000 cases over the past week.
The province of more than 24 million residents has only 22,880 hospital beds.
As of Tuesday, 6,000 railway carriage-style hospital rooms — first erected during the early days of the pandemic in Wuhan — have been put in place in Jilin City and the nearby metropolis of Changchun, to deal with a feared influx of patients.
As well as leaving tens of millions of people under lockdown across the country, the latest spike in cases has sparked long queues outside mass testing sites and tight controls at ports, raising the risk of trade disruption.
With 2,400 staff representing 100 different nationalities, AFP covers the world as a leading global news agency. AFP provides fast, comprehensive and verified coverage of the issues affecting our daily lives.
Images of Ukrainian troops carrying Javelin missile launchers on their shoulders have flashed around the world.
North Korea conducted a missile test but the launch failed, Seoul said - Copyright AFP Jung Yeon-jeNorth Korea fired a projectile Wednesday but the...
Ukraine's besieged leader urged the U.S. to reconsider his plea for a no-fly zone, invoking the terror of the September 11 attacks.
The UN's top court on Wednesday ordered Russia to suspend its invasion of Ukraine.
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Pakistani truck artist gives new flair to kicks | Hi, what are you looking for?
Haider Ali dabs a brush with an iridescent glob of paint and gets to work on a pair of sparkling white trainers.
By
Published
Haider Ali dabs a brush with an iridescent glob of paint and gets to work on a pair of sparkling white trainers — his latest canvas for a carnival of colour celebrating Pakistani culture.
Pakistan’ s lorries are renowned for “ truck art ”: candy-coloured murals depicting South Asian animals, celebrities and religious icons.
The tradition transforms the highways and cities into kaleidoscopic processions.
And now Ali — a veteran truck artist — has transposed the painting onto sneakers.
“ A client came to me from the US asking me to paint shoes, ” he explained.
“ I told him an exorbitant fee to discourage him but he agreed, so I decided to get on with it. ”
He labours on each pair for up to four days, charging select clients $ 400 for a set featuring bespoke patterns and motifs.
Since he started painting trainers in January, he has dispatched eight pairs — to places in Pakistan and abroad — with new orders arriving every four days after a surge of social media interest.
“ The ideas keep coming to me, ” the 42-year-old mused.
“ It’ s in human nature to decorate ourselves and the things around us. ”
Cross-legged in his Karachi rooftop studio, he flips a pair of high-top Nikes to reveal the image of a luminous pink hawk and a gazing yellow eye, framed by hypnotic bulbous fringes.
Another pair ready for shipping bears a shimmering peacock.
– ‘ In the zone’ –
Some say the practice of adorning trucks began in the 1940s when hauliers crafted vibrant logos communicating their brand identity to a largely illiterate public.
Others claim the artistic one-upmanship began with bus drivers competing to lure passengers.
Today, the trade is one of Pakistan’ s most famous cultural exports, cutting against the country’ s more austere reputation for social conservatism.
Ali comes from a family of truck artists, who eked out a living at the roadside yards where drivers eagerly surrender slim pay packets to decorate their vehicles.
Strolling through the Yusuf Goth truck yard, his tinted glasses and slight swagger lend him an air of celebrity.
“ I get in the zone when I feel a connection to the art, ” he said. “ If I pause, the ideas stop flowing. ”
He came to fame outside Pakistan when his work was exhibited at the US Smithsonian Museum in 2002, helping him hone a reputation as an international ambassador for truck art.
He has applied his craft to a plane, a VW Beetle, and even a woman’ s body at the Burning Man festival in the United States.
Ali’ s cottage industry offers numerous advantages. He is stowed away from the din of the roadside yards, and his fashion clients give him full creative freedom, unlike truck drivers who peer over his shoulder.
But as with trucks, the decoration on shoes will not last forever.
After three or four years, it will chafe, crack and fade — offering a fresh canvas for yet more artwork.
With 2,400 staff representing 100 different nationalities, AFP covers the world as a leading global news agency. AFP provides fast, comprehensive and verified coverage of the issues affecting our daily lives.
Russia said Tuesday it would pull out of the Council of Europe after pressure mounted for Moscow to be expelled.
Images of Ukrainian troops carrying Javelin missile launchers on their shoulders have flashed around the world.
A cameraman for Fox News, Pierre Zakrzewski, has been killed in Ukraine outside Kyiv, the US network said Tuesday.
China has moved to free up hospital beds as officials reported thousands of new cases from an Omicron-led coronavirus outbreak.
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7.3-magnitude quake hits east Japan, tsunami advisory issued | Hi, what are you looking for?
By
Published
A powerful 7.3-magnitude quake jolted east Japan on Wednesday night, rattling the capital Tokyo and prompting a tsunami advisory for parts of the northeast coast, the Japan Meteorological Agency said.
The quake was centred off the coast of the Fukushima region at a depth of 60 kilometres ( 37 miles).
Shortly after it hit at 11:36 pm ( 1436 GMT) an advisory for tsunami waves of one metre was issued for parts of the coast.
There were no immediate reports of damage or injuries, but at least two million households were left without power in the central Kanto region, including 700,000 in Tokyo, electricity provider TEPCO said.
In the northeast, 156,000 households had no power, regional energy company Tohoku Electric Power said.
Prime Minister Fumio Kishida told reporters the government was gathering information on the situation.
“ We will commit ourselves to gathering information, do our best to rescue those affected by the ( quake) and communicate information appropriately, ” he said.
TEPCO also said in a tweet that it was checking operations at the Fukushima nuclear plant that went into meltdown 11 years ago after a huge 9.0-magnitude quake hit off the eastern coast on March 11, 2011, triggering a tsunami and nuclear disaster.
The nuclear regulation authority said there were no abnormalities detected at Onagawa nuclear plant in the northeastern Miyagi prefecture.
– Ring of Fire –
Regional train company JR East said it was experiencing significant disruption to its operations.
Japan sits on the Pacific “ Ring of Fire ”, an arc of intense seismic activity that stretches through Southeast Asia and across the Pacific basin.
The country is regularly hit by quakes, and has strict construction regulations intended to ensure buildings can withstand strong tremors.
But it remains haunted by the memory of the 2011 undersea quake in northeastern Japan that triggered a deadly tsunami and unleashed the Fukushima nuclear accident.
A minute’ s silence was held on Friday, the anniversary of the disaster, to remember the some 18,500 people left dead or missing in the tsunami.
Around the stricken Fukushima plant, extensive decontamination has been carried out, and this year five former residents of Futaba, the region’ s last uninhabited town, returned to live there on a trial basis.
Around 12 percent of Fukushima was once declared unsafe but no-go zones now cover just 2.4 percent of the prefecture, although populations in many towns remain far lower than before.
With 2,400 staff representing 100 different nationalities, AFP covers the world as a leading global news agency. AFP provides fast, comprehensive and verified coverage of the issues affecting our daily lives.
Russia said Tuesday it would pull out of the Council of Europe after pressure mounted for Moscow to be expelled.
Images of Ukrainian troops carrying Javelin missile launchers on their shoulders have flashed around the world.
A cameraman for Fox News, Pierre Zakrzewski, has been killed in Ukraine outside Kyiv, the US network said Tuesday.
China has moved to free up hospital beds as officials reported thousands of new cases from an Omicron-led coronavirus outbreak.
COPYRIGHT © 1998 - 2022 DIGITAL JOURNAL INC. Digital Journal is not responsible for the content of external sites. Read more about our external linking. | general |
'Stealth ' omicron cases rising in the US: Here's what we know. | Live Science is supported by its audience. When you purchase through links on our site, we may earn an affiliate commission. Learn more
By Nicoletta Lanese published 16 March 22
Here's what we know about BA.2 in the U.S.
The omicron subvariant BA.2, also known as `` stealth '' omicron, has steadily grown more common in the U.S. since it was first detected in the country in January, but that doesn't mean it will trigger a huge new wave of infection. That said, some experts are still concerned that such a surge could occur.
Here's what you should know about the rise of stealth omicron in the U.S.:
Scientists first identified the subvariant back in December 2021, Live Science previously reported. At that time, they discovered that the original omicron lineage had split in two. They designated the original version of the variant as BA.1 and its genetically distinct spin-off as BA.2.
( Later, another sublineage was identified and named BA.3, and BA.1 spawned another sublineage known as BA.1.1, according to NewsMedical. BA.1.1 very closely resembles the original omicron but carries a substitution in the gene that codes for its spike protein.)
BA.2 became known as `` stealth '' omicron because researchers raised concerns that the subvariant might be more difficult to track than the original omicron variant.
Related: Coronavirus variants: Facts about omicron, delta and other COVID-19 mutants
Unlike stealth omicron, BA.1 bears a deletion in the gene that codes for its spike protein, which the virus uses to infect cells. This specific mutation causes PCR tests to display an error message — `` S gene target failure '' — when they detect the original omicron, and this error message made the omicron variant easy to track when it first emerged, Live Science reported. This error message did not affect the ability of PCR tests to detect a COVID-19 infection, because the tests scan for multiple coronavirus genes.
BA.2 doesn't have this mutation, so it doesn't generate the same error message. That meant that, at least on PCR tests, stealth omicron looks similar to the delta variant or other coronavirus variants without the spike mutation. So, to correctly identify a stealth omicron case when there were several variants circulating, scientists would need to complete a full genomic analysis.
Now, however, omicron subvariants account for the vast majority of new cases worldwide. With little to no cases caused by delta or other variants, the so-called stealth variant should now be easy to spot, The New York Times reported.
BA.2 was detected at low levels in the U.S. in January, Live Science previously reported, but cases have ticked upward since then. Between Jan. 30 and Feb. 5, the subvariant accounted for about 1% of the new coronavirus cases captured by the Centers for Disease Control and Prevention's ( CDC) national genomic surveillance system, the agency reported. That number jumped to about 7% toward the end of February and then up to nearly 14% in the first week of March, the CDC estimated.
Between March 6 and March 12, BA.2 accounted for an estimated 23.1% of new coronavirus cases in the country, the CDC reported. In the same week, BA.1 accounted for 10.8% of cases, and BA.1.1 made up the other 66.1%.
So, as of mid-March, BA.2 cases continue to grow more common in the U.S., but they 've yet to edge out cases caused by other versions of omicron. By contrast, in other countries — including the Philippines, India, Denmark, Singapore, Austria and South Africa — BA.2 quickly outpaced BA.1 and had become the dominant subvariant by January, NewsMedical reported.
Related: 20 of the worst epidemics and pandemics in history
BA.2 may follow the same trajectory in the U.S. and soon emerge as the dominant subvariant. But if it takes over, will the subvariant trigger a massive new wave of infection? Not necessarily, the Times reported.
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That's partially because, although BA.2 seems to spread more easily than the original omicron, previous infections with BA.1 seem to provide strong protection against infection with BA.2, `` at least for the limited period for which data are available, '' according to a Feb. 22 statement from the World Health Organization ( WHO).
Vaccines seem to offer similar levels of protection against both subvariants, although in general, all versions of omicron can cause breakthrough infections, the Times reported. The vaccines still offer strong protection against severe disease and hospitalization from omicron, and booster shots strengthen that protection, data from the U.K. government suggest.
However, some experts are still wary of a potential surge driven by BA.2. Although millions of U.S. residents caught omicron during the recent winter wave and may now be protected from BA.2, it's unclear how long that protection lasts, Jeffrey Shaman, an epidemiologist at the Columbia University Mailman School of Public Health, told The Washington Post. The relaxation of mask mandates and other precautions could also hasten BA.2's spread, while variable vaccination rates around the country could lead to hotspots of severe disease and hospitalization, should a surge occur, the Post reported.
Preliminary data from the U.K. hint that BA.2 isn't more likely to cause severe disease and hospitalization compared with BA.1, but this finding still needs to be confirmed. A recent study in hamsters suggested that the stealth variant does trigger more severe disease than BA.1, but it's not clear whether these findings in hamsters would carry over to humans, the Times reported.
For now, BA.2 appears to be spreading more slowly in the U.S. than it has in other countries, for reasons that aren’ t entirely clear, Debbie Dowell, chief medical officer for the CDC’ s covid-19 response, said in a briefing Saturday ( March 12) for clinicians sponsored by the Infectious Diseases Society of America, the Washington Post reported.
`` The speculation I 've seen is that it may extend the curve going down, case rates from omicron, but is unlikely to cause another surge that we saw initially with omicron, '' Dowell said.
Originally published on Live Science. | general |
Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron ( B.1.1.529) and delta ( B.1.617.2) variants in England: a cohort study | BackgroundThe omicron variant ( B.1.1.529) of SARS-CoV-2 has demonstrated partial vaccine escape and high transmissibility, with early studies indicating lower severity of infection than that of the delta variant ( B.1.617.2). We aimed to better characterise omicron severity relative to delta by assessing the relative risk of hospital attendance, hospital admission, or death in a large national cohort.MethodsIndividual-level data on laboratory-confirmed COVID-19 cases resident in England between Nov 29, 2021, and Jan 9, 2022, were linked to routine datasets on vaccination status, hospital attendance and admission, and mortality. The relative risk of hospital attendance or admission within 14 days, or death within 28 days after confirmed infection, was estimated using proportional hazards regression. Analyses were stratified by test date, 10-year age band, ethnicity, residential region, and vaccination status, and were further adjusted for sex, index of multiple deprivation decile, evidence of a previous infection, and year of age within each age band. A secondary analysis estimated variant-specific and vaccine-specific vaccine effectiveness and the intrinsic relative severity of omicron infection compared with delta ( ie, the relative risk in unvaccinated cases).FindingsThe adjusted hazard ratio ( HR) of hospital attendance ( not necessarily resulting in admission) with omicron compared with delta was 0·56 ( 95% CI 0·54–0·58); for hospital admission and death, HR estimates were 0·41 ( 0·39–0·43) and 0·31 ( 0·26–0·37), respectively. Omicron versus delta HR estimates varied with age for all endpoints examined. The adjusted HR for hospital admission was 1·10 ( 0·85–1·42) in those younger than 10 years, decreasing to 0·25 ( 0·21–0·30) in 60–69-year-olds, and then increasing to 0·47 ( 0·40–0·56) in those aged at least 80 years. For both variants, past infection gave some protection against death both in vaccinated ( HR 0·47 [ 0·32–0·68 ]) and unvaccinated ( 0·18 [ 0·06–0·57 ]) cases. In vaccinated cases, past infection offered no additional protection against hospital admission beyond that provided by vaccination ( HR 0·96 [ 0·88–1·04 ]); however, for unvaccinated cases, past infection gave moderate protection ( HR 0·55 [ 0·48–0·63 ]). Omicron versus delta HR estimates were lower for hospital admission ( 0·30 [ 0·28–0·32 ]) in unvaccinated cases than the corresponding HR estimated for all cases in the primary analysis. Booster vaccination with an mRNA vaccine was highly protective against hospitalisation and death in omicron cases ( HR for hospital admission 8–11 weeks post-booster vs unvaccinated: 0·22 [ 0·20–0·24 ]), with the protection afforded after a booster not being affected by the vaccine used for doses 1 and 2.InterpretationThe risk of severe outcomes following SARS-CoV-2 infection is substantially lower for omicron than for delta, with higher reductions for more severe endpoints and significant variation with age. Underlying the observed risks is a larger reduction in intrinsic severity ( in unvaccinated individuals) counterbalanced by a reduction in vaccine effectiveness. Documented previous SARS-CoV-2 infection offered some protection against hospitalisation and high protection against death in unvaccinated individuals, but only offered additional protection in vaccinated individuals for the death endpoint. Booster vaccination with mRNA vaccines maintains over 70% protection against hospitalisation and death in breakthrough confirmed omicron infections.FundingMedical Research Council, UK Research and Innovation, Department of Health and Social Care, National Institute for Health Research, Community Jameel, and Engineering and Physical Sciences Research Council.
The omicron variant ( B.1.1.529) of SARS-CoV-2 has demonstrated partial vaccine escape and high transmissibility, with early studies indicating lower severity of infection than that of the delta variant ( B.1.617.2). We aimed to better characterise omicron severity relative to delta by assessing the relative risk of hospital attendance, hospital admission, or death in a large national cohort.
Individual-level data on laboratory-confirmed COVID-19 cases resident in England between Nov 29, 2021, and Jan 9, 2022, were linked to routine datasets on vaccination status, hospital attendance and admission, and mortality. The relative risk of hospital attendance or admission within 14 days, or death within 28 days after confirmed infection, was estimated using proportional hazards regression. Analyses were stratified by test date, 10-year age band, ethnicity, residential region, and vaccination status, and were further adjusted for sex, index of multiple deprivation decile, evidence of a previous infection, and year of age within each age band. A secondary analysis estimated variant-specific and vaccine-specific vaccine effectiveness and the intrinsic relative severity of omicron infection compared with delta ( ie, the relative risk in unvaccinated cases).
The adjusted hazard ratio ( HR) of hospital attendance ( not necessarily resulting in admission) with omicron compared with delta was 0·56 ( 95% CI 0·54–0·58); for hospital admission and death, HR estimates were 0·41 ( 0·39–0·43) and 0·31 ( 0·26–0·37), respectively. Omicron versus delta HR estimates varied with age for all endpoints examined. The adjusted HR for hospital admission was 1·10 ( 0·85–1·42) in those younger than 10 years, decreasing to 0·25 ( 0·21–0·30) in 60–69-year-olds, and then increasing to 0·47 ( 0·40–0·56) in those aged at least 80 years. For both variants, past infection gave some protection against death both in vaccinated ( HR 0·47 [ 0·32–0·68 ]) and unvaccinated ( 0·18 [ 0·06–0·57 ]) cases. In vaccinated cases, past infection offered no additional protection against hospital admission beyond that provided by vaccination ( HR 0·96 [ 0·88–1·04 ]); however, for unvaccinated cases, past infection gave moderate protection ( HR 0·55 [ 0·48–0·63 ]). Omicron versus delta HR estimates were lower for hospital admission ( 0·30 [ 0·28–0·32 ]) in unvaccinated cases than the corresponding HR estimated for all cases in the primary analysis. Booster vaccination with an mRNA vaccine was highly protective against hospitalisation and death in omicron cases ( HR for hospital admission 8–11 weeks post-booster vs unvaccinated: 0·22 [ 0·20–0·24 ]), with the protection afforded after a booster not being affected by the vaccine used for doses 1 and 2.
The risk of severe outcomes following SARS-CoV-2 infection is substantially lower for omicron than for delta, with higher reductions for more severe endpoints and significant variation with age. Underlying the observed risks is a larger reduction in intrinsic severity ( in unvaccinated individuals) counterbalanced by a reduction in vaccine effectiveness. Documented previous SARS-CoV-2 infection offered some protection against hospitalisation and high protection against death in unvaccinated individuals, but only offered additional protection in vaccinated individuals for the death endpoint. Booster vaccination with mRNA vaccines maintains over 70% protection against hospitalisation and death in breakthrough confirmed omicron infections.
Medical Research Council, UK Research and Innovation, Department of Health and Social Care, National Institute for Health Research, Community Jameel, and Engineering and Physical Sciences Research Council.
During the COVID-19 pandemic, multiple variants of SARS-CoV-2 have emerged that have been found to vary in transmissibility and severity. The omicron ( B.1.1.529) variant was first detected in a sample collected in Botswana on Nov 11, 2021 and first reported by South Africa on Nov 24, 2021.1WHOClassification of omicron ( B.1.1.529): SARS-CoV-2 variant of concern.https: //www.who.int/news/item/26-11-2021-classification-of-omicron- ( b.1.1.529) -sars-cov-2-variant-of-concernDate: Nov 26, 2021Date accessed: March 9, 2022Google Scholar, 2Centers for Disease Control and PreventionScience brief: omicron ( B.1.1.529) variant.https: //www.cdc.gov/coronavirus/2019-ncov/science/science-briefs/scientific-brief-omicron-variant.htmlDate accessed: March 9, 2022Google Scholar Omicron was designated a variant of concern by WHO on Nov 26, 2021.1WHOClassification of omicron ( B.1.1.529): SARS-CoV-2 variant of concern.https: //www.who.int/news/item/26-11-2021-classification-of-omicron- ( b.1.1.529) -sars-cov-2-variant-of-concernDate: Nov 26, 2021Date accessed: March 9, 2022Google Scholar To date, this variant has been identified in 133 countries and is now the most prevalent lineage globally, representing 85% of variant cases reported in late January, 2022.3GISAIDTracking of variants.https: //www.gisaid.org/hcov19-variants/Date accessed: March 9, 2022Google Scholar Delta ( B.1.617.2) was the dominant variant in England between May and December, 2021. The first omicron case in England was reported on Nov 27, 2021, at a time when daily case numbers by specimen date had been 30 000–50 000 per day since July, 2021, and incidence of infection was estimated to be 40 000–80 000 per day over the same months.4Birrell P Blake J van Leeuwen E De Angelis D MRC Biostatistics Unit COVID-19 Working GroupReport on nowcasting and forecasting.https: //www.mrc-bsu.cam.ac.uk/now-casting/report-on-nowcasting-and-forecasting-9th-december-2021/Date: Dec 9, 2021Date accessed: March 9, 2022Google Scholar Since then, the number of confirmed omicron cases has rapidly increased in England; by the week commencing Jan 10, 2022, omicron cases represented more than 99% of all sequenced cases.5UK Health Security AgencySARS-CoV-2 variants of concern and variants under investigation in England: technical briefing 35.https: //assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment data/file/1050999/Technical-Briefing-35-28January2022.pdfDate: 2022Date accessed: March 9, 2022Google Scholar
Research in contextEvidence before this studyWe aimed to identify all available evidence on the relative severity of omicron compared with other SARS-CoV-2 variants. On Jan 29, 2022, we searched PubMed with the query ( ( “ B.1.1.529 ” OR “ omicron ” OR “ VOC-21NOV-01 ”) AND ( “ SARS-CoV-2 ” OR “ COVID-19 ” OR “ severe acute respiratory syndrome coronavirus 2 ” OR “ coronavirus disease 2019 ”)) AND ( “ severity ” OR “ hospitalisation ” OR “ hospitalization ” OR “ hospital ” OR “ emergency care ” OR “ mortality ” OR “ lethality ” OR “ death ”), with no date or language restrictions. We further searched the medRxiv and SSRN preprint databases using combinations of the above search terms and included additional relevant literature from the reference lists of identified publications. This search identified three peer-reviewed publications and eight preprints. Comparing omicron with delta cases across all ages, published estimates of the reduction in the risk of hospitalisation or emergency department attendance ranged from 35% to 80%, with higher reductions in risk generally being reported for more severe outcomes, such as intensive care unit admission and death. A Norwegian cohort study reported age-stratified relative risk estimates and reported no differences with age for people younger than 75 years, but had insufficient power to disaggregate the younger than 30 years age group. Conversely, a Danish cohort study reported a relative risk of hospitalisation of 0·64 overall, but 1·59 in 0–19-year-olds, but again had insufficient power to disaggregate further. A US cohort study of children younger than 5 years reported relative risks of emergency department attendance and intensive care unit admission of 0·71 and 0·32, respectively.Added value of this studyTo date, this is the largest national study quantifying the risk of hospitalisation or death after infection with omicron compared with delta, based on individual-level data on 1 516 702 COVID-19 cases, of whom 1 067 859 were infected with the omicron variant. We provide age-specific estimates of the risk of hospitalisation and death for omicron relative to delta, and the disaggregation of the reduction in the risk of hospitalisation into estimates of the intrinsic severity reduction in unvaccinated cases and changes in vaccine-induced protection against hospitalisation in breakthrough cases. Furthermore, we estimate the additional protection provided by previous infection for unvaccinated and vaccinated individuals.Implications of all the available evidenceThe overall risk of severe outcomes for omicron infection is substantially lower than that for delta. However, this reduction in risk is age-specific and our results indicate that the risk of hospitalisation among children younger than 10 years does not significantly differ between omicron and delta. The reduction in the risk of hospitalisation observed at the population level is composed of a larger reduction in intrinsic severity coupled with a moderate reduction in the protection afforded by vaccination against hospitalisation.
We aimed to identify all available evidence on the relative severity of omicron compared with other SARS-CoV-2 variants. On Jan 29, 2022, we searched PubMed with the query ( ( “ B.1.1.529 ” OR “ omicron ” OR “ VOC-21NOV-01 ”) AND ( “ SARS-CoV-2 ” OR “ COVID-19 ” OR “ severe acute respiratory syndrome coronavirus 2 ” OR “ coronavirus disease 2019 ”)) AND ( “ severity ” OR “ hospitalisation ” OR “ hospitalization ” OR “ hospital ” OR “ emergency care ” OR “ mortality ” OR “ lethality ” OR “ death ”), with no date or language restrictions. We further searched the medRxiv and SSRN preprint databases using combinations of the above search terms and included additional relevant literature from the reference lists of identified publications. This search identified three peer-reviewed publications and eight preprints. Comparing omicron with delta cases across all ages, published estimates of the reduction in the risk of hospitalisation or emergency department attendance ranged from 35% to 80%, with higher reductions in risk generally being reported for more severe outcomes, such as intensive care unit admission and death. A Norwegian cohort study reported age-stratified relative risk estimates and reported no differences with age for people younger than 75 years, but had insufficient power to disaggregate the younger than 30 years age group. Conversely, a Danish cohort study reported a relative risk of hospitalisation of 0·64 overall, but 1·59 in 0–19-year-olds, but again had insufficient power to disaggregate further. A US cohort study of children younger than 5 years reported relative risks of emergency department attendance and intensive care unit admission of 0·71 and 0·32, respectively.
To date, this is the largest national study quantifying the risk of hospitalisation or death after infection with omicron compared with delta, based on individual-level data on 1 516 702 COVID-19 cases, of whom 1 067 859 were infected with the omicron variant. We provide age-specific estimates of the risk of hospitalisation and death for omicron relative to delta, and the disaggregation of the reduction in the risk of hospitalisation into estimates of the intrinsic severity reduction in unvaccinated cases and changes in vaccine-induced protection against hospitalisation in breakthrough cases. Furthermore, we estimate the additional protection provided by previous infection for unvaccinated and vaccinated individuals.
The overall risk of severe outcomes for omicron infection is substantially lower than that for delta. However, this reduction in risk is age-specific and our results indicate that the risk of hospitalisation among children younger than 10 years does not significantly differ between omicron and delta. The reduction in the risk of hospitalisation observed at the population level is composed of a larger reduction in intrinsic severity coupled with a moderate reduction in the protection afforded by vaccination against hospitalisation.
A number of studies have indicated that the clinical severity of infection is lower for omicron than for delta.6Wolter N Jassat W Walaza S et al.Early assessment of the clinical severity of the SARS-CoV-2 omicron variant in South Africa: a data linkage study.Lancet. 2022; 399: 437-446Google Scholar, 7Sheikh A Kerr S Woolhouse M McMenamin J Robertson C Severity of omicron variant of concern and vaccine effectiveness against symptomatic disease: national cohort with nested test negative design study in Scotland. University of Edinburgh, 2021https: //www.research.ed.ac.uk/en/publications/severity-of-omicron-variant-of-concern-and-vaccine-effectiveness-Date accessed: March 9, 2022Google Scholar, 8Ferguson N Ghani A Hinsley W Volz E Report 50: hospitalisation risk for omicron cases in England.https: //www.imperial.ac.uk/mrc-global-infectious-disease-analysis/covid-19/report-50-severity-omicron/Date: 2021Date accessed: March 9, 2022Google Scholar, 9Ulloa AC Buchan SA Daneman N Brown KA Estimates of SARS-CoV-2 omicron variant severity in Ontario, Canada.JAMA. 2022; ( published online Feb 17.) https: //doi.org/10.1101/jama.2022.2274Google Scholar, 10Lewnard JA Hong VX Patel MM Kahn R Lipsitch M Tartof SY Clinical outcomes among patients infected with omicron ( B.1.1.529) SARS-CoV-2 variant in southern California.medRxiv. 2022; ( published online Jan 11.) ( preprint).https: //doi.org/10.1101/2022.01.11.22269045Google Scholar, 11Bager P Wohlfahrt J Bhatt S et al.Reduced risk of hospitalisation associated with infection with SARS-CoV-2 omicron relative to delta: a Danish cohort study.SSRN. 2022; ( published online Jan 14, 2022.) ( preprint).https: //dx.doi.org/10.2139/ssrn.4008930Google Scholar, 12Wang L Berger NA Kaelber DC Davis PB Volkow ND Xu R COVID infection severity in children under 5 years old before and after omicron emergence in the US.medRxiv. 2022; ( published online Jan 13.) ( preprint).https: //doi.org/10.1101/2022.01.12.22269179Google Scholar, 13Veneti L Bøås H Bråthen Kristoffersen A et al.Reduced risk of hospitalisation among reported COVID-19 cases infected with the SARS-CoV-2 omicron BA.1 variant compared with the delta variant, Norway, December 2021 to January 2022.Eurosurveillance. 2022; 272200077Google Scholar, 14Abdullah F Myers J Basu D et al.Decreased severity of disease during the first global omicron variant covid-19 outbreak in a large hospital in Tshwane, South Africa.Int J Infect Dis. 2022; 116: 38-42Google Scholar, 15Peralta-Santos A Rodrigues EF Moreno J et al.Omicron ( BA.1) SARS-CoV-2 variant is associated with reduced risk of hospitalization and length of stay compared with delta ( B.1.617.2).medRxiv. 2022; ( published online Jan 25.) ( preprint).https: //doi.org/10.1101/2022.01.20.22269406Google Scholar, 16Jassat W Abdool Karim SS Mudara C et al.Clinical severity of COVID-19 patients admitted to hospitals in Gauteng, South Africa during the omicron-dominant fourth wave.SSRN. 2021; ( published online Dec 29.) ( preprint).https: //dx.doi.org/10.2139/ssrn.3996320Google Scholar, 17Davies M-A Kassanjee R Rosseau P et al.Outcomes of laboratory-confirmed SARS-CoV-2 infection in the omicron-driven fourth wave compared with previous waves in the Western Cape Province, South Africa.medRxiv. 2022; ( published online Jan 12.) ( preprint).https: //doi.org/10.1101/2022.01.12.22269148Google Scholar Vaccine effectiveness estimates show reduced protection against symptomatic infection for omicron compared with that of delta, with this protection being low after the primary course, but moderate against symptomatic infection and high against hospitalisation after a booster dose.18Andrews N Stowe J Kiresbom F et al.Effectiveness of COVID-19 vaccines against the omicron ( B.1.1.529) variant of concern.NEJM. 2022; ( published online March 2.) https: //dx.doi.org/10.1056/NEJMoa2119451Google Scholar In England, such estimates have been obtained in a context of high vaccination coverage. By Jan 9, 2022, more than 95% of people in England aged over 70 years had received one vaccine dose, more than 93% had received two vaccine doses, and more than 90% had received three vaccine doses.19UK Health Security AgencyCOVID-19 vaccine surveillance report: week 6.https: //assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment data/file/1054071/vaccine-surveillance-report-week-6.pdfDate: 2022Date accessed: March 9, 2022Google Scholar Coverage, notably of boosters, was lower in younger age groups, with 81%, 52%, and 43% having received three doses in the 55–59 years, 40–44 years, and 30–34 years age groups, respectively.19UK Health Security AgencyCOVID-19 vaccine surveillance report: week 6.https: //assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment data/file/1054071/vaccine-surveillance-report-week-6.pdfDate: 2022Date accessed: March 9, 2022Google Scholar
However, a detailed understanding is needed of how reductions in both severity and immunity have shaped observed patterns of hospitalisations and deaths in the omicron wave, and there has been scarce characterisation of age variation in the severity of omicron infection to date. To inform the public health response, we aimed to assess the relative risks of hospitalisation and death by age for infection with omicron versus delta. We also sought to estimate how immunity from both vaccination and past infection modifies disease severity in breakthrough cases.
COVID-19 is a notifiable disease and data for all positive cases in England are reported to the UK Health Security Agency ( UKHSA), which maintains a definitive line list of all individuals who have had confirmed SARS-CoV-2 infection.20Clare T Twohig KA O'Connell AM Dabrera G Timeliness and completeness of laboratory-based surveillance of COVID-19 cases in England.Public Health. 2021; 194: 163-166Google Scholar UKHSA also maintains separate line lists of COVID-19-associated deaths, reinfection episodes, S-gene target failure data, and sequencing and genotyping test results. The UK sequencing and genotyping strategy has been previously described.21Twohig KA Nyberg T Zaidi A et al.Hospital admission and emergency care attendance risk for SARS-CoV-2 delta ( B.1.617.2) compared with alpha ( B.1·1.7) variants of concern: a cohort study.Lancet Infect Dis. 2021; 22: 35-42Google Scholar, 22UK Health Security AgencySARS-CoV-2 variant data update, England: Version 21.https: //www.gov.uk/government/publications/investigation-of-sars-cov-2-variants-routine-variant-data-updateDate: 2022Date accessed: March 9, 2022Google Scholar Briefly, this strategy includes geographically weighted, population-level sampling of community cases, supplemented by targeted sampling of recent international travellers, hospitalised cases, and hospital staff. Over the study period, 6–20% of cases were sequenced, and 16–35% of cases were either sequenced or genotyped. S-gene information was available from the three largest PCR-testing laboratories using TaqPath assays, covering 47% of cases identified from community testing during the inclusion period.23UK Health Security AgencyNHS Test and Trace statistics ( England): methodology.https: //www.gov.uk/government/publications/nhs-test-and-trace-statistics-england-methodology/nhs-test-and-trace-statistics-england-methodologyDate: 2022Date accessed: March 9, 2022Google Scholar SARS-CoV-2 vaccinations are recorded in the National Immunisation Management Service.24NHSNational Vaccination Programmes.https: //www.england.nhs.uk/contact-us/privacy-notice/national-flu-vaccination-programme/Date accessed: March 9, 2022Google Scholar Hospital attendance data are recorded in the Emergency Care Data Set25NHS DigitalEmergency care data set ( ECDS).https: //digital.nhs.uk/data-and-information/data-collections-and-data-sets/data-sets/emergency-care-data-set-ecdsDate: Dec 8, 2021Date accessed: March 9, 2022Google Scholar and Secondary Uses Service26NHS DigitalSecondary uses service ( SUS).https: //digital.nhs.uk/services/secondary-uses-service-susDate: Feb 15, 2022Date accessed: March 9, 2022Google Scholar datasets. We linked these datasets by National Health Service ( NHS) number, a unique individual identifier.
In this retrospective cohort study, we included individuals resident in England with laboratory-confirmed SARS-CoV-2 infection with a specimen date in the 6 weeks between Nov 29, 2021, and Jan 9, 2022. Cases were retrospectively followed up until Jan 24, 2022, the date of data extraction. Cases were included ( appendix p 2) if their specimen was whole-genome sequencing-confirmed omicron or delta SARS-CoV-2; genotyping-confirmed omicron or delta SARS-CoV-2; or, if no known sequencing or genotyping-confirmed variant information was available, S-gene negative ( omicron) or S-gene positive ( delta) SARS-CoV-2. S-gene data were only used for test dates up to and including Dec 30, 2021, since increasing incidence of the S-gene positive BA.2 lineage of omicron reduced the positive predictive value of S-gene positivity for delta after that date ( appendix p 4). Reinfections were defined as two positive tests in the same individual taken more than 90 days apart. If there were multiple positive tests within 90 days of each other for the same individual, these were attributed to the same infection episode and the earliest test date in that episode was used.
Cases were excluded if the NHS number recorded was missing or invalid ( since such cases could not be linked to hospitalisation or vaccination records); information was missing for any adjustment variables; there were more than 14 days between the date of the first positive test and the date of the test which led to the variant being identified ( via sequencing, genotyping, or S-gene positivity); or the specimen date was after an individual had died. We also excluded a small number of cases in individuals who had received ( 1) a vaccine other than Oxford–AstraZeneca, Pfizer–BioNTech, or Moderna or more than three doses of vaccine; ( 2) a third dose of vaccine that was not Pfizer or Moderna; or ( 3) a third dose of vaccine less than 80 days after the second dose.
Three hospitalisation outcomes, of differing severity level, were examined: hospital admissions, hospital attendances ( including admissions), and hospital attendances ( including admissions and diagnoses during hospital stay). Specifically, the hospital admissions outcome was defined as hospital admissions occurring 0–14 days after the first positive specimen date of the most recent infection episode, where either length of stay in hospital was 1 or more days; the Emergency Care Data Set discharge field recorded a patient as admitted or transferred; or the patient died in hospital on the same day as hospital attendance. Hospital attendances ( including admissions) was defined as any hospital attendance, including admissions and attendances at accident and emergency departments, 0–14 days after the first specimen date of the most recent infection episode. Hospital attendances ( including admissions and diagnoses during hospital stay) was defined in the same way as hospital attendances ( including admissions), but additionally included cases with a first specimen date occurring during their hospital stay ( hospital-onset cases27Bhattacharya A Collin SM Stimson J et al.Healthcare-associated COVID-19 in England: a national data linkage study.J Infect. 2021; 83: 565-572Google Scholar), to approximately match the definition used in NHS COVID-19 hospitalisation statistics.28NHS EnglandCOVID-19 hospital activity.https: //www.england.nhs.uk/statistics/statistical-work-areas/covid-19-hospital-activity/Date accessed: March 9, 2022Google Scholar The mortality outcome was defined as death occurring 0–28 days after the first positive specimen date of the most recent infection episode, again matching the definition used in routine UK government reporting.
The surveillance activities within which this study was conducted are part of UKHSA's responsibility to monitor COVID-19 during the current pandemic. UKHSA has legal permission, provided by Regulation 3 of The Health Service ( Control of Patient Information) Regulations 2002 to process confidential patient information under Sections 3 ( i) a–c, 3 ( i) d ( i and ii), and 3 ( iii) as part of its outbreak response activities. This study falls within the research activities approved by the UKHSA's Research Ethics and Governance of Public Health Practice Group. Data were shared with the investigators as part of the UK's emergency response to the COVID-19 pandemic, via the scientific pandemic influenza group on modelling ( SPI-M) subcommittee of the UK Scientific Advisory Group for Emergencies. Ethics permission was sought for analyses of these data via Imperial College London's standard ethical review processes and the study was approved by the College's Research Governance and Integrity Team.
Stratified Cox proportional hazards regression was used to estimate hazard ratios ( HRs) for the hospitalisation and mortality outcomes. For the hospitalisation outcomes, cases were followed up from the specimen date until hospitalisation, or censored at the earliest of: death, date of data extraction, and 14 days after their specimen date. For the death outcome, cases were followed up for 28 days. If an outcome occurred on or before the specimen date, the follow-up time was taken to be 0·5 days.
The model used for the primary analysis was stratified by date of specimen, NHS region of residence of the case, 10-year age band, ethnicity group, and vaccination status ( defined as vaccine of the primary series [ Oxford–AstraZeneca vs Pfizer–BioNTech or Moderna ] and the number of doses received); and further included regression adjustments for sex, index of multiple deprivation ( a measure of socioeconomic deprivation for the local area), year of age within each age band, and an interaction term between previous infection status and any history of vaccination ( to allow the effect of previous infection to vary by vaccination status).
The secondary analysis differed from the primary analysis in removing vaccination status from the stratification and instead simultaneously estimating omicron: delta HRs for unvaccinated individuals, variant-specific HRs for different vaccination strata compared with unvaccinated cases, and vaccination status-specific HRs for cases with previous infection compared with those without previous infection.
In sensitivity analyses, we examined the effects of finer age stratification ( appendix p 10); restriction to the subgroup of unvaccinated cases ( appendix p 11); interaction of past infection status with variant ( appendix p 12); alternative variant classifications ( appendix p 13); alternative adjustment or stratification strategies ( or both; appendix pp 14–15); alternative definitions of hospitalisation endpoints ( appendix p 16); epidemic phase bias29Seaman SR Nyberg T Overton CE Pascall D Presanis AM De Angelis D Adjusting for time of infection or positive test when estimating the risk of a post-infection outcome in an epidemic.medRxiv. 2021; ( published online Aug 18.) ( preprint).https: //doi.org/10.1101/2021.08.13.21262014Google Scholar ( appendix p 17); and adjusting for under-ascertainment of past infection status ( appendix pp 18–21).
Data were prepared and statistical analyses were carried out using R ( version 4.1.12; R Foundation for Statistical Computing, Vienna, Austria).
The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.
Between Nov 29, 2021, and Jan 9, 2022, 4 135 347 COVID-19 cases were detected in England, of which 1 516 702 ( 37%) had available variant classification data and met the criteria to be included in the analysis ( figure 1; appendix p 2). These comprised 448 843 delta and 1 067 859 omicron cases ( appendix p 6), with 5983 ( 1·3%) delta cases and 102 957 ( 9·6%) omicron cases ( appendix p 6) being reinfections of people with documented earlier infection 90 or more days before their latest confirmed infection. The appendix ( p 6) shows the distribution of omicron and delta cases by age, sex, ethnicity, residential region, index of multiple deprivation, week of specimen date, vaccination category, and previous infection status. The proportion of cases with omicron increased steadily each week during December, 2021. Individuals with omicron were more likely than delta cases to be from a Black ethnic group, or to live in London or the northwest of England. The patterns of number of cases detected and hospitalisations were similar between the included cases and all cases during the inclusion period ( figure 1, appendix p 4). Compared with cases included in the analysis, cases in individuals who did not fulfil the inclusion criteria had similar characteristics but were slightly more likely to reside in London or the east of England and to be from non-White ethnic groups. As expected, a high proportion of cases were not included after December 30, corresponding to the time when sequencing coverage decreased and S-gene target failure information was not used due to the increase in BA.2 cases ( appendix p 6).Figure 1Cases, hospital admissions, and hospital attendances in those with delta and omicron SARS-CoV-2 variants, between Nov 29, 2021, and Jan 9, 2022Show full captionPlots show number of cases ( A), number of hospital admissions ( B), number of hospital attendances, including admissions ( C), and number of hospital attendances, including admissions and diagnoses during hospital stay ( D), by variant and date of positive test. We included cases whose positive specimen had been classified as delta or omicron based on ( 1) whole-genome sequencing or genotyping or ( 2) for positive tests until Dec 30, 2021, cases whose positive specimen was assessed for S-gene target failure. For illustration purposes, the figure shows the number of cases with S-gene information ( in grey) from Dec 31, 2021, but these cases were not included in the analysis.View Large Image Figure ViewerDownload Hi-res image Download ( PPT)
Plots show number of cases ( A), number of hospital admissions ( B), number of hospital attendances, including admissions ( C), and number of hospital attendances, including admissions and diagnoses during hospital stay ( D), by variant and date of positive test. We included cases whose positive specimen had been classified as delta or omicron based on ( 1) whole-genome sequencing or genotyping or ( 2) for positive tests until Dec 30, 2021, cases whose positive specimen was assessed for S-gene target failure. For illustration purposes, the figure shows the number of cases with S-gene information ( in grey) from Dec 31, 2021, but these cases were not included in the analysis.
Figure 2 presents estimates of the adjusted HRs for hospitalisation and mortality endpoints comparing omicron with delta, across all ages and stratifying by 10-year age group, from both the primary and the secondary analyses ( appendix pp 7–9). Unadjusted HRs ( appendix p 7) give a biased picture of relative severity due to differences in the distribution of omicron and delta cases over time, by age ( even within age bands), by ethnicity, and by residential region. The adjustment for single year of age within age band is particularly important for the youngest band ( < 10 years), where differences in the detailed age distribution of omicron and delta cases ( appendix p 4) can bias estimates otherwise. For the least severe and least COVID-19-specific endpoint examined, hospital attendances ( including admissions and diagnoses during hospital stay), the adjusted HR estimate ( 0·59, 95% CI 0·57–0·61) indicates a lower risk of hospitalisation with omicron versus delta, averaging over all age groups and vaccination strata. The adjusted HR estimate for attendances, including admissions but not diagnoses during hospital stay, is similar: 0·56 ( 0·54–0·58). A greater reduction is estimated for the most severe and specific hospital endpoint, hospital admission up to 14 days after a positive test ( adjusted HR 0·41, 0·39–0·43), with the greatest reduction estimated in the risk of death within 28 days of a positive test ( adjusted HR 0·31, 0·26–0·37).Figure 2Risk of hospitalisation and mortality for COVID-19 cases with omicron compared with delta, overall and by age groupShow full captionPlots show omicron versus delta adjusted HRs for the four endpoints: hospital admission ( A), hospital attendance, including admission ( B), hospital attendance, including admission and diagnosis during hospital stay ( C), and death ( D). Error bars are 95% CIs. HRs of death were not estimated for individuals younger than 30 years due to small numbers. Counts and HR estimates ( unadjusted and adjusted) are given in the appendix ( p 7). HR=hazard ratio. * HRs from the primary analysis, adjusted ( by stratification) for date of specimen, National Health Service region of residence of the case, 10-year age band, ethnicity group, and vaccination status, and adjusted ( by regression) for sex, index of multiple deprivation, year of age within each age band, and an interaction term between previous infection status and any history of vaccination. †HRs from the secondary analysis, for the unvaccinated group only ( intrinsic severity), adjusted for the same confounders, but with vaccination status not used as a stratification variable, but instead used to simultaneously estimate the omicron versus delta HRs for unvaccinated individuals, variant-specific HRs for each vaccination category compared with unvaccinated ( figure 3), and vaccination status-specific HRs for cases with a previous infection compared with those without.View Large Image Figure ViewerDownload Hi-res image Download ( PPT)
Plots show omicron versus delta adjusted HRs for the four endpoints: hospital admission ( A), hospital attendance, including admission ( B), hospital attendance, including admission and diagnosis during hospital stay ( C), and death ( D). Error bars are 95% CIs. HRs of death were not estimated for individuals younger than 30 years due to small numbers. Counts and HR estimates ( unadjusted and adjusted) are given in the appendix ( p 7). HR=hazard ratio. * HRs from the primary analysis, adjusted ( by stratification) for date of specimen, National Health Service region of residence of the case, 10-year age band, ethnicity group, and vaccination status, and adjusted ( by regression) for sex, index of multiple deprivation, year of age within each age band, and an interaction term between previous infection status and any history of vaccination. †HRs from the secondary analysis, for the unvaccinated group only ( intrinsic severity), adjusted for the same confounders, but with vaccination status not used as a stratification variable, but instead used to simultaneously estimate the omicron versus delta HRs for unvaccinated individuals, variant-specific HRs for each vaccination category compared with unvaccinated ( figure 3), and vaccination status-specific HRs for cases with a previous infection compared with those without.
We found considerable variation in the severity of omicron relative to delta cases with age for all endpoints examined ( figure 2). The HRs for hospitalisation did not differ between the two variants in individuals younger than 10 years ( adjusted HR for admission 1·10 [ 95% CI 0·85–1·42 ]); only small ( and sometimes non-significant) reductions in the risk of hospitalisation were seen in 10–19-year-olds, with increasingly large reductions seen with age in 20–69-year-olds ( adjusted HR for admission in 60–69-year-olds 0·25 [ 0·21–0·30 ]). Although HR estimates increased again with age in those aged at least 70 years ( adjusted HR for admission in those aged at least 80 years 0·47 [ 0·40–0·56 ]), they remained substantially below 1. Similar trends were seen for the mortality endpoint in adults over 30 years, but we had insufficient power to examine this endpoint in the younger age groups. In a secondary analysis ( appendix p 10), we disaggregated the younger than 10 years age group into three bands ( < 1 year, 1–4 years, and 5–9 years). The results are suggestive of a higher relative risk in those younger than 1 year than in those aged 1–4 years or 5–9 years, but these differences were not statistically significant.
There was a high level of immunity in the population of England by the time omicron emerged, both from vaccination and previous infection. It is, therefore, informative to disaggregate the HRs for hospitalisation and death into estimates of changes in intrinsic viral severity applying to unvaccinated cases ( figure 2, secondary analysis), and changes in the protection vaccines afford against severe outcomes in breakthrough infections. We estimated a larger reduction ( comparing omicron with delta) in the risk of hospitalisation and death in unvaccinated cases than for all cases ( figure 2, appendix pp 8–9). Figure 3 presents estimates of variant-specific HRs of each hospitalisation endpoint for different vaccination strata compared with unvaccinated cases ( appendix pp 8–9). The relative risk of hospitalisation or death in vaccinated cases compared with unvaccinated cases was lower for delta cases than for omicron cases ( figure 3, appendix pp 8–9). These estimates indicate that the overall observed reductions in hospitalisation and mortality risk understate the intrinsic reduction in the risk of severe infection outcomes associated with the delta to omicron transition, due to those reductions being partially counteracted by reductions in vaccine effectiveness. The largest reductions in vaccine effectiveness against hospitalisation in breakthrough cases were seen for people who had not received a booster dose, particularly for those who had received the Oxford–AstraZeneca vaccine for their primary vaccination series ( figure 3). However, relative protection ( vs unvaccinated) against hospital admission with omicron in breakthrough cases remained above 70% ( HR < 0·3) for all vaccination categories that included a booster dose ( adjusted HR for hospital admission 8–11 weeks post-booster vs unvaccinated 0·22 [ 95% CI 0·20–0·24 ]; appendix pp 8–9). Documented past infection was found to protect unvaccinated cases against hospitalisation ( appendix pp 8–9), with HR estimates of 0·55 ( 95% CI 0·48–0·63) for hospital admission and 0·18 ( 0·06–0·57) for death. These estimates imply a similar level of protection against hospitalisation as that provided by two doses of the Oxford–AstraZeneca vaccine or one dose of the Pfizer or Moderna vaccines ( appendix pp 8–9). In vaccinated cases, past infection did not provide additional protection against hospitalisation ( HR for admission 0·96, 0·88–1·04) beyond that afforded by vaccination, but did provide additional protection against death ( HR 0·47, 0·32–0·68). We found no evidence that the protection against hospitalisation or death afforded by documented past infection differed significantly between omicron and delta cases ( appendix p 12).Figure 3Estimated HRs for vaccination categories, secondary analysisShow full captionVariant-specific HRs of hospital admission ( A), any hospital attendance, including admission ( B), or any hospital attendance, including admission or positive test during hospital stay ( C), by type of vaccine used for doses 1 and 2, number of vaccine doses, and time since last dose, relative to unvaccinated cases. These HRs can be interpreted as 1 – vaccine effectiveness at preventing hospitalisation conditional upon diagnosed infection. Booster doses were Pfizer–BioNTech or Moderna ( not disaggregated). HR=hazard ratio. * Due to small numbers, all cases who had received a single dose of the Oxford–AstraZeneca vaccine were grouped together and not separated by time since vaccine dose.View Large Image Figure ViewerDownload Hi-res image Download ( PPT)
Variant-specific HRs of hospital admission ( A), any hospital attendance, including admission ( B), or any hospital attendance, including admission or positive test during hospital stay ( C), by type of vaccine used for doses 1 and 2, number of vaccine doses, and time since last dose, relative to unvaccinated cases. These HRs can be interpreted as 1 – vaccine effectiveness at preventing hospitalisation conditional upon diagnosed infection. Booster doses were Pfizer–BioNTech or Moderna ( not disaggregated). HR=hazard ratio. * Due to small numbers, all cases who had received a single dose of the Oxford–AstraZeneca vaccine were grouped together and not separated by time since vaccine dose.
Although the HR estimates for unvaccinated cases in figure 2 were derived from a model fitted to all cases, adjusted HR estimates were similar for a model fitted to the subgroup of unvaccinated cases only ( appendix p 11). A sensitivity analysis using imputation to account for under-ascertainment of past infection ( appendix pp 18–21) gave, as expected,8Ferguson N Ghani A Hinsley W Volz E Report 50: hospitalisation risk for omicron cases in England.https: //www.imperial.ac.uk/mrc-global-infectious-disease-analysis/covid-19/report-50-severity-omicron/Date: 2021Date accessed: March 9, 2022Google Scholar slightly higher estimates of omicron: delta HRs than our secondary analysis did ( appendix pp 8–9), but slightly lower estimates of the HRs for vaccinated cases versus unvaccinated for omicron, and lower estimates of the HRs for reinfections versus first infections. Other sensitivity analyses ( appendix p 13) indicated that HR estimates did not vary significantly if only Pillar 2 ( community testing) cases were included in the analysis, but were slightly closer to 1 than in the primary analysis if only sequencing data were used to determine variant status, and slightly further from 1 than the primary analysis if sequencing and genotyping ( but not S-gene target failure data) were used. Estimates were relatively robust to alternative choices of adjustment or stratification ( appendix pp 14–15) and to precise inclusion criteria for hospital endpoints ( appendix p 16). As expected, exploratory analysis of the potential effects of epidemic phase bias29Seaman SR Nyberg T Overton CE Pascall D Presanis AM De Angelis D Adjusting for time of infection or positive test when estimating the risk of a post-infection outcome in an epidemic.medRxiv. 2021; ( published online Aug 18.) ( preprint).https: //doi.org/10.1101/2021.08.13.21262014Google Scholar indicated that the primary analysis might overestimate the omicron versus delta HR if the delay from infection to test is substantially shorter in hospitalised cases than in non-hospitalised cases ( appendix p 17).
Since mid-December, 2021, most new SARS-CoV-2 cases in England have been caused by the omicron variant. Our results suggest that confirmed omicron cases had a 59% lower risk of hospital admission, a 44% lower risk of any hospital attendance, and a 69% lower risk of death than that of confirmed delta cases. We found strong evidence of age-dependence in the magnitude of this risk reduction. In those over 20 years of age, we estimate a significant reduction in the risk of hospitalisation for omicron compared with delta. In cases aged 50 years and above, the estimated reduction in the risk of hospitalisation is 50–75%, depending on the endpoint examined. The magnitude of severity reduction is lower for those older than 80 years, but still over 50% for most endpoints. In individuals aged 0–9 years with a confirmed infection, for whom the risk of disease sufficiently severe to result in death is very low, we estimate that the risk of hospitalisation from omicron infection is not significantly different from that of delta infection. Dividing the 0–9 years age group into three bands ( < 1 year, 1–4 years, and 5–9 years) indicated no significant differences in the omicron: delta HR with age in that age group, although statistical power was more restricted for this finer disaggregation of age. The absence of a difference in the risk of hospitalisation for young children between omicron and delta might be explained by a different clinical presentation of omicron infection in children. Laboratory studies have shown that omicron replicates more in upper airway cells and less in the lungs.30Meng B Abdullahi A Ferreira IA et al.Altered TMPRSS2 usage by SARS-CoV-2 omicron impacts tropism and fusogenicity.Nature. 2022; ( published online Feb 1.) https: //doi.org/10.1038/s41586-022-04474-xGoogle Scholar, 31Hui KP Ho JC Cheung M-c et al.SARS-CoV-2 omicron variant replication in human bronchus and lung ex vivo.Nature. 2022; ( published online Feb 1) https: //doi.org/10.1038/s41586-022-04479-6Google Scholar Children with omicron infection may, therefore, be more likely than those with delta infection to present with fever and upper respiratory symptoms that would trigger clinical pathways for admission, for example to rule out sepsis.32Vihta K-D Pouwels KB Peto TE et al.Omicron-associated changes in SARS-CoV-2 symptoms in the United Kingdom.medRxiv. 2022; ( published online Feb 4.) ( preprint).https: //doi.org/10.1101/2022.01.18.22269082Google Scholar, 33Clark M Walker B Bennett E Herrick A Kenny S Gent N Clinical characteristics of SARS-CoV-2 omicron infection in children under one year.SSRN. 2022; ( published online Jan 14.) ( preprint).https: //dx.doi.org/10.2139/ssrn.4013461Google Scholar Thus, the absence of severity attenuation in children might reflect a lower clinical threshold for hospital admission for young children due to symptoms common to omicron infection, rather than more severe disease.6Wolter N Jassat W Walaza S et al.Early assessment of the clinical severity of the SARS-CoV-2 omicron variant in South Africa: a data linkage study.Lancet. 2022; 399: 437-446Google Scholar, 33Clark M Walker B Bennett E Herrick A Kenny S Gent N Clinical characteristics of SARS-CoV-2 omicron infection in children under one year.SSRN. 2022; ( published online Jan 14.) ( preprint).https: //dx.doi.org/10.2139/ssrn.4013461Google Scholar However, further analyses are required to investigate COVID-19 illness in children and reasons for admission.
We report that pre-existing immunity, both from vaccination and past infection, substantially reduces the risk of hospitalisation. In a secondary analysis, we estimated both variant-specific vaccine effectiveness and age-specific risks of hospitalisation in unvaccinated cases. We estimated lower severity for omicron versus delta compared with the primary analysis, where vaccination status was included in the stratification. This finding is explained by the lower estimates of protection afforded by vaccination against hospitalisation in breakthrough cases for the omicron variant compared with the delta variant. Hence, underlying the observed risks for hospitalisation and death in our primary analysis is a larger reduction in intrinsic severity ( ie, for unvaccinated cases) counterbalanced by a reduction in vaccine effectiveness against omicron compared with delta. However, mRNA booster vaccination was still found to be highly protective against hospitalisation and death in omicron breakthrough cases, in line with studies solely examining vaccine effectiveness.18Andrews N Stowe J Kiresbom F et al.Effectiveness of COVID-19 vaccines against the omicron ( B.1.1.529) variant of concern.NEJM. 2022; ( published online March 2.) https: //dx.doi.org/10.1056/NEJMoa2119451Google Scholar In unvaccinated cases, documented past infection provides moderate protection against hospitalisation and higher protection against death. In vaccinated cases, past infection offered no additional protection against hospitalisation over vaccination alone, but did offer moderate additional protection against death.18Andrews N Stowe J Kiresbom F et al.Effectiveness of COVID-19 vaccines against the omicron ( B.1.1.529) variant of concern.NEJM. 2022; ( published online March 2.) https: //dx.doi.org/10.1056/NEJMoa2119451Google Scholar An imputation-based sensitivity analysis to examine the effect of under-ascertainment of past infections gave slightly higher estimates of the severity of omicron relative to delta, together with estimates indicating a larger protective effect of past infection against all endpoints for unvaccinated individuals, and against hospital admission and death in vaccinated individuals.8Ferguson N Ghani A Hinsley W Volz E Report 50: hospitalisation risk for omicron cases in England.https: //www.imperial.ac.uk/mrc-global-infectious-disease-analysis/covid-19/report-50-severity-omicron/Date: 2021Date accessed: March 9, 2022Google Scholar
To our knowledge, this is the largest study to date to report on the relative hospitalisation and mortality risks for cases with the omicron variant compared with delta. Strengths of the study include the use of a nationwide cohort, covering 37% of all COVID-19 cases in England during the inclusion period. Our results support those of a number of other studies which have reported that omicron has substantially reduced overall severity compared with delta.6Wolter N Jassat W Walaza S et al.Early assessment of the clinical severity of the SARS-CoV-2 omicron variant in South Africa: a data linkage study.Lancet. 2022; 399: 437-446Google Scholar, 7Sheikh A Kerr S Woolhouse M McMenamin J Robertson C Severity of omicron variant of concern and vaccine effectiveness against symptomatic disease: national cohort with nested test negative design study in Scotland. University of Edinburgh, 2021https: //www.research.ed.ac.uk/en/publications/severity-of-omicron-variant-of-concern-and-vaccine-effectiveness-Date accessed: March 9, 2022Google Scholar, 8Ferguson N Ghani A Hinsley W Volz E Report 50: hospitalisation risk for omicron cases in England.https: //www.imperial.ac.uk/mrc-global-infectious-disease-analysis/covid-19/report-50-severity-omicron/Date: 2021Date accessed: March 9, 2022Google Scholar, 9Ulloa AC Buchan SA Daneman N Brown KA Estimates of SARS-CoV-2 omicron variant severity in Ontario, Canada.JAMA. 2022; ( published online Feb 17.) https: //doi.org/10.1101/jama.2022.2274Google Scholar, 10Lewnard JA Hong VX Patel MM Kahn R Lipsitch M Tartof SY Clinical outcomes among patients infected with omicron ( B.1.1.529) SARS-CoV-2 variant in southern California.medRxiv. 2022; ( published online Jan 11.) ( preprint).https: //doi.org/10.1101/2022.01.11.22269045Google Scholar, 11Bager P Wohlfahrt J Bhatt S et al.Reduced risk of hospitalisation associated with infection with SARS-CoV-2 omicron relative to delta: a Danish cohort study.SSRN. 2022; ( published online Jan 14, 2022.) ( preprint).https: //dx.doi.org/10.2139/ssrn.4008930Google Scholar, 12Wang L Berger NA Kaelber DC Davis PB Volkow ND Xu R COVID infection severity in children under 5 years old before and after omicron emergence in the US.medRxiv. 2022; ( published online Jan 13.) ( preprint).https: //doi.org/10.1101/2022.01.12.22269179Google Scholar, 13Veneti L Bøås H Bråthen Kristoffersen A et al.Reduced risk of hospitalisation among reported COVID-19 cases infected with the SARS-CoV-2 omicron BA.1 variant compared with the delta variant, Norway, December 2021 to January 2022.Eurosurveillance. 2022; 272200077Google Scholar, 14Abdullah F Myers J Basu D et al.Decreased severity of disease during the first global omicron variant covid-19 outbreak in a large hospital in Tshwane, South Africa.Int J Infect Dis. 2022; 116: 38-42Google Scholar, 15Peralta-Santos A Rodrigues EF Moreno J et al.Omicron ( BA.1) SARS-CoV-2 variant is associated with reduced risk of hospitalization and length of stay compared with delta ( B.1.617.2).medRxiv. 2022; ( published online Jan 25.) ( preprint).https: //doi.org/10.1101/2022.01.20.22269406Google Scholar, 16Jassat W Abdool Karim SS Mudara C et al.Clinical severity of COVID-19 patients admitted to hospitals in Gauteng, South Africa during the omicron-dominant fourth wave.SSRN. 2021; ( published online Dec 29.) ( preprint).https: //dx.doi.org/10.2139/ssrn.3996320Google Scholar, 17Davies M-A Kassanjee R Rosseau P et al.Outcomes of laboratory-confirmed SARS-CoV-2 infection in the omicron-driven fourth wave compared with previous waves in the Western Cape Province, South Africa.medRxiv. 2022; ( published online Jan 12.) ( preprint).https: //doi.org/10.1101/2022.01.12.22269148Google Scholar However, relatively few studies have examined how the reduction in severity might vary with age. A US study12Wang L Berger NA Kaelber DC Davis PB Volkow ND Xu R COVID infection severity in children under 5 years old before and after omicron emergence in the US.medRxiv. 2022; ( published online Jan 13.) ( preprint).https: //doi.org/10.1101/2022.01.12.22269179Google Scholar compared 3-day follow-up outcomes in individuals younger than 5 years in the previous delta epidemic wave with those in the ongoing omicron epidemic and found a relative risk of emergency department attendance of 0·71 ( 95% CI 0·66–0·75) and a relative risk of admission of 0·33 ( 0·26–0·43). A second study involved a contemporaneous comparison of omicron and delta ( distinguished via S-gene target failure) cases in southern California10Lewnard JA Hong VX Patel MM Kahn R Lipsitch M Tartof SY Clinical outcomes among patients infected with omicron ( B.1.1.529) SARS-CoV-2 variant in southern California.medRxiv. 2022; ( published online Jan 11.) ( preprint).https: //doi.org/10.1101/2022.01.11.22269045Google Scholar and estimated unadjusted odds ratios for hospitalisation in 0–17-year-olds of 0·70 ( 95% CI 0·12–3·97) and 0·94 ( 0·26–3·42) using denominators of only outpatient tests and both inpatient and outpatient tests, respectively. A Danish study11Bager P Wohlfahrt J Bhatt S et al.Reduced risk of hospitalisation associated with infection with SARS-CoV-2 omicron relative to delta: a Danish cohort study.SSRN. 2022; ( published online Jan 14, 2022.) ( preprint).https: //dx.doi.org/10.2139/ssrn.4008930Google Scholar estimated a relative risk of hospitalisation of 1·59 ( 1·09–2·32) in 0–19-year-olds, although this estimate was based on only 31 hospitalisations in that age group. Last, a Norwegian cohort study13Veneti L Bøås H Bråthen Kristoffersen A et al.Reduced risk of hospitalisation among reported COVID-19 cases infected with the SARS-CoV-2 omicron BA.1 variant compared with the delta variant, Norway, December 2021 to January 2022.Eurosurveillance. 2022; 272200077Google Scholar found no significant differences by age in the relative risk of hospitalisation for people younger than 75 years, with a point estimate for individuals younger than 30 years of 0·24 ( 95% CI 0·09–0·60); the study had insufficient power to stratify that age group further.
There are several limitations to our analysis. Stratified analyses have the benefit of controlling for confounding by interactions between variables such as ethnicity, age, and time, but the disadvantage of discarding data from strata where cases from one of the two groups being compared are absent. However, we found estimates showed little sensitivity to the level of stratification used. If rates of progression from infection to symptom onset or test date differ by variant, the HRs presented might be biased. Data on hospital activity, deaths, and vaccination status are subject to reporting delays, and although we mitigated potential biases arising from these delays by using survival analysis stratified by test date, age, and residential region, residual bias might remain. NHS numbers are required to link case data to hospital attendance information and vaccination status; therefore, 89 184 people ( 5·4% of cases) without NHS numbers were excluded from our primary analysis. However, we have no reason to expect a strong association between the absence of NHS number and SARS-CoV-2 variant. During the study period, the omicron variant experienced a rapidly increasing incidence, whereas the delta variant was experiencing a decreasing or less rapidly increasing incidence. These trends could result in epidemic phase bias if infection severity is correlated with time from infection to test.29Seaman SR Nyberg T Overton CE Pascall D Presanis AM De Angelis D Adjusting for time of infection or positive test when estimating the risk of a post-infection outcome in an epidemic.medRxiv. 2021; ( published online Aug 18.) ( preprint).https: //doi.org/10.1101/2021.08.13.21262014Google Scholar Exploratory analysis suggested that such bias would lead to similar or lower HRs between omicron and delta cases compared with those estimated in our primary analysis. It is also unclear whether virologically confirmed cases represent a comparable fraction of underlying infections for the two variants we compared. If the proportion of omicron infections confirmed via PCR testing is lower or higher than for contemporaneous delta infections, our hospitalisation HR estimates will be over-estimates or under-estimates of the true severity of omicron relative to delta. Finally, cases of the BA.2 lineage of omicron were not considered in this analysis, because incidence of that lineage only reached substantial levels after the start of 2022, meaning insufficient data have accumulated to allow reliable severity estimates to be generated.
It is not inevitable that viral evolution leads to lower severity. The risk of hospitalisation appeared to increase when comparing delta with alpha infections21Twohig KA Nyberg T Zaidi A et al.Hospital admission and emergency care attendance risk for SARS-CoV-2 delta ( B.1.617.2) compared with alpha ( B.1·1.7) variants of concern: a cohort study.Lancet Infect Dis. 2021; 22: 35-42Google Scholar, 34Sheikh A McMenamin J Taylor B Robertson C SARS-CoV-2 delta VOC in Scotland: demographics, risk of hospital admission, and vaccine effectiveness.Lancet. 2021; 397: 2461-2462Google Scholar, 35Bager P Wohlfahrt J Rasmussen M Albertsen M Krause TG Hospitalisation associated with SARS-CoV-2 delta variant in Denmark.Lancet Infect Dis. 2021; 211351Google Scholar, 36Fisman DN Tuite AR Evaluation of the relative virulence of novel SARS-CoV-2 variants: a retrospective cohort study in Ontario, Canada.CMAJ. 2021; 193: e1619-e1625Google Scholar and when comparing alpha with previously circulating lineages.36Fisman DN Tuite AR Evaluation of the relative virulence of novel SARS-CoV-2 variants: a retrospective cohort study in Ontario, Canada.CMAJ. 2021; 193: e1619-e1625Google Scholar, 37Nyberg T Twohig KA Harris RJ et al.Risk of hospital admission for patients with SARS-CoV-2 variant B.1.1.7: cohort analysis.BMJ. 2021; 373n1412Google Scholar, 38Bager P Wohlfahrt J Fonager J et al.Risk of hospitalisation associated with infection with SARS-CoV-2 lineage B.1.1.7 in Denmark: an observational cohort study.Lancet Infect Dis. 2021; 21: 1507-1517Google Scholar However, our analysis indicates that omicron is associated with a substantially lower risk of severe outcomes in adults than that of the previously dominant delta variant. Lower severity also needs to be counterbalanced against the ability of a variant to evade pre-existing immunity and thus transmit more readily within highly immune populations. We find evidence of moderate reductions in the protection vaccines provide against hospitalisation in breakthrough omicron cases compared with that of delta, and previous studies indicate substantial reductions in vaccine effectiveness against symptomatic infection.18Andrews N Stowe J Kiresbom F et al.Effectiveness of COVID-19 vaccines against the omicron ( B.1.1.529) variant of concern.NEJM. 2022; ( published online March 2.) https: //dx.doi.org/10.1056/NEJMoa2119451Google Scholar However, we find that receiving an mRNA vaccine booster dose gives over 70% protection against hospitalisation or mortality outcomes in breakthrough omicron cases; absolute vaccine effectiveness will be substantially higher once protection against infection is accounted for.19UK Health Security AgencyCOVID-19 vaccine surveillance report: week 6.https: //assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment data/file/1054071/vaccine-surveillance-report-week-6.pdfDate: 2022Date accessed: March 9, 2022Google Scholar
We were not able to evaluate more detailed measures of relative clinical severity in hospitalised patients ( such as intensive care unit admittance), but our finding that estimated severity reductions comparing omicron with delta are larger for more severe endpoints ( death and hospital admission versus hospital attendance) agrees with observations that the proportion of hospitalised COVID-19 patients requiring intensive care or mechanical ventilation ( or both) has been substantially lower during the omicron wave in England than the preceding delta wave.39UK Health Security AgencyNational influenza and COVID-19 surveillance report: 27 January 2022 ( week 4).https: //www.gov.uk/government/statistics/national-flu-and-covid-19-surveillance-reports-2021-to-2022-seasonDate: 2022Date accessed: March 9, 2022Google Scholar The 80% overall reduction in the intrinsic risk of death that we estimate for omicron infection compared with that of delta will make the goal of living with COVID-19 in the absence of socially and economically disruptive public health interventions substantially easier to achieve at the current time. However, it is not guaranteed that future variants will have a similarly reduced severity. It is, therefore, crucial that sufficiently detailed and systematic surveillance is maintained to allow timely detection and characterisation of new viral lineages.
TN, NMF, SFlax, MC, DDA, AMP, and ST conceptualised the work. SGN, HHW, NA, WH, MK, PB, AZ, JLB, MC, NAA, KH, RH, AC, GD, and ST curated the data. TN, NMF, SFlax, SFunk, SA, SB, and ST did the formal analysis. NMF, SB, SFunk, ACG, DDA, and AMP acquired funding. TN, NMF, SB, EV, SRS, DDA, and AMP developed the methodology. NMF, MC, GD, DDA, AMP, and ST handled project administration. TN, NMF, WH, and SA wrote the software. NMF, MC, GD, DDA, AMP, and ST supervised the work. TN and NMF validated the data. TN and NMF were responsible for visualisation. TN, NMF, SGN, DDA, AMP, and ST wrote the original draft of the manuscript. All authors reviewed the manuscript.
Although all data used in this analysis were anonymised, the individual-level nature of the data used risks individuals being identified, or being able to self-identify, if the data are released publicly. Requests for access to the underlying source data should be directed to UKHSA. The code used to analyse the data is available on GitHub.
GD declares that his employer UK Health Security Agency ( previously operating as Public Health England) received funding from GlaxoSmithKline for a research project related to influenza antiviral treatment. This preceded and had no relation to COVID-19, and GD had no role in and received no funding from the project. All other authors declare no competing interests.
We thank staff at UKHSA and members of the UK Government SPI-M committee and the UKHSA Variant Technical Group for valuable discussions. This work was supported by grants from the UK Research and Innovation ( UKRI) Medical Research Council ( NMF, WH, SB, EV, ACG [ Centre for Global Infectious Disease Analysis; MR/R015600/1 ], DDA, AMP [ MC/UU/00002/11 ], and SRS [ MC/UU/00002/10 ]); Medical Research Council UKRI–Department of Health and Social Care National Institute for Health Research ( NIHR) COVID-19 rapid response call ( NMF, SB [ MR/V038109/1 ], TN, AC, DDA, and AMP [ MC/PC/19074 ]); the NIHR Health Protection Units in: Modelling and Health Economics ( NMF, WH, SB, EV, AC, and ACG [ NIHR200908 ]), Behavioural Science and Evaluation ( AC and DDA), and Respiratory Infections ( JLB); Wellcome Trust ( SFunk and SA [ 210758/Z/18/Z ]); philanthropic funding from Community Jameel ( NMF, WH, SB, and EV); and the UKRI Engineering and Physical Sciences Research Council ( SFlax [ EP/V002910/2 ]). The funders played no direct role in the study. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.
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Omicron: fewer adverse outcomes come with new dangersWith wave after wave of SARS-CoV-2 variants, COVID-19 patients filled the worlds ' hospitals and morgues because not everybody had access to vaccines or were willing to be vaccinated.1,2 Omicron ( B.1.1.529) is no different. Although most scientists were expecting an increase in cases during late 2021, it was surprising that vaccinated and previously infected people were contracting the novel omicron variant so easily and how fast it was transmitting,3 which raised several questions. Would existing vaccines still prevent SARS-CoV-2 infection? 4 Was omicron more transmissible than previous variants? 5 What were the consequences of omicron's wide and rapid spread infecting millions of people, including a high number of breakthrough cases? Would it have worse or better outcomes than the worst SARS-CoV-2 variant on record, the delta variant ( B.1.617.2)? In The Lancet, Tommy Nyberg and colleagues report their findings about omicron for individuals who are vaccinated, previously infected, or unvaccinated. Full-Text PDF | tech |
Atlanta spa shootings: Tragedy brought national attention to violence against Asian Americans |
Robert Peterson struggled for months to stop thinking about the day his mother and seven other people, mostly Asian women, were shot and killed last year at Atlanta-area spas.
He's found some comfort living at the Norcross, Georgia, home his mother Yong Ae Yue worked hard to own and in the memories of the many nights they played poker together, but Peterson says he can't let others forget that his family and the Asian American community see the March 16, 2021 killings as hate crimes.
The
gunman
may have not said any racial slurs out loud during the shooting spree, but his actions `` are the proxy of his misogyny, of his racism, '' Peterson, 39, said.
Since the mass shooting, the gunman has pleaded guilty to four of the killings in Cherokee County and was sentenced to life in prison. But he still faces an additional 19 charges in nearby Fulton County, where prosecutors have said they will be pursuing the death penalty for hate crimes targeting the sex and race of the victims.
Ignoring this racial aspect and the longstanding objectification of Asian women has only intensified the trauma of losing his mother and fuels his fight for justice, Peterson told CNN.
Read More
Asian Americans are feeling on edge. How you can get help or help those in need
The spa killings forced a debate about racism toward the Asian community in the United States, but reports of Asian people being assaulted and harassed had already been increasing since the start of the Covid-19 pandemic.
A year later, not much has changed in America, according to advocates, survivors of the violence and their family members. The alleged gunman in the Atlanta attacks has not been tried in a state or federal court for a hate crime, anti-Asian racism is still continuously being reported, and challenges of proving bias against the Asian American community persist.
`` We see swastikas or Nazi symbols and salutes. In the Asian American community there's not something that unifying that everybody understands as something that's geared towards, intimidating or trying to hurt the AAPI community, '' said Byung `` BJay '' Pak, a former US attorney in Atlanta who represents Peterson.
First test of the hate crimes law in Georgia
Yue, 63, and the other seven victims, Daoyou Feng, 44; Paul Michels, 54; Xiaojie `` Emily '' Tan, 49; Delaina Yaun, 33; Suncha Kim, 69; Soon Chung Park, 74; and Hyun Jung Grant, 51, were killed at three spas across the Atlanta area.
Yong Ae Yue, center, was one of the eight people killed in the Atlanta spa shootings and is remembered by her sons Elliott Peterson, left, and Robert Peterson, right.
Robert Aaron Long, the then-21-year-old suspect in the shootings, told authorities he was distraught due to what he described as an addiction to sex. His claim sparked a debate over the motive behind the attack as well as numerous calls in support of a hate crime designation — a trend that continues today.
`` We have to tell and reckon with the whole truth of why they're not here with us today: systemic racism, White supremacy, gender-based violence, the enduring impact of war, both here and in Asia, '' Phi Nguyen, the executive director of
Asian Americans Advancing Justice - Atlanta
, said about the victims during a Saturday memorial event in Brookhaven, an Atlanta suburb.
Yong Ae Yue had been working for a few months at Aromatherapy Spa in Atlanta when she was shot and killed there on March 16, 2021.
The Fulton County District Attorney's Office did not respond to multiple requests for comment but a pretrial hearing is set for April 19 in Long's case.
The case is expected to be the first test of the hate crimes law passed by the Georgia Legislature after the deadly shooting of 25-year-old Ahmaud Arbery. The law allows prosecutors to classify existing charges as a hate crime before trial. A jury would first have to determine guilt, and then consider whether it's a hate crime.
Pak, who also represents the family of Suncha Kim, said Long's case won't change Long's potential life in prison or death penalty sentence but it would be symbolically important.
`` My wish for our clients is that they have their day in court and they get an answer for a situation that's just incomprehensible to try to bring some logic to it and to see justice done, '' Pak said.
So far, federal authorities have not filed hate crimes against Long. A Justice Department spokesperson told CNN the federal investigation of the Atlanta spa shootings remains open as officials continue monitoring the state cases.
Rep. Judy Chu, a California Democrat and chair of the Congressional Asian Pacific American Caucus who previously was concerned that Long would not be charged with a hate crime, told CNN she was encouraged by the response of state and federal officials. Fulton County prosecutors are treating the case as a hate crime and the Justice Department `` committed to examining the evidence to see if it meets the criteria for a federal hate crime, '' Chu said.
`` There is no question to me that these murders were deliberate acts of hate, '' Chu said in a statement.
Robert Peterson moved to his mother's home in Norcross, Georgia, where they spent many night playing poker.
' I miss the small things '
As Peterson and his family await a trial, he tries not to feel the loss of his mother at every corner of their home, especially in the kitchen, where he proudly keeps the ceramic bowls and pots that his mother used to teach him how to cook his favorite dish, Kimchi-jigae, a type of traditional stew.
Attacks on Asian American women are igniting a conversation about public safety
`` I miss the small things. I miss her needing me to change the light bulb, update her computer, go to the store to pick up cat litter, or carry a 24-case of water, '' Peterson said. `` You know, those are the things that I wish she could ask me today. ''
Yue was a traditional Korean woman, a mother who taught her biracial sons to fully embrace their Asian heritage and do good work, he says. She understood the outrage and pain after the killings of Black men and women by police, Peterson says, just as she was frightened by the rise in anti-Asian attacks at the beginning of the pandemic.
`` She loved America, she loves Georgia but it was not lost on her, as most ( Asian) women in America feel today, the threat of violence. It's a constant thing that is a hovering over their lives in their daily activities, '' he said.
If he could talk to her today, Peterson said his mother would be proud that he's willing to speak up for her and the other victims.
More Asian Americans are under attack
In the year since the Atlanta spa shootings, violent assaults and harassment have left Asian Americans across the country afraid and physically hurt.
One of them is Hoa Nguyen, a 68-year-old grandmother in Brooklyn who was punched in the face by a stranger on January 19 while she was on her way to the market.
`` I turned my head to the right and he punched me two more time behind my ear on the left side. Then he went back to walk the way he had come, '' Nguyen said.
While Nguyen, who is Vietnamese, did not suffer major injuries, she no longer feels safe walking on the streets as much as she did before, or even taking the bus or the train to visit her daughter in Brooklyn's Dumbo neighborhood.
`` We 've never had to look over my shoulders walking around the city and now, every time I walk outside, I 'm looking over my shoulder, '' said Nguyen's son, 42-year-old Khanh Nguyen.
Hoa Nguyen, right, was punched in the face on January 19, 2022 in Brooklyn, New York, police says. Her son, left, Khanh Nguyen, says the family has been harassed online since the attack.
The suspect, Mercel Jackson, 51, was arrested and has been charged with assault, harassment and hate crime charges, according to the Brooklyn District Attorney's Office. He told police he `` doesn't like how Chinese people look, '' he thinks `` Chinese people look like measles, '' and `` doesn't like Chinese people looking at him, '' according to court documents.
The attack led neighbors and several nonprofit organizations around New York to offer the Nguyen family their emotional and legal support, Khanh Nguyen said. Unfortunately, it sparked another type of anti-Asian hate toward the family.
`` No one goes up to the streets and yells things at us but despite the sadness of these stories, you still have people going online and spewing hate towards us, '' he said.
Just in New York, there were 131 incidents confirmed to have an anti-Asian bias motivation last year, according to data from the NYPD. That's a significant increase from 27 incidents reported in 2020 and one in 2019.
The full scope of the violence across the nation is unclear. Statistics from advocacy group Stop AAPI Hate collected after the start of the Covid-19 pandemic suggest there have been more than 10,000 anti-Asian hate incidents in the US but the organization's data is crowdsourced, self-reported and not independently verified.
But even when those incidents are reported, reaching a hate crime conviction is challenging, said Jennifer Wu, an attorney representing the Nguyens and the family of
GuiYing Ma
, a 61-year-old woman who was attacked in Queens by a man with a rock and who died last month.
In New York, which has a hate crime penalty-enhancement law like in Georgia, the statute requires the bias to be the `` whole or substantial factor '' motivating an attack.
That's a high standard, Wu says, because it `` requires you to get into the mind of the perpetrator '' and there could be more than one contributing factor, Wu says.
`` The way the law has treated hate crimes is to force people to choose one reason why the hate crime is committed, '' Wu said. The law is not structured in a way that acknowledges the reality that the reason we love and hate people is for a multitude of reasons and not a single exclusive reason. ''
For Peterson, who lost his mother in the Atlanta spa shootings, there was not just one reason why the victims were targeted. His mother was not just at the wrong place, at the wrong time, he said. Peterson believes the suspect had in mind their racial identity, their gender, their workplace, and what that represented to him.
`` She wasn't just Asian, and she wasn't just a woman. These two are inextricably linked. She is both of these things simultaneously, and you can't separate one from the other, '' Peterson said. | general |
Xi Jinping: Russia's war and surging Covid in China are disrupting the Chinese leader's big year |
In a year when all Xi Jinping craved was for things to be stable, 2022 is shaping up to be anything but.
After years of careful preparation, the Chinese leader is expected to step into an almost unprecedented third term at the helm of the country and its Communist Party this fall.
But instead of a smooth ride, dual crises are threatening to upend the status-quo, with China's
largest outbreak of Covid-19
in two years emerging at home while overseas, Russia embarks on a brutal,
widely denounced
invasion of Ukraine.
The war comes just weeks after Beijing declared
a limitless partnership
with Moscow, putting China's diplomats on the back foot and pushing China to make an existential choice about its future international role.
While Xi's path to a third term may not be imperiled by these twin crises, both will need to be navigated carefully as the 68-year-old leader steers the country toward its twice-a-decade leadership reshuffle at the 20th Party Congress this fall.
Chinese President Xi Jinping, center, and other officials sing the Chinese national anthem during a ceremony to mark Martyr's Day at Tiananmen Square in Beijing, in September 2019.
Read More
`` From Beijing's perspective there is no higher priority than stability ahead of the Party Congress -- as we all know it's by no means an election, but this is the closest you might come to seeing a 'campaign season ' in China, '' said Natasha Kassam, director of the Public Opinion and Foreign Policy Program at the Australia-based think tank the Lowy Institute.
`` We know that most opposition to Xi has been eliminated... but there is still the expectation of delivering on particular needs for the majority of people, '' she said.
That may be especially true for a leader who has spent years
consolidating power
and oversaw the
removal of constitutional term limits
on the presidency -- paving the way for him to stay on top in the closed-door, elite political process that decides who will lead China for the next five-year term.
In doing so, Xi has placed himself at the center of the party and state in a way not seen since Communist China's founding father
Mao Zedong
decades ago -- a position from which the country's successes can rest on his shoulders, but so too can its failures.
Complicated friendship
As Russian tanks, soldiers and fighter planes advanced into Ukraine from multiple sides last month, China appeared to some observers to have either been playing along -- or played.
Days before the invasion, Beijing continued to
publicly dismiss US intelligence
that a Russian assault of its neighbor was imminent, despite Xi and Russian President Vladimir Putin earlier that month signing a 5,000-word joint joint statement that included an expression of their shared disapproval of NATO expansion -- an issue that's been key to Putin's rationale for his assault on Ukraine.
The importance of that meeting -- the 38th between the two leaders since 2013 -- was only underscored by the fact it was
Xi's first in-person
summit with another head of state in nearly two years, as China has maintained stringent control over its border during the Covid-19 pandemic.
While views diverge on how much Xi may have known about Putin's true plans, as Russia's unprovoked invasion wears on, China's position of both saying it respects international norms, while not condemning Russia, is growing increasingly untenable.
China's amateur investors are betting big time on a boost to Russian trade
`` Now this ( situation) is impossible for China -- China will either have to be in support of global institutions or it will be against them. That's it, '' said Victor Shih, a professor at University of California San Diego's School of Global Policy and Strategy. `` ( For China, it's turned) into a diplomatic and potentially economic headache. ''
That risk for China, and by extension Xi, is two-fold: on the one hand, if it violates a raft of
stringent sanctions
imposed by the West in order to lend support to Russia, Chinese enterprises involved could be hit by secondary sanctions -- potentially signing their economic death on the global market.
But more pressing is the risk Beijing's stance could sink relations between China and its major trading partners in the West. Even before Russia's invasion of Ukraine, these ties were seeing significant strain. Washington and Beijing have been at loggerheads for several years over issues like trade, Taiwan, and China's human rights record, and there were signs Europe was moving in a similar direction.
Last year, a
highly anticipated investment deal
between the European Union and Beijing stalled as tensions flared over China's alleged human rights abuses against Muslim minority groups in its western region of Xinijang.
And when it comes to Ukraine, pressure is already very much on China to choose a side, with US officials saying this week that
Moscow has asked Beijing for military aid
-- a claim both China and Russia deny.
US State Department spokesperson Ned Price said Monday the United States is `` watching very closely the extent to which the ( People's Republic of China) provides any form of support, whether that's material support, whether that's economic support, whether that's financial support to Russia. ''
China has expressed some openness to providing military and financial aid to Russia, US cable suggests
On Tuesday, Qin Gang, China's ambassador to the US, pushed back on `` assertions that China knew about, acquiesced to or tacitly supported this war '' in an op-ed in the Washington Post, saying instead `` had China known about the imminent crisis, we would have tried our best to prevent it '' and that Beijing was committed to working for peace.
All this may be making some people in Xi's China uncomfortable.
`` There are certainly differences of opinion ( among) Communist Party members and the business community, who are concerned with China being tied to a pariah state and concerned about falling foul of very dramatic sanctions, '' Kassam said.
`` China's trade relationship with the world's democracies is many magnitudes larger than it is with Russia, '' she said. Trade between the European Union and China topped $ 800 billion last year and US-China trade was over $ 750 billion, according to China's
official data
, while its trade with Russia was just under $ 150 billion.
An example of these differing opinions was on show in a
commentary
published last week by Shanghai-based scholar Hu Wei, vice-chairman of the Public Policy Research Center of the Counselor's Office of the State Council, who warned China's path of not condemning Putin could lead to isolation.
Russian President Vladimir Putin ( C) reviews a military honour guard with Chinese leader Xi Jinping ( L) in Beijing on June 8, 2018.
`` If China does not take proactive measures to respond, it will encounter further containment from the US and the West, '' Hu wrote in a piece published in Chinese and an English translation in the US-China Perception Monitor, a publication of the US-based nonprofit The Carter Center --
which said
the Monitor's website was blocked in China not long after the piece was published.
`` China should avoid playing both sides in the same boat, give up being neutral, and choose the mainstream position in the world, '' Hu said.
But while such concerns may be bubbling under the surface, experts remain skeptical they represent a strong or even dominant view in the Communist Party, given Xi's own personal embrace of Putin in recent years.
And to move away from Putin would be to risk questioning Xi. `` In the short term, ( Beijing) can not change its 'no limits ' partnership with Russia because it will imply that Xi was wrong to get China into the difficult position in the first place, '' said Yun Sun, director of the China Program at the Washington-based Stimson Center think tank.
`` Xi is aiming for the third term, and this would be a main stain on his record. ''
Covid crisis
But looming concerns about whether China's economy could be impacted by global turmoil sparked by Russia's war, or any penalties from a further break with Western partners, are coupled with another challenge to stability -- both economic and political -- on China's home front.
There, new Covid-19 cases have been reported in the thousands for several days in the largest outbreak in roughly two years. It's a sharp jolt for a country that has assiduously maintained a `` zero-Covid '' posture at great cost -- shutting its borders to most foreigners since March 2020, rolling out a complex digital tracking system for each individual, and enacting mass testing and snap lockdowns even when a handful of cases were found.
China's leaders have freely equated that policy, and its relative success at controlling Covid-19, to what they claim is the superiority of the Chinese system over that of Western democracies, where the virus spread rampantly. Such rhetoric has not only played out on Chinese state media -- where the horrors of Covid-19 overseas are voraciously covered -- it's also been part of Xi's own case to the world about why China is an exemplary global leader and force for good.
For more than a year, analysts have suggested China would not relax its stringent zero-Covid policy, even as the rest of the world opens up, until after 2022's Party Congress was over and Xi cemented his third term -- as a widespread outbreak would challenge that carefully cultivated image.
Residents in China's port city of Shenzhen queue up for Covid-19 tests on March 13, 2022.
`` The last thing that the Chinese leaders want is to have a nationwide, major Covid-19 outbreak that overwhelms the hospitals... and could contribute to social and political instability, '' said Yanzhong Huang, a senior fellow for global health at the Council on Foreign Relations.
`` A government failure to effectively respond to such a crisis could translate into a legitimacy crisis ( ahead of the Party Congress), '' he said.
But now that risk is playing out in real time as authorities around the country race to lock down cities and stamp out cases -- with no guarantee these measures will be effective against the newer and highly infectious Omicron variant.
As of Tuesday, five Chinese cities with more than 37 million residents were under various forms of lockdown, and concerns have been growing over the economic fallout from China's stringent control measures.
In China, 37 million people are in Covid lockdown. Here's what we know
At least one major company, Apple supplier Foxconn, suspended operations in Shenzhen, before moving into a `` closed loop '' system where employees who live on campus can work, as the tech hub went under a soft lockdown after recording 66 Covid-19 cases on Saturday.
A research note from analysts at financial services group Nomura on Friday said the costs of China's zero-Covid strategy `` will rise significantly as its benefits decline, '' making it `` much harder for Beijing to achieve its `` around 5.5% '' GDP growth target for 2022 '' -- a figure that was already the
country's lowest official growth target
in three decades.
But China's leaders, and Xi, may be worrying about more than the macro-economic outlook ahead of the Party Congress, according to Lowy Institute's Kassam. If sustained, widespread lockdowns could strike at the welfare and livelihoods of the more economically vulnerable in the country -- groups whose economic security has been part of
Xi's well publicized
signature focus through his first two terms as President.
That could see the government more willing to roll out tools to prop up the economy this year than in the past if Covid-19 is not brought under control swiftly, Kassam said.
`` Because this one will impact 'everyman ' first... and if we come back to this idea that we are in 'campaign season ' -- so to speak -- that becomes really important. ''
While headwinds from these events may have an impact on `` everyman, '' in China there is one man who is carefully surveying the landscape and pulling the strings.
As these dual crises evolve during a highly sensitive year, experts will be watching closely to see to what extent Xi moves to recalibrate China's positions both overseas and at home to ensure there are no threats posed to his historic transition into a third term.
Because, as China's latest government work report -- often seen as the Chinese equivalent of the State of the Union address in the US -- repeatedly made clear: Xi Jinping is the `` core '' of the Communist Party leadership. And it is of the highest priority to `` maintain overall social stability to welcome the victory of the 20th Party Congress. '' | general |
Wall Street eyes Fed interest rate hike |
The Federal Reserve will likely
hike interest rates
on Wednesday, marking the end of the ultra-low rate environment the pandemic ushered in two years ago.
The market expects a quarter-percentage point to be added to the benchmark rate, lifting it above zero. It would be the first rate hike since late 2018.
The Fed hopes that higher rates will curb demand and help bring
America's soaring inflation
back to a more palatable level and towards the central bank's long-term goal of 2%.
But it's coming at a tricky time.
Even though the US economy has been on a strong recovery path from the pandemic recession, higher energy prices as a result of Russia's war in Ukraine are a
new dark cloud on the horizon
.
Read More
Hiking rates while ensuring the economy continues to expand is the latest challenge for Fed officials who have spent the past two years navigating coronavirus shutdowns and the worst labor market shock in history.
Federal Reserve Chairman Jerome Powell has warned that the war could stoke inflation and cause households to cut back on spending. But he has also indicated that the conflict has not changed the central bank's thinking on interest rates.
`` To ensure that the economy continues to expand and avoid recession, I do think that it's important to normalize interest rates, '' Moody's Analytics chief economist Mark Zandi told the House Financial Services Committee
last week.
`` The key thing for lower- and middle-income households is to avoid recession, '' Zandi said.
That is easier said than done.
Goldman Sachs
(
GS
)
economists said last week that the chance of a recession in the United States over the next year has risen
as high as 35%.
The investment bank sees little to no growth during the first three months of 2022.
Lower-income households already struggling with high prices would be hit hard by a downturn.
The pandemic inflation trend began with products and services that were linked to high demand and supply chain disruption, such as cars. But higher prices soon spread throughout the economy. In the year ended in February, US consumer prices rose 7.9% without seasonal adjustments, the Bureau of Labor Statistics reported last week. It was the biggest increase since January 1982.
With
prices for food
and gas rising swiftly, the Fed finds itself with no choice but to act. | general |
Motorcyle-mad Indonesia Revs Up For First GP In 25 Years | Indonesia hosts its first motorcycle grand prix in 25 years on Sunday, confident that concerns surrounding the new track will be forgotten once racing begins in front of a sell-out crowd.
The archipelago nation of 270 million people is motorbike mad -- many get around on two wheels -- and there is a palpable sense of excitement at the prospect of world-class racing returning.
Even President Joko Widodo is a fan and tried out the Mandalika International Street Circuit when he officially opened it in November, having a go on a custom-made green Kawasaki bike.
Sunday's race is the second stop on the 2022 MotoGP calendar after the opening race in Qatar two weeks ago, won by Enea Bastianini of Italy.
The new 4.3-kilometre ( 2.7-mile) circuit hugs white-sanded coastline on the island of Lombok, which wants to rival its better-known neighbour, Bali, as a tropical holiday destination. The track complex is part of those ambitions.
There is great anticipation, but also angst and anger -- the circuit is part of a mega-tourism infrastructure project denounced by the United Nations over the eviction of families. Some refused to leave and were still encamped at the track in November.
When the track hosted a World Superbike race that same month there were concerns about the track surface.
Riders during MotoGP testing in February made similar complaints, saying the track was dirty and breaking up dangerously, with debris and stones flying into them like bullets.
Turn one was of particular concern. World champion Fabio Quartararo reportedly called it `` a total disaster ''.
Organisers dismissed those fears as teething problems, carried out urgent resurfacing in places and are confident the track is now in tip-top condition.
`` The condition that must be improved was the peeling asphalt, which created no grip for the racers, '' Cahyadi Wanda, vice-president of the Mandalika Grand Prix Association, told AFP.
`` This work was completed on March 9. All of that work was 100 percent complete. ''
Wikanto Arungbudoyo, a MotoGP fanatic, is keeping his fingers crossed.
`` I am eager to know what the riders say about the resurfaced track. Will we get positive feedback from them or maybe, God forbid, the problem gets worse?
`` Indonesia is very much capable of holding a grand prix here, '' he added.
The country hosted motorcycle grand prix in 1996 and 1997 near the capital Jakarta, but its ambitions of becoming a mainstay of the sport were torpedoed by the Asian financial crisis.
For all the track's breathtaking scenery and the excitement, there are other controversies.
Several villages were relocated -- voluntarily or by force -- to make way for the circuit's construction.
When AFP visited in November about 40 families, along with their cattle and dogs, were still holding out in the centre of the circuit despite alleged intimidation to cede their land.
Environmentalists also question the wisdom of hosting large-scale events on an island under threat from natural disasters.
Lombok is still struggling to rebuild following an earthquake in 2018 which killed more than 500 people and caused extensive damage.
Authorities hope the circuit complex will create thousands of jobs and attract up to two million foreign visitors a year, as Indonesia attempts to reinvigorate its crucial tourism industry which has suffered badly in the coronavirus pandemic.
Covid restrictions mean there will not be many international visitors this time and tickets are too expensive for local people.
But underlining the excitement, all 63,000 tickets for Sunday's race day have sold out and those who can not afford a ticket will watch from a nearby hill.
Yurson Hadi, head of Lombok's tourism agency, said that many hotels -- among them five-star ones -- were also all booked up.
`` Hopefully this event will be a good start for tourism recovery in Lombok and also Indonesia, '' he said. | business |
When Will the Chip Shortage End? U.S., EU Spend Billions in Race to Beat China | Magdeburg in former East Germany is famous for its towering gothic cathedral, and not a lot else. It’ s now about to play a key role in U.S. and European efforts to tilt the global balance of power.
Intel Corp. unveiled plans on March 15 to build a giant, 17 billion-euro ( $ 18.7 billion) factory making cutting-edge semiconductors in the city, adding to new plants in Arizona and Ohio the company announced over the past six months.
They are part of Chief Executive Officer Pat Gelsinger’ s plan to wrest control of production from Asia and tackle the global shortage of chips exacerbated during the COVID-19 pandemic and exposed again following Russia’ s invasion of Ukraine. “ The situation reinforces why we’ re doing this project, and the need for globally resilient and balanced supply chain, ” Gelsinger said after revealing the Magdeburg site.
His ambition is one that the U.S. and European Union are promising to back with a combined $ 100 billion in a subsidy race to reduce reliance on imports just as China plans to turn itself into a chip powerhouse. Behind closed doors, though, some people in the industry are getting increasingly concerned that the push to make the West more competitive might backfire.
Their worry is not only that the money will be too little, too late, but the political strings attached to the aid may complicate global supply chains further. Different parts of the planet will compete to secure supplies while championing domestic plants that can’ t yet fill the void.
The dearth of semiconductors has brought some car manufacturing to a halt and delayed shipments of game consoles and smartphones, waking Washington and Brussels up to the fact that their continents are dependent on a handful of regions for the key parts. The most notable is Taiwan, a geopolitical hotspot because of historically tense relations with China and one whose vulnerability is under more scrutiny since Russia’ s invasion of its smaller neighbor.
Yet, however dysfunctional it may look at the moment, the supply chain is global and fully integrated. Unpicking it could carry greater risks, said Rudi De Winter, CEO of German chip maker X-Fab Silicon Foundries.
The semiconductor industry “ is a very global business, and it has done well being a global business, ” he said. “ This whole trend of trying to make things sovereign in every region and having its own supply chain is rather driven by politics and not by the semiconductor industry. ”
Russia, which has been sanctioned by the U.S. and Europe, now is a clear example of how semiconductors have become increasingly important political tools. The items were some of the first goods that Washington and Brussels targeted to cut Russia off from the global economy, and they’ ve continually threatened more action. Manufacturing of cars in Russia, for example, has already been hit.
On the flip side, Russia and Ukraine export palladium and neon used to make semiconductors, though chipmakers have downplayed the potential impact.
U.S. Secretary of Commerce Gina Raimondo said in an interview on March 9 that if Chinese companies defy U.S. restrictions against exporting to Russia, Washington could shut down companies by cutting them off from the American equipment and software they need.
Semiconductors and other high-tech are becoming “ weaponized ” with the current trade wars and supply chain issues, said Rafael Laguna de la Vera, CEO of SPRIN-D, Germany’ s federal agency for disruptive innovation. “ This is why regions need to invest into high tech to get resilient, ” he said.
The U.S. and Europe want to claw back their share of the chip market after collapses in recent decades. The U.S. accounted for nearly 40% of the world’ s silicon wafer production in the 1990s, while the EU accounted for more than 20%, according to figures cited by Washington and Brussels. The U.S. is now below 15% and the EU has about 10%.
In an effort to shift production away from Asia, President Joe Biden plans to put $ 52 billion into domestic semiconductor research, development and production as part of its broad China competition bill, though it is still awaiting approval. The EU’ s 27 member states, meanwhile, are only just scrutinizing the European Commission’ s recent proposal worth $ 48 billion to build up the bloc’ s chip capacity.
China has already been spending what could amount to $ 150 billion by 2030 to jumpstart production. The country is still far behind, especially when it comes to advanced chip making, but it’ s catching up quickly.
“ We’ re laser-focused on revitalizing America’ s semiconductor industry, ” Raimondo said at Intel’ s new site in Ohio in January. “ Semiconductors are the essential building blocks of our modern economy. ”
Some members of Congress, though, want to see the taxpayer funds attached to guardrails that prevent companies from using the money to invest in China while Intel at one point lobbied against the taxpayer funds going to firms headquartered abroad.
In the past, things were simple for chip producers, said Kurt Sievers, CEO of Dutch chipmaker NXP Semiconductors NV. Companies “ could just choose production locations and R & D locations wherever you wanted, ” he said. “ But I think we just have to stay realistic: Maybe these times are over. Now we are dealing with the world as it is going to evolve. ”
Intel CEO Gelsinger is a major force behind government investment in new plants. Despite the naysayers, he believes public funding could help Intel lower the cost of trying to catch up on cutting-edge chips after falling behind Taiwan Semiconductor Manufacturing Co., known as TSMC, and South Korea’ s Samsung Electronics Co. It would also make the U.S. and Europe more self-reliant.
“ Let’ s not waste this crisis, ” Gelsinger told Bloomberg earlier this year. “ It’ s good economics, but it’ s also national security. ” Intel’ s new plant in Magdeburg, which will start production in 2027, is part of an 80 billion-euro package of investment in Europe by the Californian company.
Whether the numbers stack up remains to be seen. The U.S. and Europe have some serious catching up to do, said SPRIN-D’ s de la Vera. Japan, for example, is also promising state aid to boost production. New facilities include a $ 7 billion factory planned by TSMC in conjunction with Sony Group Corp. and Denso Corp.
South Korea also wants to become the world’ s biggest chip producer, with companies and the government pouring a total $ 450 billion into the industry by 2030.
Achieving economies of scale that can compete with Taiwan’ s business model is also going to be tough if each region is racing to build its own capacity. TSMC accounts for more than 50% of the global foundry market, or the business of purely making chips for other companies. Its customers include Apple Inc., which relies on Taiwanese chips for iPhones.
Indeed, the reliance on TSMC is the core concern: an invasion of the island by China would leave the world’ s most advanced chips in the hands of Beijing. U.S. academic Jared McKinney recently suggested in a U.S. Army journal that Taiwan should protect itself by threatening to destroy chipmaking facilities so that Beijing would see its tech industry “ immobilized ” should it invade. He called it a “ broken nest ” strategy.
TSMC will have a new U.S. location operating in Arizona in two years and is now mulling a potential plant in Germany after European carmakers repeatedly expressed concerns about the impact from the chip shortage. But Taiwanese industry insiders remain skeptical of plans to relocate production back to the West.
“ It’ s not possible to turn back the clock, ” TSMC founder Morris Chang told a Taiwanese tech association in October. “ If you want to re-establish a complete semiconductor supply chain in the United States, you will not find it to be a possible task, even after you spend hundreds of billions of dollars. ”
The federal money on the table is just a fraction of what the U.S. industry needs. And some executives are already wary of how governments are asserting themselves by slapping down mergers, limiting exports or banning working with industry partners.
The most recent example was Germany’ s nixing of Taiwanese company GlobalWafer’ s takeover of German rival Siltronic earlier this year. Industry officials say the move showed the West is turning inward when governments should develop stronger alliances with Asia.
The White House has quietly moved to stop Dutch company ASML Holding NV from exporting its cutting-edge equipment to China. ASML has an effective monopoly on advanced extreme ultraviolet lithography machines used by companies like TSMC.
The Trump administration began pressuring the Dutch government as early as 2018 not to authorize the sale of ASML’ s EUV machines to China, according to people familiar with the talks. That pressure has escalated under Biden, with officials considering pushing the Dutch government to put in writing the de-facto export ban, according to people familiar with the internal deliberations.
The company has become increasingly frustrated with the intervention of the U.S., which is also debating whether to ask the Dutch to ban ASML from selling its mature deep ultraviolet lithography systems to China. “ Any suggestion by any country to limit the shipment of the production equipment for mature technology to areas of the world where that technology is being produced is not a good idea, ” said ASML CEO Peter Wennink. “ We should not do that. ”
The U.S. and Europe will discuss their strategies on semiconductors as part of the Trade and Technology Council, but there’ s still a long way to go to figure out if and how to coordinate government aid in the most strategic ways. A U.S. official said they want to avoid a subsidies arms race, though a lingering mistrust from the Donald Trump years has made the EU wary.
While American eyes are on China, the EU plans to add strings to subsidies that would ensure the bloc has the essential components in times of emergencies. These ideas follow lessons from the pandemic, when the U.S. and U.K. had quicker access to vaccines. EU Internal Market Commissioner Thierry Breton has said the U.S.’ s Defense Production Act was a source of inspiration for the “ security of supply ” proposals.
The plans are not protectionist, nor are they seeking to make Europe completely autonomous, he said. Instead, they give the EU leverage to compete. “ That’ s the new geopolitics of supply chains, ” Breton said.
There’ s no shortage of skepticism, considering the EU tried to double production nearly 10 years ago and failed. Now, the overall goal is for Europe to make 20% of the world’ s semiconductors by 2030. With global demand expected to as much as double, in practice that means quadrupling Europe’ s production within eight years.
This time, the EU opened the door to providing public money for production of chips — a massive shift. But many companies in the region question whether the bloc should be placing so much weight on making the next generation of chips rather than the less advanced, more “ mature ” chips currently in shortage.
NXP CEO Sievers said the bloc should focus on providing first what the industry needs now. “ Right away leapfrogging to leading edge only, I think would be missing the beat of what the European industry needs in the next couple of years, ” he said.
Whatever type of chips end up being produced, industry insiders expect the U.S. and Europe will always be dependent on Asia for their materials, not least because of the global intricacies of supplies.
TSMC Chairman Mark Liu highlighted the connectivity in December, saying that some semiconductor chemicals required by Intel are shipped to the U.S. by Taiwanese suppliers. In other words, even American-made products rely on the outside world.
That’ s what makes the plans by Washington and Brussels so unrealistic, said Jan-Peter Kleinhans, a researcher at the German thinktank Stiftung Neue Verantwortung in Berlin.
There’ s also the risk of exacerbating shortages if you have politicians telling companies to prioritize certain chips for certain regions, Kleinhans said. “ Suddenly, it’ s not up to the market anymore, ” he said. Governments aren’ t chip buyers or chip makers. “ It’ s really 20th century policy tools applied to a 21st century value chain. ” | general |
When Will the Chip Shortage End? U.S., EU Spend Billions in Race to Beat China | Magdeburg in former East Germany is famous for its towering gothic cathedral, and not a lot else. It’ s now about to play a key role in U.S. and European efforts to tilt the global balance of power.
Intel Corp. unveiled plans on March 15 to build a giant, 17 billion-euro ( $ 18.7 billion) factory making cutting-edge semiconductors in the city, adding to new plants in Arizona and Ohio the company announced over the past six months.
They are part of Chief Executive Officer Pat Gelsinger’ s plan to wrest control of production from Asia and tackle the global shortage of chips exacerbated during the COVID-19 pandemic and exposed again following Russia’ s invasion of Ukraine. “ The situation reinforces why we’ re doing this project, and the need for globally resilient and balanced supply chain, ” Gelsinger said after revealing the Magdeburg site.
His ambition is one that the U.S. and European Union are promising to back with a combined $ 100 billion in a subsidy race to reduce reliance on imports just as China plans to turn itself into a chip powerhouse. Behind closed doors, though, some people in the industry are getting increasingly concerned that the push to make the West more competitive might backfire.
Their worry is not only that the money will be too little, too late, but the political strings attached to the aid may complicate global supply chains further. Different parts of the planet will compete to secure supplies while championing domestic plants that can’ t yet fill the void.
The dearth of semiconductors has brought some car manufacturing to a halt and delayed shipments of game consoles and smartphones, waking Washington and Brussels up to the fact that their continents are dependent on a handful of regions for the key parts. The most notable is Taiwan, a geopolitical hotspot because of historically tense relations with China and one whose vulnerability is under more scrutiny since Russia’ s invasion of its smaller neighbor.
Yet, however dysfunctional it may look at the moment, the supply chain is global and fully integrated. Unpicking it could carry greater risks, said Rudi De Winter, CEO of German chip maker X-Fab Silicon Foundries.
The semiconductor industry “ is a very global business, and it has done well being a global business, ” he said. “ This whole trend of trying to make things sovereign in every region and having its own supply chain is rather driven by politics and not by the semiconductor industry. ”
Russia, which has been sanctioned by the U.S. and Europe, now is a clear example of how semiconductors have become increasingly important political tools. The items were some of the first goods that Washington and Brussels targeted to cut Russia off from the global economy, and they’ ve continually threatened more action. Manufacturing of cars in Russia, for example, has already been hit.
On the flip side, Russia and Ukraine export palladium and neon used to make semiconductors, though chipmakers have downplayed the potential impact.
U.S. Secretary of Commerce Gina Raimondo said in an interview on March 9 that if Chinese companies defy U.S. restrictions against exporting to Russia, Washington could shut down companies by cutting them off from the American equipment and software they need.
Semiconductors and other high-tech are becoming “ weaponized ” with the current trade wars and supply chain issues, said Rafael Laguna de la Vera, CEO of SPRIN-D, Germany’ s federal agency for disruptive innovation. “ This is why regions need to invest into high tech to get resilient, ” he said.
The U.S. and Europe want to claw back their share of the chip market after collapses in recent decades. The U.S. accounted for nearly 40% of the world’ s silicon wafer production in the 1990s, while the EU accounted for more than 20%, according to figures cited by Washington and Brussels. The U.S. is now below 15% and the EU has about 10%.
In an effort to shift production away from Asia, President Joe Biden plans to put $ 52 billion into domestic semiconductor research, development and production as part of its broad China competition bill, though it is still awaiting approval. The EU’ s 27 member states, meanwhile, are only just scrutinizing the European Commission’ s recent proposal worth $ 48 billion to build up the bloc’ s chip capacity.
China has already been spending what could amount to $ 150 billion by 2030 to jumpstart production. The country is still far behind, especially when it comes to advanced chip making, but it’ s catching up quickly.
“ We’ re laser-focused on revitalizing America’ s semiconductor industry, ” Raimondo said at Intel’ s new site in Ohio in January. “ Semiconductors are the essential building blocks of our modern economy. ”
Some members of Congress, though, want to see the taxpayer funds attached to guardrails that prevent companies from using the money to invest in China while Intel at one point lobbied against the taxpayer funds going to firms headquartered abroad.
In the past, things were simple for chip producers, said Kurt Sievers, CEO of Dutch chipmaker NXP Semiconductors NV. Companies “ could just choose production locations and R & D locations wherever you wanted, ” he said. “ But I think we just have to stay realistic: Maybe these times are over. Now we are dealing with the world as it is going to evolve. ”
Intel CEO Gelsinger is a major force behind government investment in new plants. Despite the naysayers, he believes public funding could help Intel lower the cost of trying to catch up on cutting-edge chips after falling behind Taiwan Semiconductor Manufacturing Co., known as TSMC, and South Korea’ s Samsung Electronics Co. It would also make the U.S. and Europe more self-reliant.
“ Let’ s not waste this crisis, ” Gelsinger told Bloomberg earlier this year. “ It’ s good economics, but it’ s also national security. ” Intel’ s new plant in Magdeburg, which will start production in 2027, is part of an 80 billion-euro package of investment in Europe by the Californian company.
Whether the numbers stack up remains to be seen. The U.S. and Europe have some serious catching up to do, said SPRIN-D’ s de la Vera. Japan, for example, is also promising state aid to boost production. New facilities include a $ 7 billion factory planned by TSMC in conjunction with Sony Group Corp. and Denso Corp.
South Korea also wants to become the world’ s biggest chip producer, with companies and the government pouring a total $ 450 billion into the industry by 2030.
Achieving economies of scale that can compete with Taiwan’ s business model is also going to be tough if each region is racing to build its own capacity. TSMC accounts for more than 50% of the global foundry market, or the business of purely making chips for other companies. Its customers include Apple Inc., which relies on Taiwanese chips for iPhones.
Indeed, the reliance on TSMC is the core concern: an invasion of the island by China would leave the world’ s most advanced chips in the hands of Beijing. U.S. academic Jared McKinney recently suggested in a U.S. Army journal that Taiwan should protect itself by threatening to destroy chipmaking facilities so that Beijing would see its tech industry “ immobilized ” should it invade. He called it a “ broken nest ” strategy.
TSMC will have a new U.S. location operating in Arizona in two years and is now mulling a potential plant in Germany after European carmakers repeatedly expressed concerns about the impact from the chip shortage. But Taiwanese industry insiders remain skeptical of plans to relocate production back to the West.
“ It’ s not possible to turn back the clock, ” TSMC founder Morris Chang told a Taiwanese tech association in October. “ If you want to re-establish a complete semiconductor supply chain in the United States, you will not find it to be a possible task, even after you spend hundreds of billions of dollars. ”
The federal money on the table is just a fraction of what the U.S. industry needs. And some executives are already wary of how governments are asserting themselves by slapping down mergers, limiting exports or banning working with industry partners.
The most recent example was Germany’ s nixing of Taiwanese company GlobalWafer’ s takeover of German rival Siltronic earlier this year. Industry officials say the move showed the West is turning inward when governments should develop stronger alliances with Asia.
The White House has quietly moved to stop Dutch company ASML Holding NV from exporting its cutting-edge equipment to China. ASML has an effective monopoly on advanced extreme ultraviolet lithography machines used by companies like TSMC.
The Trump administration began pressuring the Dutch government as early as 2018 not to authorize the sale of ASML’ s EUV machines to China, according to people familiar with the talks. That pressure has escalated under Biden, with officials considering pushing the Dutch government to put in writing the de-facto export ban, according to people familiar with the internal deliberations.
The company has become increasingly frustrated with the intervention of the U.S., which is also debating whether to ask the Dutch to ban ASML from selling its mature deep ultraviolet lithography systems to China. “ Any suggestion by any country to limit the shipment of the production equipment for mature technology to areas of the world where that technology is being produced is not a good idea, ” said ASML CEO Peter Wennink. “ We should not do that. ”
The U.S. and Europe will discuss their strategies on semiconductors as part of the Trade and Technology Council, but there’ s still a long way to go to figure out if and how to coordinate government aid in the most strategic ways. A U.S. official said they want to avoid a subsidies arms race, though a lingering mistrust from the Donald Trump years has made the EU wary.
While American eyes are on China, the EU plans to add strings to subsidies that would ensure the bloc has the essential components in times of emergencies. These ideas follow lessons from the pandemic, when the U.S. and U.K. had quicker access to vaccines. EU Internal Market Commissioner Thierry Breton has said the U.S.’ s Defense Production Act was a source of inspiration for the “ security of supply ” proposals.
The plans are not protectionist, nor are they seeking to make Europe completely autonomous, he said. Instead, they give the EU leverage to compete. “ That’ s the new geopolitics of supply chains, ” Breton said.
There’ s no shortage of skepticism, considering the EU tried to double production nearly 10 years ago and failed. Now, the overall goal is for Europe to make 20% of the world’ s semiconductors by 2030. With global demand expected to as much as double, in practice that means quadrupling Europe’ s production within eight years.
This time, the EU opened the door to providing public money for production of chips — a massive shift. But many companies in the region question whether the bloc should be placing so much weight on making the next generation of chips rather than the less advanced, more “ mature ” chips currently in shortage.
NXP CEO Sievers said the bloc should focus on providing first what the industry needs now. “ Right away leapfrogging to leading edge only, I think would be missing the beat of what the European industry needs in the next couple of years, ” he said.
Whatever type of chips end up being produced, industry insiders expect the U.S. and Europe will always be dependent on Asia for their materials, not least because of the global intricacies of supplies.
TSMC Chairman Mark Liu highlighted the connectivity in December, saying that some semiconductor chemicals required by Intel are shipped to the U.S. by Taiwanese suppliers. In other words, even American-made products rely on the outside world.
That’ s what makes the plans by Washington and Brussels so unrealistic, said Jan-Peter Kleinhans, a researcher at the German thinktank Stiftung Neue Verantwortung in Berlin.
There’ s also the risk of exacerbating shortages if you have politicians telling companies to prioritize certain chips for certain regions, Kleinhans said. “ Suddenly, it’ s not up to the market anymore, ” he said. Governments aren’ t chip buyers or chip makers. “ It’ s really 20th century policy tools applied to a 21st century value chain. ”
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Smithfield Foods, Bumble Bee among companies joining Consumer Brands Association | UPDATE: March 16, 2022: The Consumer Brands Association said Wednesday several food companies are joining the organization, including meat processor Smithfield Foods, almond producer Blue Diamond Growers, tuna and seafood producer Bumble Bee Foods and J & J Snack Foods.
Two years after rebranding from the Grocery Manufacturers Association and overhauling its priorities, the CBA said it has seen a 35% increase in membership. The trade group currently represents 73 CPG companies covering nearly 2,000 brands from across industry sectors such as food and beverage products, cleaning and personal care.
`` Everyone in Washington — and even companies in our own industry — was ready to proclaim our association dead, ” Geoff Freeman, president and CEO of the CBA, said in a statement. “ But there was a clear need to build an organization that this essential industry deserves. ''
When Geoff Freeman became the president and CEO of the then-GMA in August 2018, there were a lot of changes needed to be made to restore the trade group to the position it once had.
In decades past, the group had the clout of the entire CPG food and beverage industry. It became the preeminent group representing those who made what people ate and drank, and had lobbied for the creation of the Food and Drug Administration, helped develop UPC symbols and piloted SmartLabel.
But as the group started to work against more transparent labeling policies about five years ago, it alienated several members. Campbell Soup was the first to leave the group, with then-CEO Denise Morrison saying at the 2017 Investor Day that the decision was based on `` purpose and principles '' dealing with consumer transparency.
`` We had the experience of finding ourselves at odds with some of the positions, '' she said.
Soon after, the floodgates opened, though many of the companies that left the trade group didn't give their reasons. Nestlé and Dean Foods, which was then the nation's largest dairy producer, were the next to drop out. Mars also left the group in 2017, telling Politico the company could `` more effectively drive our business objectives and meaningful progress for our categories and consumers by working with other like-minded companies and through other sector-specific trade associations and collaborations. '' Weeks later, Tyson and Unilever left the group, soon followed by Hershey and Cargill, then Kraft Heinz and the former DowDuPont.
Freeman brought a new attitude to the trade group. Instead of focusing on divisive things like individual ingredients and nutritional issues, he said in a 2019 interview with Food Dive that he would instead use the group to take action on the big issues everyone could agree on. The group's priorities became smart regulation, supply chain issues, building and maintaining consumer trust and sustainability. The pivot continued with CBA's new name, which officially change in 2020. When the name change was announced, Freeman said in an interview it was changed to be more inclusive, since household brands are also members, as well as clearly show the issues the group tackled would not only be food-and-beverage-centric.
Recently, the group has been much less controversial. Major initiatives include quantifying the impact of the CPG industry, which is responsible for one in 10 U.S. jobs, putting forward policy proposals and research on recycling, lobbying for policies that kept manufacturers in business amid the COVID-19 pandemic, pushing for clear and uniform federal regulations on CBD and advocating for food manufacturers to have priority in COVID-19 vaccinations.
In the 2019 interview with Food Dive, Freeman said his goal for the organization was to build a group that had extraordinary value for its members. He said he was confident there would be no more high profile departures. Campbell Soup is the first high-profile return. In a statement about the return emailed to Food Dive, Campbell Soup said, `` Consumer Brands is driving a focused, consumer-centric agenda that aligns well with Campbell’ s goals, and we look forward to contributing to the direction of the association during this pivotal time for the industry. ''
Even with the return of Campbell Soup, there is still a ways for CBA to go — in 2017, the group had about 250 members and today it has more than 100 — but the breach may be on its way to being repaired.
In 2019, Freeman told Food Dive he had spoken with every company that had left the trade group, as well as those that had never joined.
`` There's no doubt that there are hard feelings out there and it's going to take time and we're gon na have to prove that we are who we say we are, '' Freeman said then. `` But I can tell you that I have, based on the conversations I 've had, I am extremely confident that when we demonstrate that we can deliver on this new value proposition, you will see a [ CBA ] membership that is broader, more diverse and more united than you 've ever seen it before. ''
Clarification: A previous version of this story referred only to the number of the group's current CPG members instead of all three membership categories, which also includes retailers and allied members.
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China Boosts Bed Spaces As Omicron Outbreak Spreads | China has moved to free up hospital beds as officials on Wednesday reported thousands of new cases from an Omicron-led coronavirus outbreak that has put millions under lockdown and raised fears for the health system.
The country recorded 3,290 new Covid-19 cases on Wednesday, including 11 severe cases.
The total was down on Tuesday's count of more than 5,000, but the highly transmissible variant is posing the sternest challenge yet to China's 'zero-Covid ' strategy to contain the pandemic.
China, where the first virus case emerged in Wuhan in late 2019, has not officially reported any Covid-related deaths for more than a year.
Under strict Covid-19 protocols, the country previously sent all patients with any symptoms to specialist hospitals.
But a steep jump in cases, which has led to the 17.5 million residents of the southern tech hub of Shenzhen being locked down and restrictions imposed on Shanghai and other cities, has driven concerns over looming bed shortages.
The National Health Commission late Tuesday said patients with mild Covid cases could isolate at a central quarantine facility to ease pressure on hospitals.
`` Patients with Omicron variant strains are mainly asymptomatic infections and mild cases, most of them do not require serious treatment, '' the health authority said.
`` All admission to designated hospitals will take up a lot of medical resources. ''
Images of patients lying on gurneys outside hospitals in Hong Kong, where hospitals have been overrun by a surge in cases, have spooked mainland officials, who are now also rushing to build makeshift hospitals in some provinces.
Footage on state broadcaster CCTV Wednesday showed dozens of giant cranes assembling `` temporary hospitals '' in northeast China's Jilin province, which has reported more than 5,000 cases over the past week.
The province of more than 24 million residents has only 22,880 hospital beds.
As of Tuesday, 6,000 railway carriage-style hospital rooms -- first erected during the early days of the pandemic in Wuhan -- have been put in place in Jilin City and the nearby metropolis of Changchun, to deal with a feared influx of patients. | business |
Israel Records New Covid Variant | Israel's ministry of health said Wednesday it had recorded two cases of new Covid variant, but which officials said they were not unduly worried about.
The strain, combining two sub-variants of the Omicron version of the Covid-19 virus -- dubbed BA.1 and BA.2 -- was recorded during PCR tests on two passengers arriving at Israel's Ben Gurion airport.
`` This variant is still unknown around the world, '' the ministry statement read.
`` The two cases of the combined strain, which have been discovered so far, suffered from mild symptoms of fever, headaches and muscle dystrophy, and do not require a special medical response, '' it added.
Israel's pandemic response chief, Salman Zarka, played down the risks.
`` The phenomenon of combined variants is well known, '' Zarka told Army Radio. `` At this stage, we are not worried about it leading to serious cases ''.
More than four million people out of Israel's population of 9.2 million have received three coronavirus vaccine shots.
A total of almost 1.4 million cases of Covid infection, including 8,244 deaths, have been officially recorded in the country.
Last month, Israel announced that unvaccinated tourists would be allowed to enter as part of an easing of covid restrictions.
The country was seeing a `` consistent decline in morbidity data, '' Prime Minister Naftali Bennett said.
A previous effort to reopen the border last November foundered after just a few weeks because of the fast-spreading Omicron variant.
Israel was one of the first countries to launch a national vaccination campaign in December 2020. | business |
Editor's letter: Feeling the squeeze | You are currently accessing Investment Week via your Enterprise account.
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Many believed the threat of stagflation was a misnomer, however, with LFDE CIO Olivier de Berranger telling Investment Week in October last year that the backdrop was `` completely different '' from when we last suffered stagflation in the 1970s and 1980s.
`` Inflation has been caused by this strong demand in an environment of temporary supply constraints in the aftermath of the Covid-19 crisis. And global economic growth is forecast at 4.5% for 2022, after close to 6% this year, which hardly qualifies as stagnation, '' he said.
In the same article, Royal London AM's head of rates and cash Craig Inches argued we would not see stagflation `` because we are not going to see zero or negative growth over the next few years '' and that `` growth will actually be quite robust ''.
As the industry began to position itself for a world in which there was prolonged inflation, but where the economy continued to recover from the Covid-19 pandemic, a black swan event and humanitarian crisis hit: Russia invaded Ukraine.
Brent crude oil, which had already reached historic highs due to supply chain squeezes, reached an eye-watering $ 139 per barrel last week as the US and the UK confirmed they would ban and phase out Russian oil, gas and coal imports. Meanwhile, the EU has announced it will cut its gas imports from the country by two thirds over the next 12 months.
Susannah Streeter, senior investment and markets analyst at Hargreaves Lansdown, said the UK and US's ban of Russian energy exports will have a `` ricochet effect on their economies… pushing up prices for industries across the board and making the cost of living crisis even more painful ''.
And while Russia produces 12 million of every 100 million barrels of oil around the world on a daily basis, it is also a major producer of crops, with Russia and Ukraine accounting for 30% of global wheat exports according to research from Schroders.
This comes at a time when climate change is already weighing heavily on food production, with research from PNAS warning that corn and wheat yields will fall by 14% and 12% respectively even under a 2°C of warming scenario and not taking the Ukraine crisis into account.
Even more dire supply chain squeezes on both commodities and food suggest we are not out of the stagflationary woods yet.
Henk-Jan Rikkerink, global head of solutions and multi asset at Fidelity, said: `` We think higher commodity prices are here to stay and will lead to both higher inflation and lower growth, meaning the risk of outright recession in Europe is rising sharply, especially if physical commodity flows from Russia are substantially disrupted. The challenges facing US, UK and European monetary policymakers have become more complicated. ''
Streeter agreed, adding that central banks are `` faced with the increasingly difficult tightrope to tread of trying to bring down inflation by raising rates, which will make overall costs more unbearable, potentially tipping economies back into a downturn ''.
© Incisive Business Media ( IP) Limited, Published by Incisive Business Media Limited, New London House, 172 Drury Lane, London WC2B 5QR.Registered in England and Wales with company registration numbers 09177174 & 09178013 | business |
Antibody durability at 1 year after Sputnik V vaccination - The Lancet Infectious Diseases | Antibody waning against SARS-CoV-2 over time after vaccination, together with the emergence of new viral variants, pose great challenges for ending the pandemic. To our knowledge, no previous work has assessed the long-term prevalence of anti-SARS-CoV-2 antibodies in individuals vaccinated with Sputnik V ( Gam-COVID-Vac).1Logunov DY Dolzhikova IV Shcheblyakov DV et al.Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia.Lancet. 2021; 397: 671-681Google Scholar We assessed the persistence of anti-spike IgG antibodies and their neutralising capacity against the original SARS-CoV-2 lineage ( B.1) and a local isolate of the BA.1 lineage of the omicron ( B.1.1.529) variant in a longitudinal cohort during 1 year after Sputnik V vaccination in Argentina.
We used 400 paired serum samples ( 100 samples at each timepoint, including at baseline before vaccination) from 100 volunteers who received two doses of Sputnik V that were obtained between Jan 1, 2021, and Jan 15, 2022. Participants with current or previous SARS-CoV-2 infection, determined by assessing seropositivity to nucleocapsid protein, were excluded from the analysis. The geometric mean ( GM) of international units of IgG anti-spike antibodies2Ojeda DS Gonzalez Lopez Ledesma MM Pallarés HM et al.Emergency response for evaluating SARS-CoV-2 immune status, seroprevalence and convalescent plasma in Argentina.PLoS Pathog. 2021; 17e1009161Google Scholar per mL ( IU/mL) were 994 ( 95% CI 769–1285) at 42 days, 80 ( 60–106) at 180 days, and 36 ( 27–47) at 360 days after completion of the two-dose vaccination scheme ( figure A; appendix p 2). Overall, a 27-fold reduction in IgG was observed 1 year after Sputnik V vaccination.FigureLongitudinal analysis of humoral response up to 1 year after two doses of Sputnik V vaccineShow full caption ( A) IgG anti-spike antibody concentrations quantified according to the WHO International Standard. Antibodies were measured at 42 ( n=100), 180 ( n=100), and 360 ( n=100) days after completion of the two-dose vacination schedule. ( B) Neutralising titres measured at 50% inhibition against the pseudotyped virus ( CoV2pp GFP) for the same cohort as in panel A. Each datapoint indicates one volunteer, the horizontal lines at each timepoint show the mean titre, with error bars showing 95% CIs. Wilcoxon matched-pair test was used.View Large Image Figure ViewerDownload Hi-res image Download ( PPT)
( A) IgG anti-spike antibody concentrations quantified according to the WHO International Standard. Antibodies were measured at 42 ( n=100), 180 ( n=100), and 360 ( n=100) days after completion of the two-dose vacination schedule. ( B) Neutralising titres measured at 50% inhibition against the pseudotyped virus ( CoV2pp GFP) for the same cohort as in panel A. Each datapoint indicates one volunteer, the horizontal lines at each timepoint show the mean titre, with error bars showing 95% CIs. Wilcoxon matched-pair test was used.
We assessed the GM half-maximal neutralising titre ( GMT, IC50) using a pseudotyped vescicular stomatitis virus carrying the spike of a viral isolate from Wuhan at the early stage of the pandemic ( appendix p 4). The GMT at 42 days after vaccination was 133 ( 95% CI 92–193), at 180 days was 28 ( 19–39), and at 360 days was 11 ( 8–16; figure B).
Considering previous studies indicating that antibody responses undergo a maturation process,3Schmidt F Muecksch F Weisblum Y et al.Plasma neutralization of the SARS-CoV-2 omicron variant.N Engl J Med. 2022; 386: 599-601Google Scholar, 4Gruell H Vanshylla K Tober-Lau P et al.mRNA booster immunization elicits potent neutralizing serum activity against the SARS-CoV-2 omicron variant.Nat Med. 2022; ( published online Jan 19.) https: //doi.org/10.1038/s41591-021-01676-0Google Scholar we analysed the serum neutralising activity over time against the omicron variant. To this aim, we assessed the neutralising activity elicited by the Sputnik V vaccine5Gonzalez Lopez Ledesma MM Sanchez L Ojeda DS et al.Longitudinal study after Sputnik V vaccination shows durable SARS-CoV-2 neutralizing antibodies and reduced viral variant escape to neutralization over time.mBio. 2022; ( published online Jan 25.) https: //doi.org/10.1128/mbio.03442-21Google Scholar using the original B.1 isolate and a local isolate of BA.1 omicron. For this analysis, we used 60 samples ( 20 samples per timepoint) with the highest neutralising GMT for the original B.1 virus. For all timepoints analysed, we found a substantial decrease in the serum neutralising capacity against the omicron variant compared with the B.1 lineage ( 64-fold reduction at 42 days, 32-fold reduction at 180 days, and 28-fold reduction at 360 days after vaccination; appendix p 2). Six ( 30%) of the 20 immunised individuals remained positive for neutralising antibodies against omicron at 42 days after vaccination. This proportion increased to 45% ( nine of 20) at 360 days. Similar results have been obtained using other vaccines against SARS-CoV-2. Studies in individuals vaccinated with mRNA vaccines reported a similar decrease at 6 months after vaccination in both the concentration of IgG antibodies directed to the spike protein and the serum neutralising capacity against the original B.1 variant.6Levin EG Lustig Y Cohen C et al.Waning immune humoral response to BNT162b2 COVID-19 vaccine over 6 months.N Engl J Med. 2021; 385: e84Google Scholar, 7Naaber P Tserel L Kangro K et al.Dynamics of antibody response to BNT162b2 vaccine after six months: a longitudinal prospective study.Lancet Reg Health Eur. 2021; 10100208Google Scholar A substantial reduction in neutralising capacity against the omicron variant was also reported with mRNA vaccines.8Muik A Lui BG Wallisch AK et al.Neutralization of SARS-CoV-2 omicron by BNT162b2 mRNA vaccine-elicited human sera.Science. 2022; 375: 678-680Google Scholar
Overall, our data suggest that maturation of the antibody response observed over time after standard Sputnik V vaccination is unable to overcome the ability of omicron to escape the humoral response induced by the vaccine, emphasising the need to administer a booster dose urgently. Booster vaccination combining other vaccine platforms would be an option to further increase neutralising antibody levels against the omicron variant.
LS, SOR, MP, and DSO contributed equally. We declare no competing interests.
Download.pdf (.24 MB) Help with pdf files Supplementary appendix
Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in RussiaThis interim analysis of the phase 3 trial of Gam-COVID-Vac showed 91·6% efficacy against COVID-19 and was well tolerated in a large cohort. Full-Text PDF | tech |
Russia-Ukraine war triggers debate over weapons in ESG funds | You are currently accessing Investment Week via your Enterprise account.
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Two weeks into Putin's invasion of Ukraine - which gave up its arsenal of Soviet-made nuclear weapons in 1994 under the condition that Russia, the US and UK would essentially leave it alone - and the newsflow has been relentless.
Amid the sanctions, falling bombs and threats of nuclear war, inboxes have been flooded with predictions of the economic fallout and how financial markets will be affected - but it is all guesswork.
As Royal London CEO Barry O'Dwyer told Investment Week, `` the secondary consequences '' of war in Ukraine `` are yet to be known ''.
At the time of writing ( 10 March), there was no sign of de-escalation in sight. `` Nobody knows how long it will go on for, '' O'Dwyer said.
The military-industrial complex marches on. Weapons sales reached a record level of $ 531bn in 2020 while most the world was locked down under Covid-19 rules, according to the Stockholm International Peace Research Institute.
Throughout 2021, flows into nearly 500 global funds with between 5% and 70% of their holdings invested in controversial weapons were steady overall at net $ 13.1m. In January this year alone, inflows soared to net $ 792m, Morningstar data shows. Overall assets invested in the funds stood at over $ 600bn.
From January 2012 to 28 February 2022, returns across the funds included in the research averaged 9.75%.
Out of these funds, just three are explicitly labelled as ESG, with allocation to controversial weapons ranging from about 7% to over 9%.
The New York Times reported on 3 March that the war in Ukraine prompted a pitch for'socially responsible ' military stocks, while Swedish financial firm Skandinaviska Enskilda Banken AB is set to allow some of its funds to buy shares of weapons manufacturers and defence companies, despite pledging the contrary just one year ago as part of its so-called ESG principles.
Meanwhile, Citi analysts Charles Armitage and Samuel Burgess told the paper recently that weapons makers are `` defending the values of liberal democracies and creating a deterrent, which preserves peace and global stability '', and should therefore be included in ESG-labelled investment funds.
Research by financial services firm Jeffries noted how ESG-focused investors have historically excluded companies with revenues derived from `` defence activities ''.
`` Regulatory tailwinds, geopolitical concerns and a structural change in national defence spending could alter this dynamic, '' the firm said, arguing that the sector `` could be deemed investable '' in the medium to long term.
According to Jeffries, unfolding geopolitical tensions `` have highlighted a need for national defence spending ''.
`` Concerns around reduced defence budgets have largely been allayed. This likely provides structural growth potential for the sector in the medium term. Regulatory changes, such as the inclusion of nuclear power, could also provide tailwinds for the sector, '' the firm stated.
Morningstar investment analyst Nicolo Bragazza argued: `` As war erupts, it is normal for investors to think of defence stocks as a natural buy. However, in times of elevated uncertainty, it is important to stick to fundamentals and to avoid decisions based on emotions. ''
However, Bragazza noted that although weapons and civilian firearms are usually avoided in ESG funds, `` defence may be considered as a public good and some weapons may be used for defensive purposes rather than to attack ''.
He continued: `` After all, it is one of the main duties of the State to defend its citizens and citizens pay taxes to get protection and security in return. Therefore, there is not a simple answer to whether defense stocks should be included in ESG portfolios. ''
According to Patrick Wood Uribe, CEO of machine learning-driven data provider Util, these latest ‘ greenwashing ' developments in the ESG space are unsurprising.
`` Anything can be an ethical stock so long as it is on track to make a lot of money, '' he said.
`` Given the inconsistency and subjectivity of existing sustainability data, it is not hard to find anecdotal justifications for exposure to stocks that do not, on the face of it, look virtuous. ''
Like many arms companies, the world's biggest weapons producer Lockheed Martin, has a page dedicated to ESG and sustainability on its website. Some companies within the weapons sector have also been actively involved in developing climate change mitigation technology.
According to Jeffries, these factors could `` trigger '' renewed interest from investors across the board, including ESG and `` socially-minded '' funds.
`` Companies with significant climate mitigation exposure could see further interest from ESG investors, '' the firm suggested.
BAE Systems, which has played a major role in supplying Saudi Arabia with the wares for its ongoing war in Yemen, has openly committed to achieving net zero scope 1 and 2 emissions by 2030.
CEO Charles Woodburn had previously said: `` Sustainability is important to us and our stakeholders. The long-term outlook for the company and the defence sector means we need to anticipate change and ensure we continue to improve on what we do today. ''
Util's Uribe argued: `` Every company can have both positive and negative outcomes. Weapons manufacturers are no exception. Acknowledging nuance exists, however, does not detract from the millions of deaths for which the industry is responsible.
According to Uribe, the social and environmental `` merits '' of controversial industries such as weapons can be understood by leveraging big data and machine learning. `` The bad news is it is still up to us to decide what we want to do with that knowledge, '' he said.
For Henrik Pontzen, head of ESG at Union Investment, there is no debating the matter.
`` Since Russia's most recent war of aggression in Ukraine, there has been a broad political consensus among NATO members and other European countries that higher defence spending will be necessary in future, '' he said.
`` But a necessity does not automatically imply sustainability. Sustainable investments must fulfil the criterion ‘ do no significant harm ' - this is not the case with armaments. ''
All the while, wars across the globe are ongoing, lining pockets.
© Incisive Business Media ( IP) Limited, Published by Incisive Business Media Limited, New London House, 172 Drury Lane, London WC2B 5QR.Registered in England and Wales with company registration numbers 09177174 & 09178013 | business |
Netflix Tests Charging A Fee To Share Accounts | Netflix on Wednesday said it is testing charging a fee to subscribers who share their accounts with people who don't live in their homes.
The US-based steaming service has long taken a relaxed approach to users sharing passwords with family or friends, but recently saw stock dive on quarterly results that showed cooling subscriber growth.
Competition in the streaming television market meanwhile has been ramping up, particularly from Disney+, with the cost of producing coveted original shows climbing as well.
In the coming weeks, Netflix will begin offering subscribers in Chile, Costa Rica and Peru the option to add as many as two people to `` sub-accounts '' at a monthly fee of $ 2 to $ 3, Netflix product innovation director Chengyi Long explained.
`` We recognize that people have many entertainment choices, so we want to ensure any new features are flexible and useful for members, whose subscriptions fund all our great TV and films, '' Long said in a blog post.
The Silicon Valley streaming titan has been working on ways for subscribers to share `` outside their household... while also paying a bit more, '' she said.
Netflix said it will allow people already sharing accounts to transfer profile and viewing history information to new sub-accounts.
Long said the company will study the utility of the new model in the three countries before making changes anywhere else.
Netflix ended last year with 221.8 million subscribers, just below target, after booming during coronavirus lockdowns that kept people at home and on the platform.
Things are not looking better for the first quarter of 2022, with the most recent Netflix earnings report saying the firm expected to add only 2.5 million subscribers.
Most of the 8.3 million subscriptions added at the end of last year came from outside North America, according to the streaming service. | business |
Cyber Security Takeover May Harm Competition: UK Regulator | US cyber security giant NortonLifeLock's planned purchase of Czech rival Avast for more than $ 8 billion risks harming competition and could face an in-depth probe, Britain's regulator warned on Wednesday.
The Competition and Markets Authority ( CMA) said in a statement that it had concerns over the deal, but NortonLifeLock expressed surprise at the news after winning clearance elsewhere.
The pair announced the blockbuster takeover last year to create a leading consumer business as internet activity boomed during the pandemic.
`` As the companies are close competitors, with few other significant rivals, the CMA is concerned that if completed the proposed deal could lead to a reduction in competition in the UK market, '' the regulator said in a brief statement.
`` This could lead to UK consumers getting a worse deal when looking for cyber safety software in the future. ''
Both companies have five days to submit proposals to address its concerns.
The CMA will then decide whether to launch an in-depth competition investigation.
The news sent Avast's share price slumping more than 11 percent in midday trade on the London stock market.
`` NortonLifeLock regards this decision as surprising, '' it said in a separate statement, adding the deal had already been cleared in Germany, Spain and the United States.
`` The parties believe that the merger can only benefit consumers across the globe, including in the UK, through increased innovation and greater consumer freedom and choice. ''
The US company `` remains confident '' that the deal would win approval.
Businesses worldwide are at threat from an increasingly lucrative form of digital hostage-taking, or ransomware attacks, that typically see hackers encrypting victims ' data and then demanding money for restored access.
At the same time, online activity exploded in popularity during the coronavirus pandemic and continues to boom. | business |
Global Electronic Component Shortage | Sourcengine is a global e-commerce marketplace for electronic components where customers can check over 20 million component offers and buy from 3,000+ traceable suppliers in one easy transaction. Procurement specialists can shop without ever…
On March 16, a 7.4 magnitude earthquake struck Northeast Japan, causing two fatalities, over 100 injuries, and leaving thousands of people without water and power. The disaster also significantly disrupted the country’ s manufacturers, including several chipmakers.
Renesas closed its Naka, Yonezawa, and Takasaki factories following the tremblor but partially reactivated the three sites on March 17. It reported no casualties or “ significant facility damage ” and said the Yonezawa plant would resume full production on March 20 while the Naka and Takasaki sites would restart on March 23. The vendor, like its contemporaries, has not disclosed the full impact of the event on its output.
DigiTimes noted the three fabs represent 40 percent of its overall capacity, and none of them produce auto chips.
Murata Manufacturing, a leading capacitor company, idled four factories after the earthquake struck and extinguished a fire at one facility. The firm has already restarted work at its Koriyama and Motomiya fabs and intends to bring its Tome and Sendai plants back to full utilization this week.
Sony paused operations at three domestic production complexes in the wake of the disaster. It plans to gradually resume work at its semiconductor laser, storage media, and image sensor production centers.
Kioxia shuttered its K1 Fab in Kitakami in the aftermath of the quake, pending an inspection. The plant is responsible for 8 percent of the manufacturer’ s overall output. TrendForce reports the facility, which operates with Western Digital, sustained partial wafer input damage. The market intelligence provider expects the affected factory’ s production yields will decrease in the first quarter due to tremblor.
Last month, Kioxia’ s Kitakami and Yokkaichi sites experienced a contamination incident that significantly reduced its flash memory supply. DigiTimes expects the corporation’ s 3D TLC NAND prices to rise by 15 percent and its MLC NAND bit rates by 5 percent soon.
Given the widespread nature of the disaster, other price changes and availability issues are likely coming soon.
Foxconn recently announced it partially resumed production in Shenzhen, China, under a “ closed-loop management process ” on March 16. The firm’ s solution involves transporting tens of thousands of workers directly between its dormitories and factories and regular COVID-19 testing. Its insulated system had enabled it to restart operations even when the city of 17.5 million remained under lockdown.
The Chinese government introduced new policies to balance its approach to the coronavirus pandemic with regional economic concerns.
Chinese officials first enacted the “ COVID zero ” protocol to curb new nationwide infection rates shortly after the pandemic began. International health authorities applauded the strategy for strictly limiting illnesses and deaths in-country. However, widespread semiconductor production stoppages in the country’ s industrial core played a big role in cultivating the global chip shortage.
Local leaders eventually lifted the lockdowns once the nation’ s case numbers plummeted. But quarantine mandates returned earlier this month when the nation’ s infection rates reached their highest levels in two years. Last Wednesday, Beijing allowed Foxconn to bring its second-largest manufacturing campus back online to mitigate lockdown-related financial fallout.
The government also lifted lockdowns on multiple areas in the Guangdong province because they reported no new COVID cases for several days. That said, China reported 4,100 new coronavirus infections last Thursday, with 105 coming from Shenzhen.
Consequently, the country’ s latest COVID flareup, and its impact on many local chipmakers, is still an unfolding crisis.
DRAM will become more expensive later this year due to the ongoing impact of the global chip shortage.
DigiTimes found spot DRAM prices have risen 5 to 7 percent in Q1 2022, while contract rates fell by 7 to 9 percent. However, the publication believes the component type will experience an across-the-board cost jump in the second quarter. It attributes the change to the priorities of the semiconductor industries memory chip manufacturers. At present, the field’ s leading vendors are committed to refining their process technology to improve their yields.
But that means top DRAM manufacturers are directing funding away from production capacity expansion, limiting their output. Until the bottleneck within the segment is resolved, prices will probably continue climbing.
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Here’ s Why Diversifying Your Electronic Component Suppliers is More Important Than Ever This white paper details why the last few years introduced an unprecedented level of disruption into the electronic components supply chain, and how OEMs can better address present and future challenges by embracing supplier diversification. Download Now! | general |
Supply Chain Visibility: 5 Questions You’ re Probably Asking - Materials Handling Virtual Summit | The COVID-19 pandemic has touched every industry. For supply chains, it has demonstrated the importance of end-to-end visibility. As a supply chain professional, you understand the landscape is evolving. First, it is no longer sufficient to simply track and trace a shipment. Second, you must be able to make effective, real-time decisions, even during a disruption. The challenge? Only a small fraction of companies believe that they’ ve achieved total supply chain visibility. Fortunately, visibility improvements — big or small — are easier to achieve than you may think. Download this doc for answers to some of the top questions supply chain professionals are asking when it comes to greater visibility. Questions like: How granular a view do I need over my supply chain? Accurate ETAs are nice. But how else can visibility save me money? I only have basic visibility. What are the first practical steps towards more? Can I get more visibility with my existing tools? Can a platform approach help my company gain full visibility?
The COVID-19 pandemic has touched every industry. For supply chains, it has demonstrated the importance of end-to-end visibility. As a supply chain professional, you understand the landscape is evolving. First, it is no longer sufficient to simply track and trace a shipment. Second, you must be able to make effective, real-time decisions, even during a disruption.
The challenge? Only a small fraction of companies believe that they’ ve achieved total supply chain visibility. Fortunately, visibility improvements — big or small — are easier to achieve than you may think.
Download this doc for answers to some of the top questions supply chain professionals are asking when it comes to greater visibility. Questions like: | general |
UPS heralds partnership with Novavax for vaccine distribution and delivery efforts | Atlanta-based global transportation and logistics services provider UPS recently announced it has formed a partnership with Novavax, a global biotech company, focused on the distribution and delivery of Novavax’ recently-approved COVID-19 vaccine to 27 European Union countries.
UPS said that the new vaccine is another weapon in the global fight against COVID-19. And it explained that because it does not require ultra-cold refrigeration, it can be more easily delivered to remote and rural areas that don’ t have cold chain facilities. What’ s more, the company added that UPS Healthcare’ s European Network has been keenly focused on vaccine delivery efforts, with UPS having delivered more than 1 billion doses with 99.9% on-time delivery in more than 110 countries.
“ UPS is proud to partner with Novavax to distribute its COVID-19 vaccine in the European Union and beyond, ” said Wes Wheeler, president of UPS Healthcare, in a statement. “ The extensive infrastructure UPS Healthcare has built in the European Union to handle temperature-sensitive products will make this life-saving vaccine and other needed healthcare products quickly available to hundreds of millions of people. ”
A UPS spokesperson provided LM Group News Editor Jeff Berman an overview of the company’ s partnership with Novavax in the Q & A below.
UPS: We’ ve been supporting Novavax since the start of its vaccine journey—which was its first commercial product after spending the majority of their history as an R & D-focused firm.
They saw that we could support the organization through initial clinical trials and also take its vaccine from the lab to the patient’ s arms—greatly simplifying the process for them. To give you some context, through our UPS Healthcare subsidiary, Marken, we have supported more than 130 COVID-19 vaccine-related clinical trials to date—including nearly all vaccines and treatments in development and use today.
By collaborating so closely, we’ re able to understand each vaccine or treatment's specific needs and plan the transport networks well in advance—allowing us to ship them globally as soon as they were approved.
Once the Novavax vaccines were reviewed, approved, and ready to ship, UPS Healthcare provided access to over 500 newly mapped out trade lanes globally, as well new air and ground routes—essential for the transport of time-critical and temperature-sensitive vaccines. While in transit, the vaccine shipments are monitored 24/7 by three global 24/7 UPS Healthcare Command Centers, dedicated to ensuring on-time delivery, with contingency plans and solutions to mitigate the risks of extreme weather and other obstacles.
We’ re also investing in the latest technology. Last year we rolled out our UPS Premier service in Europe. As a technology-enabled express delivery service, this product upgrades small packages with advanced sensor technology and ensures a priority lane and tracking to within 10 feet of their location in our global network.
All in all, this meant we’ ve been able to deliver well over 1.2 billion vaccines, from all partner providers, to over 100 countries at 99.9% on-time delivery—a level of service we should all aspire to industry-wide.
UPS: When you look to the future of healthcare, it’ s all about innovations in biologics, specialty pharmaceuticals, and personalized medicine. These products make up the majority of the new products in development and are driving significant demand for precision logistics for what are patient-critical, time-and temperature-sensitive products.
We’ ve been investing in a network to meet those needs for a long time, building out a ‘ network within a network’ to make sure we provide the best quality healthcare service on the market. Our European Healthcare hub is run out of Roermond in the Netherlands, the facility is close to UPS’ s European air hub at Cologne Bonn Airport, and has direct access to major ports, including Rotterdam, Antwerp, and Amsterdam, allowing for short transit times across the world and next-day delivery to 80% of Europe. The hub is acting as our central distribution point for the Novavax vaccines.
Alongside this hub, we have an existing presence in some of the largest and quickest growing healthcare markets in the world, including the UK, Czech Republic, Spain, Poland, and Hungary. All give us giving us key pathways across the region to support traditional, fast-growing organizations and their customers.
As part of our aggressive global expansion strategy, we’ ve also just announced and will shortly bring online new facilities, including in Rome, Blonie ( PL), as well as our first dedicated Healthcare facility in Giessen, Germany. This adds to the new and upgraded facilities in Ostrava ( CZ), Budapest ( HU), and Roermond ( NL) that were completed last year. These state-of-the-art facilities will include multiple controlled temperature environments for healthcare products requiring -20C to -80C, 2C to 8C, and 15C to 25C storage.
We’ re also expanding our cold chain transportation services across the continent. These vehicles are capable of supporting transport healthcare products in temperature-controlled environments and offer next-day, GDP-compliant delivery for hospitals, pharmacies, clinics, laboratories, and doctors that are all increasingly relying on time-critical and temperature-sensitive treatments for their patients. We’ ve recently added these services to Belgium and certain regions in Italy, which complement our existing services in the Netherlands, Luxembourg, Hungary, the UK, and Poland.
UPS: The global market for biologic drugs ( like vaccines) is set to increase from $ 285.5 billion in 2020 to $ 421.8 billion by 2025—the opportunity is huge. As you can see through our partnership with Novavax, we can truly offer a one-stop-shop solution for our customers. From trials, manufacturing to last-mile delivery we have the expertise, scale, and quality network to support what is needed now and well into the future.
Strategic Real Estate. Applied Technology. Tailored Service. Creativity.… | general |
Innovate and Optimize to Beat Last-Mile Delivery Challenges - Materials Handling Virtual Summit | The COVID-19 pandemic has accelerated online retail worldwide by 5 years. This means growing online market share and revenue for both traditional retailers and native e-commerce providers, including Business-to-Consumer ( B2C), Direct-to-Consumer ( DTC) brands, and Business-to-Busines ( B2B). The percentage of global retail revenue attributed to e-commerce has increased from 10% in 2017 and is projected to double by 2022 to 20% as the pandemic accelerates this trend, originally anticipated to take another 5 years. This compressed transition has placed more pressure on transport operators worldwide, including last-mile providers. These fleets have to accommodate surging demand, along with increasing customer expectations for service. Concurrently, internal pressures remain to contain costs and streamline their operations. Globally, the local delivery telematics market is expected to grow by 17% from 2020 to 2025, according to ABI Research. However, too many businesses continue to use outdated systems and broken processes, lacking a seamless information flow. The challenges of last-mile delivery include shrinking delivery timelines, profitability concerns, scaling issues, and numerous evolving delivery options. It is critical that businesses fully optimize the final leg of the transportation journey, to not only materially reduce the estimated 50% total cost of delivery, but also to offer a consistent end customer experience, through visibility into accurate ETAs and clear communication and options for the customer. Download this paper to learn how you can innovate and optimize the challenges of last-mile delivery.
The COVID-19 pandemic has accelerated online retail worldwide by 5 years. This means growing online market share and revenue for both traditional retailers and native e-commerce providers, including Business-to-Consumer ( B2C), Direct-to-Consumer ( DTC) brands, and Business-to-Busines ( B2B). The percentage of global retail revenue attributed to e-commerce has increased from 10% in 2017 and is projected to double by 2022 to 20% as the pandemic accelerates this trend, originally anticipated to take another 5 years.
This compressed transition has placed more pressure on transport operators worldwide, including last-mile providers. These fleets have to accommodate surging demand, along with increasing customer expectations for service. Concurrently, internal pressures remain to contain costs and streamline their operations. Globally, the local delivery telematics market is expected to grow by 17% from 2020 to 2025, according to ABI Research. However, too many businesses continue to use outdated systems and broken processes, lacking a seamless information flow.
The challenges of last-mile delivery include shrinking delivery timelines, profitability concerns, scaling issues, and numerous evolving delivery options. It is critical that businesses fully optimize the final leg of the transportation journey, to not only materially reduce the estimated 50% total cost of delivery, but also to offer a consistent end customer experience, through visibility into accurate ETAs and clear communication and options for the customer.
Download this paper to learn how you can innovate and optimize the challenges of last-mile delivery. | general |
NRF issues bullish 2022 retail sales forecast | While there is more than a healthy share of uncertainty in logistics and the supply chain, one thing that remains certain, is the ongoing aggressive pace of United States retail sales activity, with consumers continuing to spend on whatever it is they may need, amid record-high gas prices, inflation, fears of a recession, and the Russia-Ukraine conflict, among other factors.
That was made clear in data issued by the Washington, D.C.-based National Retail Federation ( NRF) this week, in its 2022 retail sales forecast.
In its forecast, the NRF is calling for 2022 retail sales to see an annual increase between 6% -to-8%, coming in at between $ 4.86 trillion-to- $ 4.95 trillion. NRF’ s numbers come with the caveat that they do not include sales data from automobile dealers, gasoline stations and restaurants.
And it added that non-store and online sales year-over-year, which are included in the total figure, are expected to grow between 11% -to-13%, between $ 1.17 trillion-to- $ 1.19 trillion, a tally which continues to rise and has seen major traction even well before the pandemic over the last more than two years.
While this 2022 forecast falls short of the 14% annual retail sales growth rate seen in 2021, which NRF said marked the highest growth rate in more than 20 years, it noted that the 2022 forecast tops the 10-year, pre-pandemic growth rate of 3.7%.
NRF Chief Economist Jack Kleinhenz observed that the organization’ s forecast comes amid 40-year highs for inflation.
“ Most households have never experienced anything like this level of inflation, and it is expected to remain elevated well into 2023, ” said Kleinhenz. “ In addition to inflation, the forces impacting the economy include COVID-19 impacts, international tensions and policy variability.
And he also observed that while a roller coaster ride of incoming data is expected in the coming months, consumer fundamentals remain in place, in the form of healthy household finances, coupled with strong job and wage growth that he said should support solid growth for consumer spending for 2022.
What’ s more NRF said that NRF it anticipates strong job and wage growth and declining unemployment, while pegging full-year GDP growth to decrease to around 3.5% in 2022, due to the “ surge of inflation and tightening of monetary policy and less fiscal stimulus. ”
When taking into account the many challenges consumers and businesses face, this forecast is very strong, especially when taking into account the myriad of challenges shippers, carriers, logistics services providers, and, of course, consumers are still up against. Just because retail sales remain solid, by no means, eradicates the ongoing supply chain challenges, including port congestion, driver availability, labor shortages, the possibility of another Covid outbreak ( let’ s all hope we are past that!), and, now, the Russia-Ukraine conflict.
Again, uncertainty is everywhere, with the distinct exception of the frenzied pace of consumer spending, which the NRF’ s 2022 retail sales forecast makes very clear.
Strategic Real Estate. Applied Technology. Tailored Service. Creativity.… | general |
Q & A: Glenn Koepke, GM, Network Collaboration, FourKites | Logistics Management Group News Editor Jeff Berman recently spoke with Glenn Koepke, GM, Network Collaboration, for Chicago-based FourKites, a provider of real-time tracking and visibility solutions across transportation modes and digital platforms. Koepke provided Berman with an overview of the impact of the Russia-Ukraine conflict on North American supply chain and logistics operations, rates, capacity, and other topics. Their conversation follows below.
Glenn Koepke: There are three things we are seeing on that front.
One is pricing. We are going to see it in contracted rates but also in bunker surcharges. We may also see a byproduct of demurrage and detention as well, but that is typically related to other bottlenecks. We are going to see it in freight costs as well as the fuel impact, over the next couple of weeks, very significantly. That is very specific to the transactional market, with companies trying to hedge against the that. So, the companies that have larger volume that can commit to it will be buffered a little bit from this. But in the transactional market, where 3PLs and freight forwarders play quite a bit, they will also make higher margin off of it. I think we are going to see costs rise significantly in the North American market, specifically to importation so that is kind of number one.
Number two is just container capacity and getting containers on a vessel. I think we are going to see a rise in rolled containers and challenges with getting capacity at origin to be slotted into vessels and leave the port. As a byproduct of that, we are going to see worsened on-time shipping at origin, because as vessel operators try and figure out how do they take on the capacity, how they deploy new routes. These are very infrastructure -driven networks and they are not as agile as one would hope.
Third, we are going to see worse on-time delivery at U.S. and Canadian ports. The way companies are hedging against it now is that ports are asking companies to slow steam. It may not necessarily be reflected in the data as clearly, but the way it is going to show up is if you look at actual routing time from origin to the port of call destinations, we are going to see longer transit because ports are asking vessels to slow steam and slow things down…so it is either going to come up like that or it is going to come up also in the on-time delivery metrics at destination
In terms of sourcing, there is a question of if companies are going to near shore more now. My take is that it is not as impactful as what happened with the pandemic early on, in terms of the true global supply chain and trying to shut down and things like that, which crippled folks…and I think that educated people on where they could near shore. I think, certain industries, like oil and gas, wanted less dependency on Russia and Eastern bloc countries, but that is very niche to those industries at the moment.
Koepke: My take it is less so due to Ukraine and more so due to Covid. At the end of the day, if you are in the supply chain, you are looking at a few different things.
Koepke: One is what is my total landed costs? What is my supply chain infrastructure? And then you are looking at risks and trade policies that are in place. In the Trump administration, with duties and tariffs, that was wild. It was for certain commodities and that drove a lot more near sourcing, more so than what is going on in Russia and Ukraine right now. The net exporter to these countries is primarily oil and gas and heavy industrial. You can look at the automotive market and others and see there is a deep reliance on China and southeast Asia and Western Europe. So, I don’ t think this is going to drive a further discussion because of this one point, or event. I think it is a multitude of as we look into our buying habits, we have to minimize risk where we can, but, at the end of the day, all of these companies are generally profit-driven.
Koepke: If a consumer is willing to pay X% more to have locally sourced products, there are initial industries like apparel and others, where you can offer a premium price but when you look at mass amount of goods from a GDP standpoint, in terms of being a global economy and a global supply chain….if China gets into this, and they have stayed at somewhat of a distance and are trying to play “ Switzerland ” as they can, then that changes the entire world from a supply chain standpoint. Look at most anything in your house and it says “ made in China. ” If the U.S. and other countries were to put anything remotely close to the sanctions put on Russia to China for certain commodities and individuals, then we would be in a place where we would have to have a vertical supply chain within the U.S.
Koepke: When the U.S. first got intelligence that Russia may start a war, at that point, it was just heresay. The labor disagreement is always the biggest issue and the impact is that shippers are going to push capacity to the brink by buying product ahead of time from Asia to get into the U.S.
In parallel, they are going to see what they can re-route to go to the East Coast ports, but when you think of where most consumption is happening in the U.S. and why the ports of Los Angeles and Long Beach matter, there is a reason for it. Re-routing freight solves a small portion of the goods. I think we are going to see pricing go through the roof, and you are going to see capacity pushed to the brink again. You are going to see a pending recession that may happen. It is going to be an unexperienced couple of events we have not seen before, kind of like what we saw two years ago early on in Covid and last year. If you look at history, this is not going to go smoothly and there is going to be threats of strikes and delays and other ports are going to get freight that they can not handle and shippers are going to be in a tough spot. Meanwhile, the air cargo market is just going to go through the roof at that point in time but that is for specialized product. Most supply chains can not afford to airfreight a majority of their goods.
The economy is the biggest factor. if we start to see a recession and volumes go down, supply chains will ease capacity and bottlenecks will not be as disruptive. Where we stand right now, it is so volatile, and hard to predict what is going to happen next week
The major retailers are trying to compete and differentiate with Amazon long term. Wayfair has CastleGate logistics and Home Depot has its own logistics infrastructure, as examples. We are going to continue to see major retailers build out their freight forwarding arms, so they are operating as their own NVOCC ( non-vessel operating common carrier), and we are also going to see more companies make acquisitions in the final mile space, like how Innovel was acquired by Costco. Companies are trying to differentiate and keep customers where the majority of upper middle class to upper class Americans are willing to pay a premium
The days of people assuming Amazon is the lowest price for the most part is gone, as most people are willing to pay a premium for sake of ease. Other retailers and outlets are seeing that as companies convert to dark stores and final mile networks and personal networks. These are things that people are looking at. I do think we will see the top of the top companies continue to build out vertical delivery networks and use that as a way to retain customers as they go forward.
From a supplier standpoint, the whole ( FBA Fulfillment by Amazon) approach, for small-to-midsized companies, is a key differentiator and a great way to steal a business early on. Walmart is trying to get close to that and Wayfair is, too, in the furniture market, but they have a long way to go as well.
LM: While it remains unclear how long the Russia-Ukraine conflict will last, what are some of the key things shippers need to be focusing on, especially between now and this summer, when Peak Season kicks in.
Koepke: Many shippers are assessing their risk exposure from a Tier I and Tier II supplier standpoint. For example, as sanctions are put in place, maybe a shipper did not realize its Tier I supplier was actually buying spare parts from Russia, Ukraine or other countries impacted by this disruption. Supply chain risk exposure is number one, as it relates to where a shipper has exposure to critical products. Companies need to be doing it typically every three-to-five years, but more and more we are in the age where you just have to be continuously doing it.
Secondly, you need to be looking at demand forecasting and making some conservative predictions about where to buy ahead of time, whether it is raw materials or finished good production and for deployment. You have to be looking at a more aggressive production schedule to get ahead of things. But I think where companies are challenged right now is the question of whether we are on the brink of a recession or not? That is a tough exercise for companies that are trying to maximize profit yet make predictions that we can not answer.
The third thing is how do you change and enable different operational decisions, and today, I think, what is continually highlighted across companies is that they are living off of e-mail and spreadsheets. There are 7- and 8-figure ERP installations and all of this technology out there. But, for many companies, as you go further upstream in their supply chain—with production, raw materials, and risk management—there are very archaic tools companies are leveraging, and they are being forced to modernize their networks at a much faster pace than what they want because of these disruptions.
Strategic Real Estate. Applied Technology. Tailored Service. Creativity.… | general |
Once again, America is in denial about signs of a fresh Covid wave | In early 2020, with the major outbreak in the Lombardy region of Italy that rapidly and profoundly outstripped hospital resources and medical staffing, Americans expressed confidence it would not happen here. That it couldn’ t happen here. And then it did. Picture: AP
When it comes to Covid, the United States specialises in denialism. Deny the human-to-human transmission of the virus when China’ s first cases were publicised in late 2019. Deny that the virus is airborne. Deny the need for boosters across all adult age groups. There are many more examples, but now one stands out — learning from other countries.
In early 2020, with the major outbreak in the Lombardy region of Italy that rapidly and profoundly outstripped hospital resources and medical staffing, Americans expressed confidence it would not happen here. That it couldn’ t happen here. And then it did.
Fast forward two years of the pandemic: Britain and Europe have provided five unmistakable warnings to America that a new surge was occurring. Within weeks, each time, the United States experienced a new wave, some not as severe ( such as with the Alpha variant), some worse ( Delta and Omicron variants). From this Covid track record over two years, it is palpable: what happens in the UK and Europe doesn’ t stay in the UK and Europe.
In the past couple of weeks, the UK and several countries in Europe, including Germany, France and Switzerland, are experiencing a new wave. At least 12 countries, geographically extending from Finland to Greece, are experiencing new increases in cases, some quite marked, such as Austria exceeding its pandemic peak, and Finland with an 85% increase from the prior week. Many of these countries are also showing a rise in hospital admissions.
This is the sixth warning from the UK and Europe to the United States.
Indications within the United States support the idea that new wave is already getting started. Wastewater surveillance is relatively sparse in the United States, but 15% of the 410 sites where it was conducted between February 24 to March 10 showed a greater than 1000% increase compared with the prior 15-day period.
Also, the BA.2 variant is gaining steam in the United States and is now accounting for more than 30% of new cases.
The root cause for the new wave is hard to pin down. Certainly, the BA.2 variant is known to have increased transmission, at least about 30% more than its sister lineage, Omicron BA.1.
With the concomitant reduction of mitigation restrictions and waning immunity protection of vaccines, that transmission advantage will increase. This 'BA.2 triad ' of factors is thus hard to dissect, as they are clearly interdependent. Rather than focusing on what precisely is driving the new wave, the imperative is to drive some preventive action.
As with the first five warnings from the UK and Europe, the United States did not take heed. Instead of proactively gearing up with non-pharmaceutical interventions ( masks, quality of masks, distancing, air filtration, ventilation, aggressive testing, etc.), it just reacted to the surges when they were manifest.
Very low vaccination and booster rates
Now we are at a point with very low vaccination and booster rates, only 64% of the populations has had two shots, and 29% three shots. That puts the United States at 65th and 70th in the world ranking of countries, respectively.
Indeed, the people who need protection the most, besides those who are immunocompromised, are the 65-plus group. The US has a booster rate of 65% in this age group, whereas the UK and many European and Asian countries exceed a 90% booster rate for people 65 and over.
This is a critical issue, because there is a substantial dropdown of protection, from 90-95% with a third shot to 75-80% without a booster, versus Omicron hospitalisation and death. | general |
Sponsorship saga has to end for FAI as Boys in Green await backer | FAI chief executive Jonathan Hill has extensive commerical contacts but it has yet to result in a backer for the men's international team. Picture: Brian Lawless/PA Wire
When Ireland begin the international calendar year with a glamour friendly against Belgium next week, there’ ll be one notable absentee which is becoming increasingly difficult to comprehend.
The apparel which Stephen Kenny’ s players sport in training at Abbotstown from Monday will be devoid of a brand, two years on from mobile operator Three disconnecting their decade-long sponsorship.
How the jerseys and tracksuits remain blank on the national team of the country’ s most participated sport is moot, aggravated by the slew of excuses trotted out.
From the FAI’ s tarnished reputation to Covid-19 challenges and Brexit, the latest to get an airing is Russia’ s invasion of Ukraine. Unless the association soon ends its search, the need to man the barricades may be nigh.
With State funding to compensate for lost revenue during the pandemic ceasing, the FAI has to stand on its own two feet to financially function.
One will do for now and it starts with the fundamental of a marquee backer. That’ s not conjecture; just check out a caveat in the last set of accounts that showed debts of over €65m.
“ The association’ s underlying income is dependent upon variable revenue streams, including ticketing and commercial revenue, in order to achieve financial stability. Any reduction in revenue could result in an inability to make the investments needed in grassroots, high performance, clubs, leagues and international teams, as well as in support functions such as finance and human resources, ” sounded the warning.
Let’ s examine the figures for context. Three shelled out a basic €2.5m annually, before qualification bonuses, and the FAI is pitching to the market for a similar figure within a four-year package. By contrast, while much has been made of the 18,000 season tickets offloaded, the discounted nature and family bundle element brings the total revenue to around the same amount they’ ve missed out by failing to land a sponsor successor.
Three, and before them Opel and Eircom, primarily forked out a significant portion of their budget to attach themselves to a winning team. Corporate hospitality, along with meet-and-greets with players, are all well and good but the feelgood factor, especially deriving from major tournaments, is where brands capitalise on their investment.
In explaining the slowness of movement, the FAI preferred to cite historical damage rather than results on the pitch – well, up till last month anyway.
It’ s no secret that Jonathan Hill’ s stellar record in the commercial world of football was one of the decisive factors in his appointment as chief executive in November 2020, giving him the upperhand over corporate governance guru Sarah Keane. The big-ticket items from his commercial directorships at the English FA and Wembley were impressive; Nike’ s £300m deal, £36m from EON along with a £125m increase in domestic sponsorship over four years.
Despite triumphs in other aspects of his brief, transferring that midas touch to the Irish remains his biggest struggle.
Sky’ s arrival as the women’ s team partner in September, though welcome, banked a fraction of the men’ s equivalent and wasn’ t the first time the female squad attracted a standalone sponsor.
“ To find a new sponsor in a Covid scenario was always going to be a challenge, '' Hill said just over a year ago on the subject of filling Three’ s void.
`` That doesn’ t mean we're not in the market place. I believe we are the No 1 sport in the world and a World Cup qualification year reminds us of that. We are out there talking and it's our intention to find a partner. ''
Lots of talking has followed with little outcome. At the December meeting of the FAI’ s General Assembly, in response to an update request by delegate James Kelly, Hill stated that “ a number of ongoing conversations were ongoing ” and he was “ very hopeful ” of having a new flagship partner in place for the March double-header.
It appears to be more hope than expectation. Hill was the first to finally admit the performance of the senior side in Stephen Kenny’ s “ early stages ” were among the factors, a moment of frankness from the straight-talking Yorkshireman. He was stating the obvious, for its inconceivable that a company wouldn’ t have jumped aboard if Ireland were preparing for a World Cup playoff next week rather than dead-rubber friendlies.
Ireland haven’ t played in an empty stadium for a year and the macro conditions are favourable for a corporate pitching their wagon to a good news story that the diverse Irish squad is considered.
Exchequer returns from the private sector are booming and Ireland is a global hub for the pharma and tech sectors.
Indeed, several of the conglomerates are located close to the FAI’ s headquarters around the M50 belt. You’ d like to think Hill and his new commercial consultant Jonathan Neill are creating openings and getting to sell the story which he’ s convinced will stick. No longer can the FAI be imprisoned by its past, according to Roy Barrett. The Chairman isn’ t tolerating excuses concerning what his new broom inherited.
Sponsorship deals are there to be brokered, evidenced last week by Permanent TSB aligning with the Irish Olympic and Irish Paralympic teams for the Paris 2024 Games.
For a man partial to using a soundbite relating to direction of travel, we can only hope it starts heading up-Hill for the FAI’ s battered coffers.
Calendar season no panacea to climate challenge | general |
Cyteir Therapeutics Reports Fourth Quarter and Full Year 2021 Financial Results and Operational Highlights | - Continue to enroll in monotherapy and combination studies with CYT-0851 with potential for interim safety and efficacy data in second half 2022
- Progress achieved in key clinical milestones described in the 2021 IPO: Advanced CYT-0851 monotherapy to Phase 2 and initiated Phase 1 combination therapy study
- Projected cash runway into 2024 to support planned R & D and clinical studies
- Conference call and webcast scheduled for 4:30 p.m. ET on March 16, 2022
LEXINGTON, Mass. -- ( BUSINESS WIRE) -- Cyteir Therapeutics, Inc. ( “ Cyteir ”) ( Nasdaq: CYT), a company focused on the discovery and development of next-generation synthetically lethal therapies for cancer, today reported financial results for the fourth quarter and full year ended December 31, 2021 and provided an update on recent operational highlights.
“ In 2021, we made significant progress towards our goal of advancing our lead program CYT-0851 in the clinic with the completion of a dose escalation study and identification of the recommended Phase 2 dose. Our interim analysis demonstrated anti-tumor effects with disease control and responses in heavily pretreated and progressing lymphoma and solid tumor patients, with a safety profile consisting primarily of mild adverse events, ” said Markus Renschler, MD, President and Chief Executive Officer of Cyteir. “ We are now dosing patients in the Phase 2 monotherapy expansion cohorts and have begun Phase 1 combination therapy cohorts. We expect interim safety and efficacy data read-outs from these cohorts this year that may allow us to design one or more potentially registrational trials. We continue to invest in our pipeline and are advancing two new targets from our synthetic lethality DNA damage response platform toward the clinic. ”
Fourth Quarter and Full Year 2021 Accomplishments
Advanced CYT-0851 Clinical Program
Advanced DNA Damage Response ( DDR) Platform
Efficient execution of research and clinical strategy with cash runway into 2024
2022 Key Milestones Completed
2022 Expected Key Milestones Completed
Fourth Quarter and Full Year 2021 Financial Results
Cash and cash equivalents: Cash and cash equivalents as of December 31, 2021 were $ 189.7 million, which are expected to fund planned operations into 2024.
Research and development ( R & D) expenses: R & D expenses were $ 8.3 million for the fourth quarter of 2021 versus $ 3.9 million for the same period in 2020 and $ 31.0 million for the full year 2021 versus $ 16.8 million for full year 2020. The year-over-year increase in R & D spending in the comparative periods was due primarily to increased research activity, clinical trial expenses and headcount, including initiation of Phase 1 and Phase 2 studies for our product CYT-0851.
General and administrative ( G & A) expenses: G & A expenses were $ 3.6 million for the fourth quarter of 2021 compared to $ 1.5 million for the same period in 2020 and $ 11.3 million for the full year 2021 compared to $ 4.2 million for full year 2020. The year-over-year increase in G & A expenses in the comparative periods was primarily due to employee-related costs, as well as other administrative expenses associated with company growth and operating as a public company.
Net loss: Net loss was $ 11.8 million, or $ 0.34 per share, in the fourth quarter of 2021 compared to $ 5.4 million, or $ 2.92 per share, for the same period in 2020. For the full year 2021, net loss was $ 42.1 million, or $ 2.16 per share compared to $ 20.8 million, or $ 13.60 per share for full year 2020.
Fourth Quarter and Full year 2021 Conference Call and Webcast Information
Cyteir will host a conference call to discuss the fourth quarter and full year of 2021 financial and operational results on Wednesday, March 16, 2022, at 4:30 p.m. ET. The conference call will be available by webcast on the Investor Relations page at www.cyteir.com. An audio replay of the call will be available on the website after 9:00 p.m. ET the same day.
About Cyteir Therapeutics, Inc.
Cyteir is a clinical-stage oncology company that is focused on the discovery and development of next-generation synthetically lethal therapies to treat cancer. The company is using its expertise in DNA damage response biology to advance a pipeline of novel drug candidates that selectively target key cancer vulnerabilities. Cyteir’ s wholly owned lead compound, CYT-0851, is a selective, oral investigational drug that was designed to inhibit DNA repair.
Forward-Looking Statements
This press release contains “ forward-looking statements ” regarding Cyteir’ s expected developments related to clinical trials, timing and results of our preclinical and clinical studies, our plans to develop patient selection biomarkers, 2022 expected key milestones and our expected cash runway. Forward-looking statements include statements identified by words such as “ could, ” “ may, ” “ might, ” “ will, ” “ likely, ” “ anticipates, ” “ intends, ” “ plans, ” “ seeks, ” “ believes, ” “ estimates, ” “ expects, ” “ continues, ” “ projects ” and similar references to future periods. Forward-looking statements are based on our current expectations and assumptions regarding capital market conditions, our business, the economy and other future conditions. Because forward-looking statements relate to the future, by their nature, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict. As a result, actual results may differ materially from those contemplated by the forward-looking statements. Important factors that could cause actual results to differ materially from those in the forward-looking statements include: our limited operating history and that we have no products approved for commercial sale, which may make it difficult for you to evaluate our current business and predict our future success and viability; that we have incurred significant losses since inception and expect to incur losses for the foreseeable future and may never achieve or maintain profitability; our need substantial additional funding; that we have never successfully completed any clinical trials, and we may be unable to do so for any drug candidates we develop; that our clinical trials may fail to demonstrate adequately the safety and efficacy of any of our drug candidates, which would delay or prevent further clinical development of those candidates, or prevent marketing approval from FDA or similar regulatory authorities; that we are developing CYT-0851, and potentially future drug candidates, for use in combination with other therapies, which exposes us to additional risks; if we are unable to successfully develop and commercialize companion diagnostic tests for our drug candidates, or experience significant delays in doing so, we may not realize the full commercial potential of our drug candidates; synthetic lethality represents an emerging class of precision medicine targets, and negative perceptions of the efficacy, safety or tolerability of this class of targets, including any that we develop, could adversely affect our ability to conduct our business, advance our drug candidates or obtain regulatory approvals; if we are unable to adequately protect and enforce our intellectual property or obtain and maintain patent protection for our technology and products or if the scope of the patent protection obtained is not sufficiently broad, our competitors or other third parties could develop and commercialize technology and products similar or identical to ours, and our ability to successfully develop and commercialize our technology and products may be impaired; that the continuing outbreak of COVID-19 ( including any resurgences, including due to variants, thereof) in the United States and other countries and shortages of qualified healthcare personnel may adversely affect our business and the market price of our common stock; and other factors set forth under the heading “ Risk Factors ” in Cyteir’ s final prospectus dated June 17, 2021 and our filings that we make from time to time with the Securities and Exchange Commission ( the “ SEC ”). Any forward-looking statement made in this press release speaks only as of the date on which it is made. The company does not undertake any obligation to update any such statement or to publicly announce the results of any revisions to any such statements to reflect future events or developments, except as required by law.
For further information, please reference the company’ s reports and documents filed with the SEC. You may get these documents by visiting EDGAR on the SEC website at www.sec.gov.
( in thousands, except share and per share amounts)
( unaudited)
Three Months Ended December 31,
Years Ended December 31,
2021
2020
2021
2020
$
8,255
$
3,917
$
30,959
$
16,765
3,607
1,463
11,300
4,178
11,862
5,380
42,259
20,943
( 11,862
)
( 5,380
)
( 42,259
)
( 20,943
)
47
20
133
120
47
20
133
120
$
( 11,815
)
$
( 5,360
)
$
( 42,126
)
$
( 20,823
)
$
( 0.34
)
$
( 2.92
)
$
( 2.16
)
$
( 13.60
)
35,136,168
1,837,268
19,499,292
1,530,924
Research and development expenses for the fourth quarter and full year-ended December 31, 2021 include stock-based compensation expense of $ 0.4 million and $ 1.2 million, respectively, compared to $ 0.1 million and $ 0.2 million, respectively, in the corresponding periods of 2020. General and administrative expenses for the fourth quarter and full year-ended December 31, 2021 include stock-based compensation expense of $ 0.8 million and $ 2.3 million, respectively, compared to $ 0.1 million and $ 0.3 million, respectively, in the corresponding periods of 2020.
( in thousands, except share and per share amounts)
( unaudited)
December 31,
2021
2020
$
189,723
$
10,938
3,354
1,193
$
193,077
$
12,131
2,055
1,287
256
317
$
195,388
$
13,735
$
1,785
$
1,689
5,726
1,448
$
7,511
$
3,137
384
452
201
766
$
8,096
$
4,355
-
5,696
-
51,715
-
-
-
-
35
2
279,310
1,894
( 92,053
)
( 49,927
)
187,292
( 48,031
)
$
195,388
$
13,735 | general |
Asian Markets Bounce As Hong Kong Tech Sees Bargain-buying | Asian markets saw a much-needed bounce Wednesday as Hong Kong's tech giants led a rally in the city after their recent rout, while oil prices rose back above $ 100 but remain pressured by concerns over demand from China.
However, while the gains are keenly welcomed, further volatility is expected as Russia presses ahead with its war in Ukraine and the Federal Reserve starts its campaign of interest rate hikes to fight inflation.
Trading screens were swathed in red of late as investors fretted over the war in eastern Europe, the spike in prices and a Covid outbreak across China that has led to the lockdown of several cities including the key tech hub of Shenzhen.
Hong Kong was the worst-hit, with around 10 percent scythed off the Hang Seng Index in three days as tech titans such as Alibaba, JD.com and Tencent were tossed out by panicked dealers.
The sector has been battered owing to concerns about regulatory crackdowns by Beijing as well as US authorities, while there were also growing worries about possible US sanctions if China were to help Russia in its war with Ukraine.
News that the southern Chinese tech hub of Shenzhen had been put into lockdown to fight a Covid outbreak compounded the crisis.
However, Hong Kong clawed back some of its losses Wednesday, rising more than three percent at one point, thanks to a more than six percent advance in the Hang Seng Tech Index.
JD.com rocketed 14 percent while Alibaba and Tencent rose more than six percent apiece. NetEase, XD Inc and Meituan were also enjoying outsized gains.
And the rest of Asia joined in, tracking a dip-buying rally on Wall Street.
Tokyo and Singapore piled on more than one percent, while Shanghai, Sydney, Seoul, Wellington, Taipei, and Jakarta were also up.
Sentiment has been given some support by a sharp drop in oil prices, just a week after they hit 14-year highs and ramped up fears over already elevated inflation.
Both main contracts fell below $ 100 Tuesday as lockdowns in several big Chinese cities led to fears about the economy and demand in the world's biggest importer of the commodity.
Hopes for the Iran nuclear deal -- which could see Tehran restart global exports of oil -- have helped weigh on prices, as have signs that Russia-Ukraine ceasefire talks are slowly progressing.
However, crude enjoyed some fresh buying sentiment Wednesday, with Brent back into triple figures with expectations that sanctions on Russia will mean supplies remain tight even if the war is brought to an end soon.
The spike in crude as well as other commodities including wheat and metals has caused a headache for central banks as they try to move away from pandemic-era monetary policy and try to rein in inflation.
And the Federal Reserve's meeting, which concludes later Wednesday, is in focus as it prepares for what is expected to be a series of hikes this year.
While the increase has been accounted for by investors, they will be keeping a close watch on what bank boss Jerome Powell says afterwards, in light of the Ukraine war and a possible slowdown in economic growth.
Meanwhile, data shows US consumer prices are rising at their fastest pace in 40 years.
`` The confluence of events leading in to this meeting puts policy makers in a very unenviable position, '' Matt Rowe, at Nomura Securities International, told Bloomberg Television.
`` It's being publicly debated whether if you create a recession to push the number down to two percent, is that actually a policy error? '' he added, referring to inflation.
Tokyo - Nikkei 225: UP 1.7 percent at 25,784.71 ( break)
Hong Kong - Hang Seng Index: UP 2.4 percent at 18,857.74
Shanghai - Composite: UP 0.1 percent at 3,066.45
West Texas Intermediate: UP 1.1 percent at $ 97.52 per barrel
Brent North Sea crude: UP 1.5 percent at $ 101.52 per barrel
Euro/dollar: UP at $ 1.0973 from $ 1.0951 late Tuesday
Pound/dollar: UP at $ 1.3054 from $ 1.3036
Euro/pound: DOWN at 84.06 pence from 83.92 pence
Dollar/yen: UP at 118.25 yen from 118.33 yen
New York - DOW: UP 1.8 percent at 33,544.34 ( close) | business |
Djokovic Free To Play French Open 'As Things Stand ', Say Organisers | Unvaccinated players, including Novak Djokovic, will be free to play at this year's French Open `` as it stands '', the French Tennis Federation ( FFT) said on Wednesday.
Djokovic, who will reclaim his world number one ranking next week, was forced to miss the Australian Open when he was deported from the country following a legal battle over his lack of Covid vaccinations.
There was doubt over his participation at Roland Garros, but with France's vaccine pass and other Covid rules dropped this week, tournament director Amelie Mauresmo says he is free to take part.
`` As things stand, nothing stands in the way of Djokovic taking part in the French Open, '' she told a press conference. `` Our goal is to have the best possible entry list. ''
Djokovic has been clear in his refusal to have a Covid vaccine and the 20-time Grand Slam champion was also forced to sit out the ongoing Indian Wells tournament in the United States.
Roland Garros organisers were also keen to stress that the situation could change.
`` We have learned to be extremely careful, '' said FFT director general Amelie Oudea-Castera.
`` We see that from month to month things can change. In a difficult scenario, there will always be a way to reintroduce the health bubbles. ''
Djokovic missed out on a tilt at a record-breaking 21st men's Grand Slam title in Australia, where his rival Rafael Nadal took the trophy, and the record.
The FFT also said Tuesday that Russian and Belarusian players would be able to compete, but under a neutral flag. | business |
Fed Set To Raise Interest Rates To Rein In Inflation | US central bankers on Wednesday are poised to take the first step to raise borrowing costs in a bid to cap rising inflation before it surges out of control.
The Federal Reserve will have to walk a tightrope to ensure its efforts don't derail the recovery from the Covid-19 pandemic as Russia's invasion of Ukraine introduces new uncertainty in an economy battered by supply chain snarls and labor shortages.
`` There is no good answer to that in any economics textbook, '' David Wilcox, a former senior Fed advisor, told AFP, stressing that communication from the central bank about its willingness to act will be key in pulling off its balancing act.
The central bank's Federal Open Market Committee opened its second day of deliberations early Wednesday and is due to announce its rate decision at 1800 GMT.
Fed Chair Jerome Powell has said he favors increasing the benchmark interest rate by 0.25 percentage points from zero, where it has been since March 2020.
It would be the first in a series of hikes, which would pull back on the stimulus rushed into place at the start of the Covid-19 pandemic.
The Fed chief has expressed confidence that inflation will retreat in the coming months as supply chain issues and shortages are resolved in the world's largest economy.
But China's latest lockdowns of several cities, affecting tens of millions of people and closing off a key supplier to American tech giant Apple, shows the pandemic and its disruptions are not over.
Policymakers are better equipped to handle inflation that is too high rather than too low, as was the case in the decade following the 2008 global financial crisis, during which inflation and employment were slow to recover.
However, with the annual consumer price index growing 7.9 percent in February, its fastest pace in four decades, the central bank faces intense criticism that it missed the inflation danger, and has moved too slowly in response to rising prices for cars, housing and food.
And the war in Ukraine together with Western sanctions on Russia have sent oil prices surging, although they retreated Tuesday closing below $ 100 a barrel for the first time in three weeks.
`` The Federal Reserve's delays in raising interest rates and its continued misreading of inflation, monetary and fiscal policies are now complicated by the negative supply shock imposed by Russia's invasion of Ukraine, '' said Mickey Levy of Berenberg Capital Markets.
`` Even without the surge in oil and commodity prices, the Fed is wrong on every count, '' Levy wrote in a column in The Wall Street Journal, saying the central bank `` must begin to raise rates. ''
But Wilcox, now with the Peterson Institute for International Economics and Bloomberg Economics, defended the Fed's performance, saying officials have adjusted to changing circumstances.
`` I think the allegation that the Fed is behind the curve is considerably overdone, '' he said. `` They have been caught by surprise, as the vast majority of prognosticators were, '' but `` they 've had the guts and the courage '' to change their mind publicly.
Wall Street was in a cheerful mood ahead of the decision, with all three major indices up decisively in early trading.
Briefing.com analyst Patrick J. O'Hare said the sentiment was partly fueled by hopefulness -- however premature -- around Russia-Ukraine peace talks, and the expectation of further gains once the Fed makes its announcement.
`` The supposition with respect to today's policy decision is that it could ultimately translate into a buy-the-fact event since the market has already sold the rumor, '' O'Hare said.
Economists project six or seven rate increases this year, which would still leave the policy rate below two percent, assuming central bankers raise it in quarter-point steps.
However, Powell and other policymakers have stressed that they will do whatever is needed to tamp down inflation, including more aggressive hikes. | business |
EU, India, South Africa, US Reach Vaccine TRIPS Waiver Deal | The Office of the U.S. Trade Representative has confirmed that there has been a compromise reached between the four major players in discussions to waive intellectual property rights for COVID-19 vaccines.USTR spokesperson Adam Hodge on Tuesday night said South Africa, India, the European Union and the U.S. have agreed in principle to waive certain provisions of the World Trade Organization's Agreement on Trade-Related Aspects of Intellectual Property Rights, or TRIPS, but formal terms of the deal still need to be ironed out and approved by the WTO's other 160 members. `` The difficult and protracted process has resulted in a compromise outcome that offers... | general |
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Port of Los Angeles container volumes could'soften ' this spring | The nation’ s largest container port set a February cargo record and processed a nearly 19% increase in empties YoY, Executive Director Gene Seroka said in a briefing.
Container volumes at the Port of Los Angeles are expected to soften this spring compared to last year, and the port will use any lull from COVID-19 lockdowns in China to keep tackling cargo backlogs, Executive Director Gene Seroka said in a briefing Wednesday.
Retailers plan to replenish low inventories, which should help imports remain at `` solid '' levels, even if they dip from the 970,000 TEUs on average between March and May of 2021. And the ripple effects of factory shutdowns in China might even benefit port operations, Seroka said.
`` In the event we have a lull due to shutdowns at ports, terminals, factories, other businesses that convey the cargo, it’ s going to give us a chance to catch up even more so than we have done right now, '' he said.
The remarks, delivered from New York, came during the Port of Los Angeles monthly briefing on cargo volumes and other performance indicators. The nation’ s largest container port handled 857,764 TEUs, a February cargo record, and processed 338,251 TEUs of empties — an 18.6% increase YoY — last month amid record levels of empty repositioning back to Asia.
The port has also seen the proportion of imports to exports continue to rise. Imports increased 2.7% to 424,073 TEUs YoY, while exports fell 5.7% YoY to 95,441 TEUs, the 36th decrease in the past 40 months.
Seroka pushed back on the phrase `` port congestion '' during the briefing and continued to cite the port's roughly 55% of unused truck gate appointments as an issue keeping the port from unlocking its full potential.
`` Is it chassis dislocation? '' the executive director mused. `` Is it the inability to service at the terminal because you 've got to dig through so many containers? Long truck lines? Is it operational improvements that must be made? Are there other things that we're not seeing that have to be brought to the forefront? ''
`` Probably those and many more, '' Seroka said.
State and national governments are accelerating efforts to help the ports and other supply chain stakeholders ease congestion.
Dee Dee Meyers, director of the California Governor’ s Office of Budget and Economic Development, joined the briefing to tout Gov. Gavin Newsom’ s plan to invest a record $ 2.3 billion in California ports in the upcoming budget. The money includes a planned $ 1.2 billion dollars for port infrastructure and goods movement, including rail, roadway, bridge and zero-emission modernization projects.
`` We're already talking to stakeholders about what their priorities will be, assuming we get these funds, and we will work very hard to make that happen, '' Meyers said.
On the national level, the Port of Los Angeles, the Port of Long Beach and the Georgia Ports Authority will pilot a data-sharing portal announced Tuesday by the White House.
The Freight Logistics Optimization Works program, which includes 15 companies at first, will build on lessons learned from the Port Optimizer platform, Seroka said.
`` The Port Optimizer in Los Angeles will play whatever the role is outlined by the federal and state governments, along with our private sector partners, '' Seroka said. `` There's some replications of best practices that can get this pilot up and running, and cut the learning curve down very swiftly. ''
There's another looming worry on local, state and national leaders ' minds: port contracts.
The International Longshore and Warehouse Union bargaining with management in May is expected to extend beyond the June 30 expiration date, Seroka said. COVID-19 has hit the dockworkers union hard: More than 40 have died of the virus during the pandemic.
During Seroka's visit to Washington, D.C. Tuesday for the announcement of the data-sharing portal, he said, leaders at the highest levels of the government expressed a focus on the upcoming union negotiations and their implications for supply chains.
`` The eyes of the nation are on this, '' he said.
Topics covered: logistics, freight, operations, procurement, regulation, technology, risk/resilience and more.
Robotics, conveyor belts and software become staples of the warehouse as e-commerce grows.
Many planes capable of transporting heavy goods are part of fleets from Ukraine and Russia.
Topics covered: logistics, freight, operations, procurement, regulation, technology, risk/resilience and more.
Topics covered: logistics, freight, operations, procurement, regulation, technology, risk/resilience and more.
Robotics, conveyor belts and software become staples of the warehouse as e-commerce grows.
Many planes capable of transporting heavy goods are part of fleets from Ukraine and Russia.
Topics covered: logistics, freight, operations, procurement, regulation, technology, risk/resilience and more. | general |
Amazon is slowing down its fulfillment center spend. What's next? | Heightened demand put Amazon's distribution buildout into overdrive. To speed up delivery and limit costs, it will have to invest more.
Amazon spent the past two years absorbing real estate space across the United States. It built new fulfillment centers to meet ballooning demand. Now, its breakneck pace may soon be slowing as it turns its attention to other nodes of its supply chain — including heavier investments in transportation.
A massive real estate footprint is a critical aspect of Amazon's strategy. Operating its own fulfillment centers, sortation centers and delivery stations provides greater control over the supply chain, allowing the company to deliver on the shipping speeds it promises Prime members.
`` Shipping speed is the growth driver in e-commerce, '' said Shipium co-founder and CEO Jason Murray, former vice president of supply chain and retail services at Amazon. `` Prime submitted that as the number one fact. You can do whatever you want with marketing, checkout, one-click ( ordering), whatever it is — speed is what drives everything. ''
Amazon's real estate footprint is a case in point. The e-commerce giant nearly doubled its operations capacity in the past two years to keep up with demand, CFO Brian Olsavsky said on an earnings call in February. Fulfillment center growth has been a large part of this equation — Amazon grew its number of U.S. fulfillment centers by 30% in 2021, according to data from supply chain consulting firm MWPVL International as of Feb. 16.
But investments alone have not been enough for Amazon to reach its desired shipping speeds. One-day delivery levels for Prime services are not yet back to where they were pre-pandemic. So now, Amazon is looking closer at other operational investments to boost its shipping capabilities.
`` We see [ fulfillment center spend ] moderating, '' Olsavsky said, adding future growth will probably match other sides of the business.
Experts say the development was likely after the initial e-commerce boom fueled by the COVID-19 pandemic cooled off.
A flood of online orders caused retailers to adjust – or accelerate – their logistics plans. Foot traffic at brick and mortar stores declined as the pandemic took hold and many consumers opted to shop more often online. In June, Olsavsky said Amazon had been playing catchup to match supply with demand – fulfillment costs as a percentage of net sales climbed from 15.2% in 2020 to 16% in 2021, according to Amazon's 10-K.
Adding more facilities in more markets allows Amazon to grow its capacity while positioning inventory closer to customers for faster and less-expensive delivery. Other companies in the e-commerce space are doing the same.
`` The e-commerce share of leasing has really steadied since last year, but it's still higher than pre-pandemic levels, '' said Heather Belfor, director and head of U.S. research at Prologis, which has Amazon as its top customer. `` Amazon is still obviously a major player within the e-commerce space, but it's very diverse because users need more logistics space across the supply chain. ''
Walmart, for example, is opening its own fulfillment centers and investing in an automated supply chain as it pursues more subscriptions for Prime competitor Walmart+. And Target has four more distribution facilities in development `` with plans for several more to follow, '' Executive Vice President and COO John Mulligan said on the company's Q4 earnings call. The retail titans also have the ability to use their brick and mortar locations scattered throughout the U.S. for omnichannel fulfillment, a critical development as companies try to limit their delivery costs for online orders.
Meanwhile, Amazon's slowdown in its fulfillment center buildout appears to already be occurring. Per MWPVL data, the fulfillment center growth rate is currently set to be 22% in 2022. Marc Wulfraat, president and founder of the firm, noted that figure is affected by many existing projects being pushed into this year due to lengthy supply lead times.
Still, among e-commerce platforms, Amazon is unmatched, said Jean-Paul Rodrigue, a professor of Global Studies and Geography at Hofstra University who researches freight distribution. Its domestic distribution infrastructure also towered over Walmart and Target's combined footprint by roughly 173 million square feet, per MWPVL.
`` You have that ( omnichannel) competition, but it's essentially Walmart offering simply an expansion of its services — that's not the same thing, '' Rodrigue said.
Although Amazon is easing its fulfillment center growth as competitors try to bolster their own distribution capabilities, other areas of its operations are still receiving plenty of attention. Olsavsky hinted at `` additional levels of investment '' in transportation capacity coming in 2022.
With more people and vehicles moving goods, Amazon can deliver to rural areas of the U.S. without calling on the services of UPS and the Postal Service, Wulfraat said.
`` We think that's what their goal is, that they want total control over their destiny when it comes to delivery, '' Wulfraat said. `` We think that ultimately they do want to eliminate UPS and USPS as partners. There's certainly a lot of clues that lead us to believe that. ''
Greater transportation control would help shield Amazon against rising costs. Amazon reported higher third-party carrier costs in Q4 — an incentive to invest in owned capacity.
Observers say Amazon could have additional long-term pursuits. The company could build more delivery stations, in which customer orders are prepared for last-mile services. It could explore investments to insulate itself further from global supply chain disruptions. Or, it could find ways to penetrate further into a difficult grocery market.
`` Everyone buys food, everyone buys a lot of it, '' Murray said. `` They're going to have to find a way to continue to be relevant in that space. I think Whole Foods has been okay, but it hasn't moved the needle. ''
One thing company observers agreed on is that Amazon isn't satiated with its current fulfillment network, and `` moderating '' is a relative term for a company that has invested in and grown its fulfillment network at an unmatched rate to set itself apart from competitors. Olsavsky even noted on the Q4 earnings call that fulfillment center spending could tick up once again in the future.
`` I think they're slowing down or decelerating, '' Wulfraat said. But they haven't stopped. `` That's certainly not the case. ''
Editor's note: This story was first published in our Logistics Weekly newsletter. Sign up here.
Topics covered: logistics, freight, operations, procurement, regulation, technology, risk/resilience and more.
Robotics, conveyor belts and software become staples of the warehouse as e-commerce grows.
Many planes capable of transporting heavy goods are part of fleets from Ukraine and Russia.
Topics covered: logistics, freight, operations, procurement, regulation, technology, risk/resilience and more.
Topics covered: logistics, freight, operations, procurement, regulation, technology, risk/resilience and more.
Robotics, conveyor belts and software become staples of the warehouse as e-commerce grows.
Many planes capable of transporting heavy goods are part of fleets from Ukraine and Russia.
Topics covered: logistics, freight, operations, procurement, regulation, technology, risk/resilience and more. | general |
Balwani Trial Openings Delayed Due To COVID-19 Exposure | A California federal judge delayed opening statements scheduled for Wednesday morning in the criminal fraud trial of former Theranos executive Ramesh `` Sunny '' Balwani after learning someone in the courtroom was exposed to a person infected with COVID-19.Roughly 20 minutes after opening statements were scheduled to begin in the highly anticipated trial, U.S. District Judge Edward Davila told jurors and a packed courtroom full of press and attorneys that a person who attended jury selection Tuesday notified the court that the individual had been in contact with someone who tested positive for COVID-19.Former Theranos executive Ramesh `` Sunny '' Balwani, right, stands... | general |
2nd Circ. Says Gov't Can Deny COVID Loans To The Bankrupt | The Second Circuit on Thursday overturned a bankruptcy court's finding that the U.S. Small Business Administration could not deny a Paycheck Protection Act loan to a bankrupt Vermont hospital, saying a loan that may not have to be repaid is still a loan.In its opinion, the panel found that the Vermont bankruptcy judge had erred in finding that PPP payments were grants protected by rules forbidding bankruptcy discrimination, saying the fact that the government could waive repayment doesn't turn a loan into a grant. `` A forgiveness option, favorable as it is, can not alter the structure of what a loan forgiveness... | general |
Virus Whistleblower Suit Short On Specifics, NJ Officials Say | New Jersey's acting attorney general and Gov. Phil Murphy's top aide have each called on a state court to toss a former health official's whistleblower lawsuit over alleged coronavirus testing favoritism, arguing that the claims don't spell out their supposed wrongdoing.In dismissal briefs filed Tuesday, acting New Jersey Attorney General Matt Platkin and Murphy's Chief of Staff George Helmy said the latest version of the lawsuit by onetime Assistant Department of Health Commissioner Christopher Neuwirth can't stick. Neuwirth claims he was fired after complaining that he was asked as a `` favor '' to use scarce COVID-19 testing supplies for Helmy's relatives.... | general |
Liberty Unit Doesn't Owe Coverage In Eateries ' Virus Suit | A group of Mississippi restaurant operators lost their bid for coverage of their pandemic-related losses from a Liberty Mutual unit when a federal judge decided they didn't allege the presence of the coronavirus at their properties.U.S. District Judge Debra M. Brown on Tuesday said University Management Inc. and three other restaurant operators couldn't show in their suit against State Auto Property & Casualty Insurance Co. that government orders meant to prevent the spread of COVID-19 were put in place to address contamination at their eateries. `` The express language of the executive orders directly contradicts UMI's position because it addresses the... | general |
Oil futures: Prices rebound as Russian invasion continues, Brent around $ 102.50/b | Quantum Commodity Intelligence – Crude oil futures in European trading hours Wednesday were trending higher following five sessions of straight losses as Russia's invasion of Ukraine continues with no immediate sign of a ceasefire, although China's rising Covid cases and progress on Iranian nuclear talks pared further gains.
Front-month May ICE Brent futures were trading at $ 102.54/barrel ( 0847 GMT), compared to Tuesday's settle of $ 99.91/b.
At the same time, April NYMEX WTI was trading $ 98.30/b, versus Tuesday's settle of $ 96.44/b.
`` Oil prices stabilised after Russian President, Vladimir Putin, cast doubt on the success of negotiations with Ukraine. Putin said that Ukraine was not showing a serious attitude toward finding a mutually acceptable solution, '' said ANZ commodity strategist Daniel Hynes.
Ukrainian Presiden Zelensky said on Wednesday peace talks with Russia were sounding `` more realistic '' but that more time was needed for any deal to be in the interests of Ukraine.
US President Joe Biden will travel to Brussels next week to meet with NATO allies about bolstering support for Ukraine as it fights to fend off Russia's unprovoked attack.
The `` extraordinary summit '' on 24 March will bring together leaders to discuss `` further strengthening NATO's deterrence & defence, '' NATO Secretary-General Jens Stoltenberg said.
Russian exports and potentially production remain under threat, although steep discounts have encouraged some buyers to continue purchasing spot Russian crude.
`` Given the weakness that we have seen in the market over the last week, it is clear that there is little risk premium priced into the market, which leaves it vulnerable to upward spikes if there is a deterioration in the Russia-Ukraine war, '' said Warren Patterson, head of ING's commodity research, noting Brent has fallen by around 28% since trading to an intraday high of US $ 139.13/bbl back on 7 March.
Meanwhile, China has reported Covid cases in 21 provinces, leaving around 37 million people in lockdown as of Tuesday.
Russia's Foreign Minister Sergey Lavrov said Tuesday that Moscow had received guarantees from the US on its ability to trade with Tehran as part of ongoing talks to salvage the Iran nuclear deal, which analysts see as a potential path to resuming the 2015 nuclear accord.
OPEC said Tuesday that it still expected oil demand to rise by 4.2 million bpd in 2022, a 20% slowdown in growth year-on-year, but warned that a slowdown in economic growth due to higher inflation and the war in Eastern Europe meant there was some downside risk. | general |
Here's what the weather will be like on St Patrick's Day and for the long weekend | Pupils from Gaelscoil An Teaghlaigh Naofa, Ballyphehane, Cork City, hold a St Patrick's Day parade in Tory Top Park. Picture: Larry Cummins.
After being hit by the Covid-19 pandemic in recent years, St Patrick’ s Day celebrations will return this weekend.
Two bank holidays lead the country into the weekend, but will there be rain on the parades?
Here's what the weather will look like over the long weekend.
St Patrick's Day, March 17
The feast day of our patron saint may see some showers but it should be a largely dry day.
Met Éireann is predicting that St Patrick's Day will see `` a few brighter spells '' but there will be a good deal of cloud `` bringing some showers eastwards across the country ''.
In the afternoon, with parades happening across the country, `` mainly dry weather '' will follow from the west with `` sunny spells developing ''.
Thursday night will be dry and there will be clear spells and frost in places.
It will, however, be cold with temperatures falling to lows of -2C.
Friday, March 18
Friday is another bank holiday, dedicated to healthcare workers and those who have lost their lives during the pandemic.
People will be able to mark the day with decent weather, with Met Éireann predicting it will be a warm and dry day `` with good sunny spells ''.
It will also be `` noticeably milder '' with temperatures reaching highs of 10C to 15C. | general |
Oil futures: Brent prices below $ 98/b on US stock build, Iran nuclear talks | Crude oil futures Wednesday were off from the day's highs as markets slid on China's rising Covid cases and progress on the Iranian nuclear talks, having initially posted firm gains as Russia's invasion of Ukraine continued with no sign of an immediate ceasefire.
Prices also came under pressure after the Energy Information Administration reported a 4.3 million/b rise in US crude stocks last week, compared to expectations of a small draw, while Libya effectively broke ranks in calling for OPEC to hike output.
Front-month May ICE Brent futures were trading at $ 97.79/barrel ( 2040 GMT), compared to Tuesday's settle of $ 99.91/b, and around $ 6/b off from Wednesday's high of $ 103.70/b.
At the same time, April NYMEX WTI was trading $ 95.09/b, versus Tuesday's settle of $ 96.44/b, as futures contracts continued to experience wild price swings.
Russia's Foreign Minister Sergey Lavrov said that Moscow had received guarantees from the US on its ability to trade with Tehran as part of ongoing talks to salvage the Iran nuclear deal, which analysts see as a potential path to resuming the 2015 nuclear accord.
`` This appears to remove one major obstacle to the revival of the 2015 nuclear agreement, paving the way for US sanctions against Iran to be lifted and thereby allowing Iranian oil exports to resume, '' said Carsten Fritsch of Commerzbank.
Prices briefly recovered from lows after the IEA warned lost Russian oil production could reach 3 million bpd by April as western buyers shun Russian molecules, leaving the global energy market set for a “ supply shock ”, the IEA said in its monthly report Wednesday.
Ukrainian Presiden Zelensky said on Wednesday peace talks with Russia were sounding `` more realistic '' but that more time was needed for any deal to be in the interests of Ukraine.
US President Joe Biden will travel to Brussels next week to meet with NATO allies and discuss bolstering support for Ukraine as it fights to fend off Russia's attack.
The `` extraordinary summit '' on 24 March will bring together leaders to discuss `` further strengthening NATO's deterrence & defence, '' NATO Secretary-General Jens Stoltenberg said.
Russian exports and potentially production remain under threat, although steep discounts have encouraged some buyers to continue purchasing spot Russian crude.
`` Given the weakness that we have seen in the market over the last week, it is clear that there is little risk premium priced into the market, which leaves it vulnerable to upward spikes if there is a deterioration in the Russia-Ukraine war, '' said Warren Patterson, head of ING's commodity research, noting Brent has fallen by around 28% since trading to an intraday high of US $ 139.13/b back on 7 March.
Meanwhile, China has reported Covid cases in 21 provinces, leaving over 35 million people in lockdown as of Wednesday.
OPEC said Tuesday that it still expected oil demand to rise by 4.2 million bpd in 2022, a 20% fall in growth year-on-year, but warned that a slowdown in economic growth due to higher inflation and the war in Eastern Europe meant there was some downside risk. | general |
Costco grows its LTL arm to fulfill 85% of big-and-bulky home deliveries | Costco's acquisition of a middle- and final-mile carrier as the COVID-19 pandemic took hold has allowed the retailer to take more control over its delivery process during an e-commerce-driven LTL boom.
`` We certainly didn't know that we would sell more big and bulky items. What we're finding is because people are at home, notwithstanding some of the economic things of layoffs and furloughs, people are buying things for the house, '' Galanti said of the acquisition in May 2020.
This includes big and bulky items offered for in-home delivery through Costco Logistics such as refrigerators, washers and dryers, ovens, grills and mattresses. Big and bulky items made up over a third of Costco's e-commerce sales, Galanti said in December.
The share of large e-commerce shipments delivered by Costco Logistics has grown since the acquisition. The 85% rate Galanti disclosed is an improvement from Q1, in which Costco Logistics deliveries represented 70% of the company's U.S. e-commerce bulky shipments.
When acquired by Costco, Innovel had network coverage to nearly 90% of the U.S. and Puerto Rico and more than 1,500 employees. Additionally, it operated 11 distribution or fulfillment centers, and more than 100 final-mile cross-dock centers. The news release announcing the acquisition's completion said Innovel would continue to serve existing third-party customers.
The growth in delivery demand for bulky goods has also driven other trucking companies to acquire last-mile providers and bolster existing services.
In November 2020, J.B. Hunt purchased Mass Movement, which had delivered more than 2 million equipment pieces to 3,500 fitness centers, one of four final-mile M & As the company had made since 2017. And FedEx expanded the coverage of its FedEx Freight Direct service in 2019 to deliver large items into more homes and businesses.
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Topics covered: logistics, freight, operations, procurement, regulation, technology, risk/resilience and more.
Businesses can't evade the trucking market, but there are strategies they can adopt to lessen the impact of market forces.
FedEx and UPS recently raised rates by 5.9%. But that doesn't factor in the sting shippers could face from surcharges, experts say.
Topics covered: logistics, freight, operations, procurement, regulation, technology, risk/resilience and more.
Topics covered: logistics, freight, operations, procurement, regulation, technology, risk/resilience and more.
Businesses can't evade the trucking market, but there are strategies they can adopt to lessen the impact of market forces.
FedEx and UPS recently raised rates by 5.9%. But that doesn't factor in the sting shippers could face from surcharges, experts say.
Topics covered: logistics, freight, operations, procurement, regulation, technology, risk/resilience and more. | general |
Covid continues to have a big impact on aviation emissions | First the pandemic, now the war. Long-distance flying was not expected to recover until 2024, but now the wait could be longer. As a result, aviation emissions are decreasing.
By Dave Keating
In January 2022, the European Travel Commission, a tourism promotion organisation, had good news and bad news for the aviation industry. The good news was that its research showed air travel within the EU was predicted to recover to pre-pandemic levels by the end of 2022. The bad news was that long-haul intercontinental travel would not recover until 2024.
The worst of the pandemic may be over, for now, but consumers are still feeling nervous about booking expensive long-haul trips. Not only is there the concern about having to cancel them, there are also more onerous vaccination and testing requirements for destinations outside one’ s own country, or outside the EU in the case of Europeans. Travel within the EU has been relatively hassle-free for the vaccinated, but outside of the EU has been a different story. The same pattern is being observed in the US – people prefer to take inter-state trips and are wary of leaving the country.
Now, the war in Ukraine looks set to extend this trend further. People generally shy away from international travel during periods of insecurity, and this is the most intense period of insecurity for Europeans since the Second World War. Flights between Europe and Asia will have to be diverted around Russian airspace, adding extra time and cost. Combined with the intense increase in jet fuel prices, we seem to be returning to an era where international flights are unaffordable for most people – at least for the next few years.
Long-haul flights do far more climate damage than short-haul, both because they are longer and because the planes fly higher. Although they make up just 6% of the flights leaving European airports, long-haul flights departing Europe produce more than half of the continent’ s aviation emissions, according to European air traffic management organisation Eurocontrol.
Related
After increasing rapidly over the past two decades, global CO2 emissions from aviation fell by one-third in 2020 compared with the previous year, according to the International Energy Agency. Emissions were just over 600 million tonnes in 2020 – the lowest level since 1997. The expectation was that this is a temporary phenomenon and growth will return to previous levels quickly. It is now clear that will not be the case. Aviation emissions continued to fall in 2021 even as the short-haul market in, for example, the US or EU, started to recover. The reason? Long-haul flights were not recovering – and still aren’ t.
“ One of the biggest contributors to reduced oil demand during the pandemic has been reduced flying, ” says Andrew Murphy, aviation manager for NGO Transport & Environment ( T & E) in Brussels. “ People are taking to their cars in a pretty standard way, but they are not doing long-haul travel. ” As airlines were receiving bailouts in 2020, Murphy and other campaigners were frustrated that virtually the only green condition placed on airlines was the scrapping of short-haul domestic flights in France and Austria.
It now seems the market is delivering an aviation emissions reduction where policymakers failed. The reason is not only that people are wary of booking far-away vacations – it is also the disappearance of business travel.
“ During Covid, we have found creative ways to do business meetings without face-to-face travel – Zoom is the most high profile, but we have also seen robotics and drones do on-site inspections, ” says Murphy. “ Both the [ new ] Covid variants in 2021 and now the Ukraine conflict in 2022 have highlighted the risks of relying on face-to-face long-haul travel. You don’ t know what the next crisis is going to be. ”
In Match 2022, T & E is planning to launch a corporate travel campaign around reducing long-haul aviation. “ A lot of companies are adopting pledges for the future, such as a 15% reduction in business travel, '' says Murphy. `` It isn’ t enough, but that is still a pretty significant impact on the sector because a majority of emissions are from long haul. ”
The changing demand has had an effect throughout the aviation supply chain. Long-haul routes have been cut, so aircraft-makers are ditching plans to make more large two-aisle planes in favour of smaller one-aisle planes. Many wide-body planes are sitting idle, with more than 1,400 of them in storage in aircraft hangers at the start of December 2021, according to the aviation consultancy Cirium. That is almost 30% of wide-body aircraft, down from 3,586 at the peak of the pandemic but still very different from the situation for smaller planes, where most have now been taken out of storage.
When will it be time to put these wide-body jets to use again? Anyone who made predictions last month has had those plans upended by the Ukraine war. “ The industry itself [ … ] was already admitting it would be the middle of this decade before travel would bounce back, ” says Murphy. “ If that is what they are saying in public, I think the reality is probably later.
“ It is a very exposed sector and its necessity has been shown to not be as high as the sector thought, ” he adds.
Nevertheless, many aircraft orders were placed years ago and still need to be delivered, and airlines are still flying some long-distance routes – even if they are empty – to hold onto their airport slots. More than 100,000 of these ghost flights will have been made by the end of this winter in Europe alone, according to environmental campaign group Greenpeace, equivalent to the yearly emissions of more than 1.4 million cars. They want the EU to change the laws around holding onto airport slots, something the European Commission has tried to do for years without success.
“ It would be irresponsible of the EU to not take the low-hanging fruit of ending ghost flights, ” says Greenpeace spokesman Herwig Schuster.
There is still more supply of than demand for long-haul flights. Wide-body planes are still being delivered to airlines and those airlines still want to hold onto their airport slots. “ Whilst deliveries of new generation aircraft continue, the pandemic has hampered the pace at which they can enter service, ” comments aviation advisory and analytics company IBA.
“ As the recovery begins to ramp up through 2022 and beyond, IBA expects operators will continue to reactivate their dormant fleets. This is likely to result in the global [ aviation ] emissions figure creeping up slightly. ”
The question is whether regulators, and the industry, can preserve the gains made in reducing aviation emissions during the pandemic. According to the International Council on Clean Transportation ( ICCT), an independent non-profit, it is unrealistic to expect the pandemic to impact long-term growth in passenger numbers. However, it could reshape the trajectory of that growth, from a high-growth scenario of a 3.7% increase in passenger traffic per year from now to 2050 to a low-growth scenario of 2.4%.
“ The Covid-19 pandemic reminds us that no one can predict with certainty what the air travel industry will look like in ten, 20 or 30 years, ” says the ICCT’ s Brandon Graver. | general |
Op-Ed: The rise of the holobricks – 3D holograms are coming | Hi, what are you looking for?
The potential is there for reliable complex 3D imaging in real-time.
By
Published
We’ re not on the holodeck yet, but it’ s definitely coming. New “ holobricks ” are able to create strong high-def images in 3D. Each holobrick has roughly the same parameters as a laser-accurate screen image: “ 1024×768 pixels, with a 40° field of view and 24 frames per second ” for tiled 3D images.
If those numbers look familiar, they should. They’ re standard screen dimensions. Note the field of view and the frames per second. Standard fps is 60fps for video images, for example. This is still a hologram, not a standalone solid image, but it’ s getting there.
The technical name for holobricks is “ spatial tiling of multiple coarse integral holographic ( CIH) displays ” according to Nature.com. Most of the information available is largely about technical specifications and the surprisingly straightforward math behind making the holobricks work. ( It’ s ratios, basically.)
These are early days, but there’ s obviously a lot more to come, and sooner rather than later. It’ s easy to see artificial intelligence doing the lethal number-crunching required to enhance the properties of the holobricks.
It’ s also easy to see how existing top-quality cinematic gaming software could fill in a few blanks for motion. You’ d simply need to add the extra dimension ( s) to the field of view in motion, reciprocal interactions, etc. for a 3D version of Fortnite.
No money in that, obviously. I mention gaming because it’ s a huge capital-rich market for high-end visuals. The gaming sector also has the hands-on experience of some of the world’ s better thinkers. They could probably turn holobricks into the visual equivalent of LEGO, and as easy to work with.
The current state of holobricks indicates a degree of pre-natal clunkiness in some unavoidable areas. You could solve that with “ nano pixels ” ( component pixels in a pixel) to improve resolution. This is tweaking, really, and the fine-tuning is essentially just all “ make it look right ”.
The future is huge
Holobricks could become incredibly high-value tech simply because of the vast range of possible uses. Media is the obvious use; other uses may include:
…Ad infinitum. The potential is there for reliable complex 3D imaging in real-time. 2D isn’ t, and can’ t, be the same. Anywhere you need good information, 3D imaging will be better and more informative.
Aesthetics and lifestyle
Holobricks could be god’ s gift to living spaces, as well as media companies, arts, and sciences. Holobricks have another, almost Utopian, application in living spaces. Wan na transform your current palace into something really “ you ”? It’ s doable. Feeling a bit Baroque or Dada, Goth or Impressionist? Need to go to Mars without all that travel? Project it with inset projectors. Change the entire living space with a bit of software.
Need a less murderous living space? Include stuff you like. Even a dismally decorated apartment aka cupboard will look and feel better. Sick building syndrome also includes décor, unforgiving color schemes, etc. So now you can fix that.
Want to hold a theme party? Use a top-of-the-line 3D holo-theme. How hard could it be? In larger areas, you could do almost anything.
So do it.
Disclaimer:
The opinions expressed in this Op-Ed are those of the author. They do not purport to reflect the opinions or views of the Digital Journal or its members.
Editor-at-Large based in Sydney, Australia.
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Peaky Blinders star Amber Anderson on what it's like to join the biggest show on TV | We earn a commission for products purchased through some links in this article.
Stepping onto set for her first day starring in the final season of Peaky Blinders, Amber Anderson had just one thought: Anything but that scene. But as the 30-year-old Glastonbury-born actor pored through the schedule for her first week as the show's latest sinister and scheming villain, she got the news she had been dreading.
`` My first day was the one scene I really didn't want to start with, '' she tells Cosmopolitan UK. `` You always have that one scene in the script that you hope isn't the first one you film - but of course that was the one.
`` It's quite a long monologue, with just me speaking to a room full of people. So, I had first day nerves anyway, combined with the cold, combined with the fact all the doors were open [ for Covid safety measures ], combined with the fact I had all these layers on [ she estimates about seven ] combined with having to do fake smoking. I remember doing this scene and trying to look really cool and graceful and like I was from the 1930s and as I brought my cigarette up to my mouth my hand was just trembling. ``
TV and film sets can be intimidating places, particularly when casts are as established as this one, made up of big names like Cillian Murphy and Tom Hardy. If that weren't enough to make your petticoated knees wobble, Peaky Blinders is one of the most popular shows on TV right now ( during lockdown it was Netflix's most binged show), and this is its final series - its legacy hangs in the balance.
And yet, even with all that pressure, on a freezing cold set in a ramshackle Victorian house on the outskirts of Manchester, every door and window thrown open as part of the set's coronavirus measures, Anderson says that behind the scenes on Peaky Blinders is one of the calmest, most down to earth sets she has ever been on.
`` I was almost surprised at how welcoming everyone was. It was a show that already has its way of working so I felt quite nervous coming in as the new guy, but everyone was just really nice.
`` Cillian was so lovely to meet because he's just so normal. On my first day he was just very quietly standing at the side of the room watching everything... and it just struck me how down to earth and kind he was.
`` I think the way a leading actor is really trickles down to the rest of the set, so it meant the whole set felt quite normal and down to earth. There were no big egos, it was like a group of friends. ''
That's not to say that there weren't slip ups. There are things about being on a show like this one that you 'd never even consider until the cameras start rolling.
`` Because the scenes are so serious I think it actually creates more space for banter. You 'd have these very serious scenes that would be interrupted by someone's cigarette lighter not working or the time someone almost set my wig on fire.
`` There was a very funny moment in a scene between Ada ( Sophie Rundle) and I, where I had to pour us glasses of whiskey and it quickly became obvious that I 'd never poured a glass of whiskey before. I poured an entire tumbler-full - like it was a glass of juice - and everyone on set started laughing. ''
It's not just the drinking, smoking is something a lot of the cast have had to slightly re-learn while filming the show. The cigarettes are herbal replacements, specially designed for long days on set, ( Cillian Murphy reportedly smokes around 3,000 of them per season) and containing none of the usual ingredients. But, that doesn't make it easy.
`` There's no nicotine or tobacco in them but there's still something you have to inhale, so it was a strange shock for my body because you light a cigarette at the beginning of every take, and you might do 10 different takes and maybe seven different camera set ups. So, I did end up with a few headaches. ''
Anderson's character, the quietly evil Diana Mitford, was first introduced in episode two of the series. In just under two minutes she and her fascist partner in crime sent chills down the spines of viewers and Shelbys alike.
The real life Mitford married fascist politician Oswald Mosley at the Berlin home of Joseph Goebbels in 1936, with Adolf Hitler in attendance as the guest of honour. How you go about becoming a such a grotesque character today is a challenge plenty of actors would struggle with, but in Anderson's first scene the couple's repugnance is palpable, not least with how Diana so delicately belittles Lizzie in her first scene.
As Diana puts it, `` By the way, I really don't like 'Lizzie ', I prefer 'Liberated Elizabeth '. She must be part of this. She's been all the way to Paris so she is a woman of the world, bravo. ''
Anderson explains, `` My role is pretty dark, she's definitely someone who's there to disrupt and cause havoc. Getting into a character like that is actually quite fun because it's so far away from who I am naturally. A lot of it came down to the clothes, the makeup, the wig and the research.
`` I 've almost always played women who cared a lot about being liked and so I would automatically bring that energy to set with me, whereas with [ Diana Mitford ] she doesn't care at all if she's liked or not. I could come to set with a slightly more nonchalant attitude. ''
Anderson researched Mitford for more than three months before taking on the role, but she had to keep her character a secret - no mean feat in the world of Peakys fandom, one of the most ardent and thorough out there.
`` I kept getting comments [ from fans on Instagram guessing her character ] that make sense and then I get a lot of comments saying 'Maybe she's playing Gina's mother, ' and I 'm just like 'How dare you! I 'm only three years older than Anya [ Taylor-Joy ]! I 'm only 30, '' she laughs.
Before she joined the cast Anderson was as much as a fan of the show as the rest of us. So, when the chance to audition came up - alongside `` every actress in London '' - it was a no brainer. After all, as the sixth and final season, this is her last chance to be part of the Peakys family. When the show ends it 'll bring about a double edged grief for its cast who must wave goodbye to the characters and the world they have all loved so much as well as the show itself that many of them were historically fans of. That is, until the film...
`` You could tell on set that all the actors were looking through the script going, 'Do I die? I don't, that's interesting... ', but at this point it's pure speculation.
`` Nobody knows what's happening, as far as I 'm aware it's just at an ideas stage, and no one knows who's in it or what it is - apart from Cillian, obviously. ''
Peaky Blinders series 6 continues on BBC iPlayer every Sunday at 9pm. | general |
Energy Crisis Has Much to Learn From 1973 | Mark Twain reputedly said that history does not repeat itself but often rhymes. Indeed, the Ukraine war seems to echo the 1973 Yom Kippur War in its dire energy consequences. The 1973-74 oil embargo and skyrocketing prices caused most OECD governments to decide drastic policies and implement them quickly without significant backlash. This happened again in 2020 when the Covid-19 pandemic broke out. But the oil crisis also shows that policies set half a century ago have mostly survived regardless of how oil prices have evolved. Today, while short-term options are readily available to substitute Russian imports, the crisis could trigger decisive longer-term policies to expedite the world's low-carbon transition.
It took Western Europe about 15 years to halve its oil consumption per dollar of GDP, which is now 70% -75% lower than in 1973. This is the kind of effort the world would need to make again in the next 10-20 years in terms of carbon emissions if it wants to achieve the Paris agreement's 1.5°C target.
The oil embargo and high prices caused OECD countries to deploy savings plans unheard of in times of peace. Some measures were short-lived, such as gasoline rationing in many countries, the introduction in the Netherlands, Belgium and Switzerland of car-free Sundays, or the requirement in France for offices to switch off lights after 10 p.m. and TV stations to stop broadcasting after 11 p.m. The UK, which was also facing a coal miners ' strike, introduced the three-day week, in which commercial use of electricity was limited to three consecutive days each week to reduce power consumption.
Similarly, in the case of a potential Russian energy embargo in today's context, quick policy measures would minimize costs for Europe because gas demand is seasonal, a group of German economists insist in a new report on the economic impact of stopping Russian energy imports. An early move would allow `` Norwegian and other sources '' to take over more easily during the summer months while keeping European industrial production going. It would also `` immediately trigger the substitution and reallocation dynamics that are central to reducing economic costs. '' Those would amount to around 2.5% of GDP or €1,000 ( $ 1,100) per German citizen over one year, which is significant but bearable, and substantially lower than Germany's 4.5% GDP decline in 2020 during the peak of Covid-19.
Substituting Russian imports of oil and coal would `` likely not pose a major problem, '' the report's authors note. Likewise, gas that is currently used for power generation could easily be saved by switching to coal — and possibly nuclear — and reallocated to other users. Those would have to save or substitute energy — or, for industrial companies, to reduce production — but this would be limited, the report finds.
Beyond immediate emergency measures, many policies launched during the 1973 crisis have either already made a marked long-term impact — or they provide useful models for decision-makers to follow and repeat. Road speed limits were introduced in many places in response to the crisis five decades ago, which are still in place or have been intensified. In the Netherlands, for example, the daytime motorway speed limit was recently lowered from 130 kilometers per hour to 100 km/h to reduce CO2 emissions. Similarly, energy conservation was promoted throughout OECD countries, for example with the US ' Corporate Average Fuel Economy standards for new cars, which were enacted in 1975.
In France, people were encouraged to reduce heating temperatures to 20°C. This was turned into law in 1974 for public housing, schools, offices and commercial buildings, and later tightened even further to 19°C. Today, a strict EU-wide enforcement of that temperature — down from the current 22°C average — could save the EU 20% of its Russian gas consumption at almost no cost, according to International Energy Agency ( IEA) data.
The 1973 energy crisis also led to greater interest in alternative energy sources, notably nuclear power. The most remarkable example, which is often cited as a model for global renewable deployment to follow, is the French nuclear program. France had launched an ambitious plan in the late 1960s to address its lack of fossil fuel resources, which was targeting 13 gigawatts of new capacity to be commissioned over 1972-77. The oil crisis caused a dramatic inflation in ambitions, with an additional 50 GW to be developed over 1974-80 and a long-term target of around 150 GW by 2000.
This was revised in the mid-1980s as low economic growth and better energy efficiency made it clear power demand was not growing as fast as expected. But France managed to commission 63 GW of nuclear capacity over 1978-99, or an impressive 3 GW per year during 21 years. The share of nuclear in French electricity production has reached 75% in 1990, up from just 8% in 1973. The IEA's net-zero scenario similarly assumes wind and solar energy should reach 70% of global power generation by 2050, up from just under 10% now. | general |
Apple supplier Foxconn sees possible revenue hit from supply chain woes | The Taiwanese company, which had stopped production in China earlier this week to comply with government curbs, said separately that it had restarted some production and operations at its Shenzhen campus after meeting government conditions for staff to live and work in a bubble.
The stoppages from Foxconn - the world's largest contract electronics maker - and other companies including Japan's Toyota Motor have fuelled concerns over how global supply chains could be impacted as China deals with its biggest spike in COVID-19 infections since early 2020.
Chairman Liu Young-way said on a post-earnings call on Wednesday that Foxconn would only have better clarity on supply chain uncertainty in the second half of the year.
He said the record-high revenue in 2021, boosted by booming electronics demand following the pandemic, would lead to `` stable '' business this year due to a high base last year.
`` The pandemic has not eased, inflation is high and global politics are getting tense - these all further complicate supply and demand and lead to great uncertainty to our outlook, '' Liu said, calling 2022 a `` very challenging year ''.
Still, Liu said he was `` cautiously positive '' about the company's 2022 sales outlook, citing continuous growth from sectors including 5G smartphones and cloud products.
He had previously warned that he expected the chip shortage to run into the second half of 2022.
Liu said on Wednesday that Foxconn expected limited impact from the war in Ukraine, echoing Taiwan's government which says any impact on the island's supply chains would be small because Russia and Ukraine are not the main import sources of raw materials such as nickel and neon.
Apple has paused all product sales in Russia in response to the invasion, which Russia calls a special military operation.
Foxconn, formally called Hon Hai Precision Industry Co Ltd, said it expected revenue for the first quarter as well as the year to range between a 3% fall and a 3% rise. Analysts expected revenue this year to rise 1.2%.
The company forecast smartphone revenue to be flat in 2022.
EV PLAN
Foxconn has in recent months announced plans to become a major player in the global electric vehicle ( EV) market. On Wednesday, it said it doesn't expect revenue from EVs to be significant until 2023.
Foxconn, which has EVs deals with a variety of companies including Lordstown Motors Corp, forecast an annual production of up to 750,000 units by 2025.
In the fourth quarter ended December, Foxconn's revenue fell 6%, its first decline in five quarters, though still the second-highest for the quarter.
Revenue from its key smart consumer and electronics products business fell between 3% to 15%, in the period. Smartphones account for 60% of this business.
Revenue from its cloud and networking products as well as computing products was flat. Components revenue rose more than 15%.
Foxconn shares closed 0.5% higher ahead of the earnings release, versus a 0.1% gain in the broader market. They have fallen 2.4% so far this year.
Net profit fell 3.4% to T $ 44.4 billion ( $ 1.55 billion) in the October-December period. That compared with the T $ 43.32 billion average of 10 analyst estimates compiled by Refinitiv.
( $ 1 = 28.5700 Taiwan dollars)
( Reporting By Yimou Lee and Ben Blanchard; Editing by Sayantani Ghosh and Muralikumar Anantharaman)
By Yimou Lee and Ben Blanchard | business |
Audi's Neckarsulm plant stops production on supply chain disruption | BERLIN -- Audi’ s Neckarsulm plant in Germany has been forced to shut down production since the beginning of the week, an Audi spokesperson confirmed to Automotive News Europe.
Supply bottlenecks caused by the war in Ukraine and the coronavirus pandemic, as well as the current situation regarding the supply of semiconductors, are contributing factors.
Production of the A4 and A5 models has been at a standstill in Neckarsulm since Monday. Production of the A6 and A7 models has been stopped since March 7.
Production will be paused until Friday, March 25. | general |
Mercedes vows EV push despite Ukraine disruptions | The crisis has sent gas and mineral prices skyrocketing, challenging the production of both fossil fuel and electric-powered vehicles.
However, speaking at the opening of Mercedes ' first U.S. EV battery plant in Alabama, CEO Ola Kaellenius said it was working around the clock to minimize production disruptions and that its financial outlook was still strong.
`` We always protect the investment into future technology and future products. That is the seed that we will later on harvest and not even in the COVID year of 2020 did we cut back on the R & D ( research and development) side for the crucial future projects. ''
The Alabama plant will employ 600 workers, part of a $ 44 billion drive by Mercedes to go all electric by 2030, where markets allow.
Kaellenius says the war is not stopping Mercedes from making that EV shift, and previewed a large electric SUV to be built at a nearby facility in the city of Tuscaloosa later this year.
`` Opening up this battery plant here in Alabama today is a big step in our electrification strategy, and in fact, you can see last year we announced that we think electrification is going to come faster. So, we intend to ramp up faster and be ready by the end of this decade to go all-electric in markets where the market conditions allow. ''
With the new EVs, Mercedes is joining a growing lineup of electric carmakers seeking to challenge Tesla in the U.S., China and Europe.
However, Mercedes and other established automakers still trail Tesla in EV sales and the development of new computer and software systems. | business |
WTO Chief Hails Covid Vaccines IP Compromise | The World Trade Organization chief hailed Wednesday a breakthrough between the EU, the United States, India and South Africa on waiving intellectual property rights on Covid-19 vaccines.
Ngozi Okonjo-Iweala said the compromise was a big step forward in a bid to end the logjam at the global trade body.
However, she cautioned that some of the details on waiving WTO rules on Trade-Related Aspects of Intellectual Property Rights ( TRIPS) still needed to be fleshed out -- and it would need the backing of all WTO members to come into force.
`` This is a major step forward and this compromise is the result of many long and difficult hours of negotiations, '' Okonjo-Iweala said.
`` But we are not there yet. We have more work to do to ensure that we have the support of the entire WTO membership. ''
Since October 2020, South Africa and India have called for IP rights to be temporarily lifted for coronavirus vaccines during the pandemic in order to boost production and address the gaping inequality in access between rich and poor nations.
However the idea has met with fierce opposition from pharmaceutical giants and many of their host countries.
They have argued that patents are not the main roadblocks to scaling up production and warn the move could hamper innovation.
Okonjo-Iweala's statement came hours after Adam Hodge, spokesman for the US Trade Representative Katherine Tai, announced that lengthy talks had resulted in a `` compromise outcome that offers the most promising path toward achieving a concrete and meaningful '' result.
`` No agreement on text has been reached and we are in the process of consulting on the outcome, '' he added.
Okonjo-Iweala, a former Nigerian finance minister, said should start immediately to widen the discussion to all 164 WTO members.
Switzerland, home to several major pharmaceutical companies, has notably repeatedly voiced its unwillingness to budge.
A source close to France's foreign trade minister Franck Riester said agreement had been struck at a technical level but now needed a green light at the political level.
He said the compromise would only apply to developing countries accounting for less than 10 percent of global Covid vaccine exports, excluding China.
He said the plan was intended to facilitate the granting of compulsory licensing deals, a provision already within the TRIPS system.
Compulsory licences give companies other than the patent holder authorisation to make a product, without the consent of the patent owner, subject to certain procedures and conditions being respected.
The International Federation of Pharmaceutical Manufacturers and Associations big pharma lobby group slammed the compromise, saying that weakening patents when supply constraints had eased was a mistake.
The IFPMA said 12 billion vaccine doses had been produced within a year of the first jab being authorised, and the industry was now pumping out more than a billion doses per month.
`` The challenge now is how to get the vaccines into the arms of people who need them, rather than vaccine supply, '' the group said.
`` The TRIPS waiver is not only the wrong solution, it is also an outdated proposal, that has been overtaken by events. ''
Max Lawson, co-chair of the People's Vaccine Alliance coalition campaigning for wider access to Covid vaccines, said the TRIPS waiver proposal was a half-measure that did not address IP rights on Covid-19 treatments. | business |
Fourth Covid Shot Provides Little Benefit Against Omicron Infection: Study | A fourth dose of existing mRNA Covid-19 vaccines may have only `` marginal benefits '' for younger, healthy adults, according to a new Israeli study published Wednesday in the New England Journal of Medicine.
The research assessed 270 health care workers at the Sheba Medical Center in Tel Aviv who received a second booster shot of either the Pfizer or Moderna vaccines, four months after initially getting three Pfizer shots.
Each was age-matched against two participants in a control group that had received only three doses of Pfizer, with the median ages in the groups ranging from mid-fifties to early sixties.
Overall, the fourth shot was found to be safe, and topped up recipients ' neutralizing antibodies -- which block the coronavirus from infecting cells -- to levels comparable to just after the third dose, prior to when antibody levels started waning with time.
The study took place when spread of the Omicron variant was rife in Israel, and it found that the fourth dose didn't confer much added protection against infection, despite the reduction over time of antibodies among people who 'd received just three shots.
Those who got a fourth shot of Pfizer were 30 percent less likely to acquire infection than those who got three doses, while those who got Moderna were 18 percent less likely to get infected.
The study included only a small number of participants and was not a randomized trial -- meaning its conclusions should be interpreted with caution -- but the results point towards only minor benefits from the extra dose.
Protection against symptomatic infection was slightly better in under-40 adult recipients of a fourth jab -- 43 percent for Pfizer and 31 percent for Moderna -- compared to people who received three shots.
The study authors, led by Gili Regev-Yochay, wrote that their research seems to indicate the advantages of three doses of vaccine designed against the original strain of coronavirus had hit a ceiling in terms of immune response, with additional boosters only restoring waned immunity, rather than taking it to new heights.
`` Furthermore, we observed low vaccine efficacy against infections in health care workers, as well as relatively high viral loads suggesting that those who were infected were infectious. Thus, a fourth vaccination of healthy young health care workers may have only marginal benefits, '' they said.
Outside experts said the findings showed the need to develop new vaccines.
`` If Omicron continues circulating and we are still using the current first-generation Covid-19 vaccines against it, then I agree with the authors that the benefits to otherwise healthy, younger people will be marginal, '' said Julian Tang, a clinical virologist at the University of Leicester.
`` Any fourth dose boosters will be more beneficial to the older and more vulnerable groups ( e.g. those with comorbidities), '' he continued. | business |
UPS, Amazon & FedEx top North America logistics firms chart | CSX is a leading supplier of rail-based freight transportation based out of Jacksonville, Florida. As a railroad, the company operates around 21,000 route miles of track. The company was formed in 1981 by combining the railroads of the former Chessie System, Seaboard Coast Line Industries then the Seaboard System Railroad in 1986. The brand is currently valued at $ 4bn.
With a brand value of $ 4.4bn, CN Logistics is a Canadian-based transportation company that offers integrated services covering rail, intermodal, trucking, freight forwarding, warehousing and distribution. CN has approximately 24,000 railroaders and transports more than $ 250bn worth of goods annually for an array of business sectors, ranging from resource products to manufactured products to consumer goods, across a rail network of approximately 20,000 route-miles spanning Canada and mid-America.
The McLane Company is one of the largest supply chain service leaders providing grocery and foodservice supply chain solutions for convenience stores, drug stores and more in the US. It has one of the largest private fleets in America and delivers around 50,000 products to 110,000 locations and employs around 20,000 employees. The President and CEO of McLane since 1995 is W. Grady Rosier and its brand value is currently $ 4.8bn.
Union Pacific is a freight hauling railroad that operates 8,500 locomotives consisting of 43 different models, operating over 32,100 route miles. Its system is the second biggest in the US. The company started in back in 1862 when it was called the Union Pacific Rail Road and its current CEO is Lance M. Fritz. The brand value of the company is thought to be $ 7.8bn.
As one of the largest transportation logistics firms in North America, JB Hunt offers an integrated, multimodal approach and offers capacity-orientated solutions centred around driving customer value and industry-leading service.
The company offers full truckload transportation, container and trailer transportation, customised freight transportation, revenue equipment and customised labour and system services.
Considered a pioneer in the logistics space, its intermodal approach operates a fleet of company-owned 53’ containers and drayage fleets in North America. The company has a range of long-standing relationships with major rail providers, including the likes of BNSF, Norfolk Southern, CSX and CN to ensure capacity.
CH Robinson solves logistics problems for organisations all over the world and across a range of industries. It is considered one of the world’ s leading logistics platforms and operates almost US $ 20bn in freight under management and 18 million shipments annually. It serves a diverse range of markets, including North America, Asia Pacific, EMEA, South America and Oceania.
US global shipping and contract logistics services organisation XPO Logistics boasts 1,530 sites in 30 countries. It is responsible for the supply chains of 69% of Fortune 100 firms. Specialty areas include freight brokerage, intermodal and drayage ( short-distance logistics), last-mile distribution, and global forwarding. KN Integrated Logistics is its supply chain arm, and areas it handles include supplier and inventory management, aftermarket management and supply chain Technology. XPO’ s headquarters are in Greenwich, Connecticut.
It serves a range of industries, such as automotive, manufacturing and healthcare, among many others. The firm has three main international freight forwarding solutions, featuring its Ocean and Air Freight, in addition to its Global Order Logistics solution.
Based in Memphis, Tennessee, FedEx is a US global freight company. It was founded in 1971 as Federal Express, and was a specialist in expedited deliveries. FedEx is the world's largest cargo carrier in terms of scheduled freight tonne kilometers, and the fourth largest in terms of fleet size. The company has operations in 220 countries and has 3,000 metres squared of warehouse space. Its revenue in 2020 was US $ 69mn.
FedEx Supply Chain, is a 3PL provider in the US and Canada. Industries it serves include: technology and electronics, retail and e-commerce, consumer and industrial goods, and healthcare industries.
FedEx today, is best known for its air delivery service, FedEx Express. It was one of the first major shipping companies to offer overnight delivery as a flagship service.
Amazon Logistics is a shipping and delivery service that complements existing third-party logistics ( 3PL) providers such as UPS, USPS and FedEx.
Amazon stipulates certain conditions for its 3PL providers, including licensing, vehicle sizing, safety training and insurance. The 3PLs providers are contracted to pick up deliveries at Amazon warehouses and sorting centres for distribution. They use Amazon tech to guide their deliveries, but they enjoy flexible schedules and pick up shipments at-will.
It offers seven-day and same-day delivery options, and utilises a host of third-party logistics partners across the country to make it happen, including walkers, bicyclists and motorcyclists in some areas.
US-based parcel delivery service UPS ( United Parcel Service) has been around for more than a century, having been founded in 1907 as a messenger service operating out of Seattle. The company specialises in shipping, air freight, trucking, last-mile distribution, and drone delivery. It now has its HQ in Atlanta, Georgia.
UPS has more than 35 million sq ft of distribution and warehousing facilities in 1,000 locations that are based in 120 countries. In all, it serves 220 countries and territories. It is the largest courier company in the world by revenue, with US $ 85bn in 2020, ahead of competitors DHL and FedEx.
In 2021 - following a shift to smaller customers during the Covid-19 pandemic, UPS reported a 21% jump in Q $ sales, to US $ 24.9bn.
Meet David Lawson Director of Procurement at Guy's & St. Thomas ' NHS Foundation Trust. Lawson will be speaking on Day 1 of Procurement & Supply Chain LIVE…
Supply Chain Digital is the digital community for the global supply chain & logistics industry that connects the world's largest supply chain & logistics brands. Supply Chain Digital focuses on procurement and supply chain news, key interviews, supply chain videos, along with an ever-expanding range of focused procurement and supply chain white papers and webinars. | general |
Oil futures: Markets slide from highs on Iran talks and demand fears, Brent around $ 100/b | Crude oil futures Wednesday were off from the highs as markets gave up earlier gains on China's rising Covid cases and progress on the Iranian nuclear talks, having initially posted firm gains as Russia's invasion of Ukraine continued with no sign of an immediate ceasefire.
Front-month May ICE Brent futures were trading at $ 100.17/barrel ( 1245 GMT), compared to Tuesday's settle of $ 99.91/b, but off from Wednesday's high of $ 103.70/b.
At the same time, April NYMEX WTI was trading $ 97.35/b, versus Tuesday's settle of $ 96.44/b, as futures contracts continued to experience sharp price swings.
Russia's Foreign Minister Sergey Lavrov said Tuesday that Moscow had received guarantees from the US on its ability to trade with Tehran as part of ongoing talks to salvage the Iran nuclear deal, which analysts see as a potential path to resuming the 2015 nuclear accord.
`` This appears to remove one major obstacle to the revival of the 2015 nuclear agreement, paving the way for US sanctions against Iran to be lifted and thereby allowing Iranian oil exports to resume, '' said Carsten Fritsch of Commerzbank.
Meanwhile, China has reported Covid cases in 21 provinces, leaving over 35 million people in lockdown as of Wednesday.
Ukrainian Presiden Zelensky said on Wednesday peace talks with Russia were sounding `` more realistic '' but that more time was needed for any deal to be in the interests of Ukraine.
US President Joe Biden will travel to Brussels next week to meet with NATO allies about bolstering support for Ukraine as it fights to fend off Russia's unprovoked attack.
The `` extraordinary summit '' on 24 March will bring together leaders to discuss `` further strengthening NATO's deterrence & defence, '' NATO Secretary-General Jens Stoltenberg said.
Russian exports and potentially production remain under threat, although steep discounts have encouraged some buyers to continue purchasing spot Russian crude.
`` Given the weakness that we have seen in the market over the last week, it is clear that there is little risk premium priced into the market, which leaves it vulnerable to upward spikes if there is a deterioration in the Russia-Ukraine war, '' said Warren Patterson, head of ING's commodity research, noting Brent has fallen by around 28% since trading to an intraday high of US $ 139.13/bbl back on 7 March.
OPEC said Tuesday that it still expected oil demand to rise by 4.2 million bpd in 2022, a 20% slowdown in growth year-on-year, but warned that a slowdown in economic growth due to higher inflation and the war in Eastern Europe meant there was some downside risk. | general |
Restaurant Revitalization Fund Not In $ 1.5T Spending Bill | Restaurants still struggling to recover from the COVID-19 pandemic have been excluded from the $ 1.5 trillion omnibus fiscal year 2022 appropriations package signed by President Joe Biden, industry advocates say.Congress in passing the omnibus spending package last week for all federal government operations did not allow for replenishment of the hard-won 2021 Restaurant Revitalization Fund, or RRF, grant program run by the Small Business Administration, which had provided eateries with a much-needed $ 28.6 billion, according to Sean Kennedy, executive vice president of public affairs for the National Restaurant Association. `` We are calling it a gut punch to those 177,000 restaurants... | general |
Closure of Russian shops presents challenge for new head of Zara owner Inditex | New Inditex chair Marta Ortega is the daughter of Inditex’ s founder Amancio Ortega.
Marta Ortega will start her job as chairwoman of her father’ s retail empire Inditex next month with an unenviable task: dealing without Russia, the Zara owner’ s second-largest market in terms of stores.
Her predecessor, Pablo Isla, is leaving the company after spearheading Inditex’ s expansion over 17 years.
He paid a special emphasis to Russia, where the Spanish company has more than 500 stores, more than any other country besides Spain. Now, those are all temporarily closed in response to the war in Ukraine.
Ms Ortega, the 38-year-old daughter of Inditex’ s founder, faces a laundry list of challenges besides Russia.
Inflation and supply chain challenges are dimming the outlook for this year, while the resurgence of Covid in China threatens to weigh on consumption in another key market.
Meanwhile, cut-rate price online retailer Shein Group is steadily becoming a bigger competitor even as Inditex has been pumping €1bn into its own e-commerce business. | general |
Piling Concerns Brutalize Chinese Equities | Chinese stocks are posting their worst losses since 2008 with a myriad of headwinds in play including U.S. delisting fears, a new surge in Covid cases, sanction risks and more.
Already beaten down by an ongoing domestic crackdown on the tech sector – including the latest possible record high money-laundering fine against Tencent – Chinese stocks are undergoing an even steeper decline as of late.
The first of the new rounds of sell-offs was triggered by an announcement issued by the U.S. Securities and Exchange Commission last Thursday warning of the potential delisting of five companies – BeiGene, Yum China, Zai Lab, ACM Research, and HUTCHMED – if they fail to comply with auditing requirements under the Holding Foreign Companies Accountable Act enacted in 2020.
The Nasdaq Golden Dragon Index – a benchmark that tracks Chinese companies trading on U.S. exchanges – fell 10 percent, marking its worst drop in a single day since the 2008 global financial crisis.
« Uninvestable »
This week, Chinese equities posted more one-day record lows after a J.P. Morgan research note issued on Monday downgraded 28 internet firms to underweight, including Alibaba, Tencent Holdings and Meituan, calling them « uninvestable » over the next six to 12 months.
« Due to rising geopolitical and macro risks, we believe a large number of global investors are in the process of reducing exposure to the China internet sector, leading to significant fund outflows, » J.P. Morgan analysts said in the note, adding that the sector-wide sell-off could continue without valuation support.
« The tech sector will continue to suffer from regulation challenges plus the risk of U.S. delisting and penalization of growth stocks as rates continue to normalize, » added Cesar Perez Ruiz, chief investment officer of Pictet Wealth Management which is underweight Chinese equities and prefers developed over emerging market stocks.
Covid Resurgence
Furthering its challenges, China is experiencing its worst Covid outbreaks since Wuhan in various major cities with lockdowns and restrictions imposed in Shenzhen and Shanghai.
Combined with its insistence to maintain the zero-Covid policy, this could derail its growth target of 5.5 percent this year, an objective higher than analysts expected which was announced last week at the annual session of the National People’ s Congress.
« China is experiencing the largest wave of COVID since the end of national lockdown in March 2020, » according to a note authored by ANZ Research’ s Raymond Yeung and Zhaopeng Xing. « If the lockdown is extended, China’ s economic growth will be significantly affected. It is too early for us to change our GDP growth forecast ( 5.0 percent) for 2022 but we are wary of the impact of a partial lockdown in the economically rich provinces. »
« The sharp pick-up in Covid cases has put major cities such as Shanghai and Shenzhen into lockdown – with no suggestion that Chinese authorities are prepared to back away from their zero-tolerance stance to Covid, » according to an analyst note by ING.
Sanction Risks
In addition to ongoing property troubles and a new nickel crisis, China also faces the threat of Western sanctions.
Although it has publicly stated that it has no intentions to challenge the sanctions and its larger banks are avoiding such risks, there are concerns that Russia has reportedly asked China for military assistance, though the two countries deny the claims. If true, this could add further pressure to Chinese markets, including the technology sector which is increasingly involved in the defense industry.
« They have their own self-interest to not supply [ advanced technology ] to Russia, » said U.S. secretary of commerce Gina Raimondo in a recent « New York Times » interview, adding that Washington could « essentially shut down » China’ s largest chip maker Semiconductor Manufacturing International Corporation ( SMIC).
« So they’ re not doing it out of the goodness of their heart. It would be devastating to China’ s ability to produce these chips. »
Policy Support
Despite the risks, some remain optimistic that a rebound is within sight.
UBS, for example, is positive on Chinese equities due to policy support such as monetary easing and is forecasting the economy to trough in the first quarter before recovering throughout the rest of 2022, resulting in solid earnings growth and 5 percent annual GDP growth.
Coupled with lower valuations, UBS upgraded offshore Chinese equities to its most preferred market in Asia with expectations of high-teen returns for MSCI China this year. | general |
Concerns CCTV in Cork towns will need costly upgrades | There are 22 CCTV systems set up in the county, but only 15 are operational. Picture Denis Minihane
Community CCTV technology may have become outdated in a number of Co Cork towns because of the delay in deciding who views footage from them.
Some systems in place for several years have not yet become operational as no decision has been made on who will be the data controllers.
Concerns have also been raised that it will be very costly for local authorities if they are appointed data controllers and it has been suggested that Cork County Council, Cork City Council and Kerry County Council should club together to provide one central monitoring unit for their regions.
However, hooking up systems in these areas to just one viewing centre could be extremely expensive.
Sinn Féin councillor Danielle Twomey asked Cork County Council officials to seek an update on the pending data controller policy being decided by the Local Government Management Agency ( LGMA).
Ms Twomey told the Irish Examiner there are 22 CCTV systems set up in the county, but only 15 are operational.
Charleville, Mitchelstown and Midleton, for example, are not turned on. The money has also been ringfenced for others to go live, but this hasn’ t happened. ''
“ We were told at a Cork County JPC [ Joint Policing Committee ] meeting last year that a decision on data controllers was only a few weeks away. But we’ ve heard nothing since. As crime statistics start to rise again [ after the axing of Covid travel restrictions ] we need to progress the CCTV to keep our constituents safe, '' Ms Twomey said. | general |
Morgues overflowing as Hong Kong suffers deadly COVID-19 wave | Hong Kong – Workers in protective gear in Hong Kong carted the bodies of coronavirus victims into refrigerated shipping containers on Wednesday, as the city’ s morgues run out of space from a deadly omicron surge.
In under three months since the highly transmissible variant broke through, Hong Kong has recorded nearly a million infections and more than 4,600 deaths — the bulk of them from the city’ s unvaccinated elderly population.
A funeral industry representative told local media the soaring death toll had seen a crunch in the city’ s supply of coffins, with only 300 remaining and expected to be gone by the weekend.
Leader Carrie Lam acknowledged the supply issues during a news conference on Wednesday, and said two more shipments of coffins will arrive in Hong Kong from the mainland soon.
“ I learned from the Food and Health Bureau last night that they are endeavoring to arrange transportation ( of coffins) by water, ” she said.
She added that officials have been trying to help families concerned about post-mortem affairs, including how to retrieve bodies already transported to public morgues without a doctor issuing a death certificate.
“ We will try to find a way for the family to take the body back so that they can arrange the funeral soon. The crematoriums … have also been working day and night at full capacity, ” Lam said.
Outside Fu Shan Public Mortuary on Wednesday, workers in full protective gear moved bodies covered in black tarp from a truck into rows of shipping containers.
Researchers estimate the infection toll in Hong Kong is significantly higher than official figures, likely already reaching half its 7.4 million population.
A man stands at the entrance to a funeral parlor displaying coffins in Hong Kong on Wednesday, as the city battles a deadly wave of COVID-19. | AFP-JIJI
Lam has taken hits from all sides on her handling of the crisis, with her administration blamed for the spiraling deaths and unclear messaging about a potential lockdown and mass testing.
Chinese social media users have reacted angrily in the past few days, saying the spread of COVID-19 in the mainland is due to Hong Kong’ s sluggish epidemic response.
Tens of millions in mainland China were abruptly placed under stay at home orders this week, after the emergence of more than 3,000 daily new cases as Beijing battles to maintain its “ COVID zero ” strategy.
In nearby Shenzhen, all 17.5 million residents were locked down on Monday after an omicron flare-up in factories and neighborhoods linked to Hong Kong.
After photos emerged of maskless Hong Kong residents sunning at a beach — which drew vitriol from Shenzhen’ s netizens — authorities announced Wednesday that government-managed beaches will be cordoned off starting Thursday.
“ As we see a surge of people going to beaches, we have to take appropriate measures in order … to reduce the public’ s movements to ensure safety, ” Lam told reporters.
This new measure adds to Hong Kong’ s already strict distancing rules, including wearing masks while hiking and a ban on gatherings of more than two.
The embattled chief executive — whose job is up for grabs in a few months — has so far declined to say if she will run for another term.
The selection process was postponed to May because of the wave of COVID-19 cases, and any further postponement would be up to Beijing, Lam said. | tech |
Major Japanese firms offer higher pay raises, accepting shuntō wage demands | Many major Japanese automakers and electronics firms have fully accepted pay demands by labor unions, while major steel-makers and heavy machinery companies have revived pay-scale increases, as this year’ s shuntō labor-management wage talks reached their climax on Wednesday.
The companies offered bigger wage increases than they did in last year’ s talks as they recovered from the fallout of the COVID-19 pandemic, despite uncertainty in the outlook for the Japanese economy due to Russia’ s invasion of Ukraine.
The focus is now likely to shift to whether smaller companies will be able to raise wages.
Nissan Motor Co. has fully accepted its labor union’ s demands for a monthly wage hike of ¥8,000. Toyota Motor Corp. already agreed on March 9 to fully meet the demands of its labor union.
In a rare move for electronics makers, Hitachi Ltd., Toshiba Corp. and NEC Corp. have all fully accepted their labor unions’ demands, agreeing to a pay-scale increase of ¥3,000.
Panasonic Corp., Mitsubishi Electric Corp. and Fujitsu Ltd. agreed to a pay-scale increase of ¥1,500. Last year, major electronics makers offered an increase of ¥1,000.
Among major steel-makers, whose talks cover the coming two years, Nippon Steel Corp. offered a pay-scale increase of ¥3,000 for fiscal 2022 and ¥2,000 for fiscal 2023. There were no pay-scale increases by major steel-makers in fiscal 2020 and 2021.
Heavy-machinery manufacturers Mitsubishi Heavy Industries Ltd. and IHI Corp. revived pay-scale increases following no such rises last year, agreeing to a hike of ¥1,500.
Many labor unions increased their wage demands in this year’ s shuntō talks. The labor unions of electronics makers demanded a pay-scale increase of ¥3,000, up by ¥1,000 from the previous year.
The government is hoping for a wage increase of at least 3% in this year’ s shuntō talks. | tech |
Pfizer, BioNTech seek FDA clearance of 4th shot amid worries over next COVID wave | For the past few months, public health experts have been watching Israel, where the country's Ministry of Health was among the first to begin offering fourth shots to older people.
Israeli officials made that decision in January, during the height of omicron's spread. But the results have been mixed, making it difficult to tell how much of the general public might need another shot.
According to Pfizer, a large observational study that month found infection rates were two times lower — and severe illness rates four times lower — in people who 'd gotten another shot at least four months after their third injection. Yet, a smaller study in healthcare workers indicated that a fourth shot wasn't strongly protective against mild or asymptomatic infections.
Additionally, real-world data have shown an initial booster provides considerable protection against hospitalizations and deaths, though it may decline somewhat with time, according to a February study from the Centers for Disease Control and Prevention. It's also unclear whether a fourth shot would be more protective than one tailored to omicron, or whether there are any downsides to another booster. Some researchers have suggested frequent boosters might fatigue peoples ' immune systems.
In the meantime, pressure has begun to rise in the U.S. to prepare for future waves of COVID-19. Though cases in the U.S. are at their lowest point in a year, infections and hospitalizations have begun to climb again across Europe amid relaxed mitigation measures and the spread of a `` subvariant '' of omicron. Cases are rising sharply in China and Hong Kong, while potential warning signs have been observed in wastewater samples in the U.S.
So far, Congress has resisted authorizing billions of dollars in new emergency funding for COVID-19 treatments, tests and vaccines — something the Biden administration on Tuesday warned could have `` severe consequences '' for the country's ability to deal with any future surge.
`` Waiting to provide funding once we're in a surge will be too late, '' the White House said in a statement. A lack of funding could compromise the government's ability to make additional boosters — or, if necessary, variant-specific shots — available to all people in the U.S., the administration added.
Pfizer CEO Albert Bourla, in multiple recent media appearances, has said an additional dose would be `` necessary. '' Still, the company is only seeking authorization of a second booster for the elderly, who are most vulnerable to severe illness. The fourth shot would be for people who have been previously boosted with any vaccine, the company said.
Moderna, meanwhile, is currently studying both an omicron-specific shot and a two-pronged vaccine tailored to the variant as well as the original coronavirus strain.
Topics covered: Pharma, biotech, FDA, gene therapy, clinical trials, drug pricing and much more.
More than one quarter of the medcines cleared by the FDA's main review office since 2015 have been cancer drugs, a tally that reflects the advent of cancer immunotherapy as well as continued progress in matching treatment to genetics.
After several family members had early heart attacks, Kathiresan vowed to understand why they happen. His research journey has changed medical practice and led to a new biotech startup, Verve Therapeutics, that seeks to prevent them.
Topics covered: Pharma, biotech, FDA, gene therapy, clinical trials, drug pricing and much more.
Topics covered: Pharma, biotech, FDA, gene therapy, clinical trials, drug pricing and much more.
More than one quarter of the medcines cleared by the FDA's main review office since 2015 have been cancer drugs, a tally that reflects the advent of cancer immunotherapy as well as continued progress in matching treatment to genetics.
After several family members had early heart attacks, Kathiresan vowed to understand why they happen. His research journey has changed medical practice and led to a new biotech startup, Verve Therapeutics, that seeks to prevent them.
Topics covered: Pharma, biotech, FDA, gene therapy, clinical trials, drug pricing and much more. | tech |
KENYA: KeNHA puts it foot down on Kenol-Marua highway | Chinese firms grouped under Hass Consortium-GVR Infra, a company created to meet the upgrade needs of stretches of highways in northeast Kenya, hope to obtain approval of a $ 154.2m guarantee from the Multilateral Investment Guarantee Agency ( MIGA) so that work can finally begin. [... ]
Supported by international donors, Kenyan authorities are trying to end the isolation of the country's northeast region, which is a key to connecting the Horn of Africa's various economies. [... ]
The Kenya National Highways Agency ( Kenha) has at last launched the call for tenders for the Makupa Bridge project first announced by the local authorities in 2017. [... ]
The start of work on the new pedestrian bridge over the Likoni Channel, which the authorities say is imminent, moved a step closer with the acquisition by the Kenyan government in early July of land bordering on the construction area. [... ]
The renewable energy producer Ergon Solar drew on the contacts of its vice president Alberto Soprani among Kenya's presidential clan to push forward with its solar power plant in Kenya. [... ]
Despite the Covid-19 pandemic, which has grounded aircraft all around the world, Yaoundé is actively seeking a consultancy firm to help it to develop the country's civil aviation industry. [... ]
The Nairobi-Nakuru-Mau Summit highway project, overseen by the Kenya National [... ]
The country's roads agency has begun the process of recruiting a consultant to plan and supervise the construction of two legs of the road between Kenya and Tanzania. [... ]
The nine companies competing for the contract must submit their bids before the end of January. [... ]
The Kenya National Highway Authority ( KeNHA) is getting down to [... ]
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KENYA: Egis wins Kenyatta over on Nairobi Railway City project | The Egyptian construction firm Wadi El Nile is the favourite to win the tender call for the redesign of the station district of the Kenyan capital, estimated to be worth in the region of $ 255m. [... ]
The next East African Business Council conference is likely to see Kenya quizzed on its solo trade talks with the UK. [... ]
China has suspended work to extend its Mombasa-Nairobi railway line to Uganda to protest over the plans of US firm Bechtel to build a motorway between the port and the capital. [... ]
The proposed permit extensions for two blocks in Turkana have not gone down well with the French major and it is now threatening to pull out altogether. Here's why. [... ]
Kenyan president Uhuru Kenyatta's late September visit to Paris will only be announced at the last minute to avoid any disappointment should Covid-19 thwart his plans. If he does make it, business should be the main item on the agenda. [... ]
Africa Intelligence uses cookies to provide reliable and secure features, measure and analyse website traffic and provide support to the website users.Apart from those essential for the proper operation of the website, you can choose which cookies you accept to have stored on your device.Either “ Accept and close ” to agree to all cookies or go to “ Manage cookies ” to review your options. You can change these settings at any time by going to our Cookie management page.
A cookie is a text file placed on the hard drive of your terminal ( computer, smart phone, tablet, etc.) by the website. It aims to make browsing more fluid and to offer you content and services tailored to your interests.
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A pioneer on the web since 1996, Africa Intelligence is the leading news site on Africa for professionals. | general |
COVID-19 Isn’ t Done with Us Yet, Vaccine Patents and a 4th Booster | For a brief time - again - the COVID-19 pandemic appeared to be fading. Now that Omicron is becoming less common, its sister variant, BA.2, seems to be surging worldwide and in the U.S. For that and more, continue reading.
The World Health Organization indicates that the next COVID-19 variant is more contagious than Omicron. However, the most important question is whether it will be more deadly, and nobody seems to know if that will be the case.
“ The next variant of concern will be more fit, and what we mean by that is it will be more transmissible because it will have to overtake what is currently circulating, ” said Maria Van Kerkhove, WHO’ s COVID-19 technical lead. “ The big question is whether or not future variants will be more or less severe. ”
She also warned against theories that the virus will become milder as it mutates. “ There is no guarantee of that, ” she said. “ We hope that that is the case, but there is no guarantee of that, and we can’ t bank on it. ” She is also concerned that newer variants may evade vaccine protection more.
CDC: Omicron BA.2 SubVariant Makes Up About 25% of New U.S. COVID-19 Cases
The so-called “ stealth ” variant, BA.2, a sister variant to Omicron BA.1, is surging worldwide. The U.S. Centers for Disease Control and Prevention estimated that BA.2 now makes up almost a quarter of new COVID-19 cases in the U.S., an increase from around 10 or 11% last week. The prevalence of BA.2 is highest in the Northeast, mainly from New York and New Jersey, where it appears to make up about 39.0% of circulating viruses, and in New England, about 38.6%. BA.2 is spiking in China and Europe. Generally, although BA.2 is surging, it currently seems as if hospitalizations and deaths are not surging in parallel, although those often trail infections by two weeks. However, hospitalizations and deaths may be lower because a large percentage of the population has immunity caused by vaccination and previous infections.
The World Trade Organization ( WTO) has reportedly brokered a deal with the U.S., EU, India and South Africa over intellectual property ( IP) waiver over patents on COVID-19 vaccines. The agreement would allow for inexpensive generic versions of some vaccines to be manufactured and distributed to poorer countries more quickly.
The WTO has been trying to find common ground on the deal for about 18 months. The new agreement differs significantly from the initial proposal first introduced by India and South Africa in October 2020. That proposal wanted to suspend patents for successful vaccines, treatments and diagnostics, such as those by Pfizer-BioNTech and Moderna for the entire pandemic.
The new agreement will still need everybody in the WTO and the four global powers to sign off, but if that happens, the patents for COVID-19 vaccines will be suspended for three or five years, but IP patents will still protect the treatment and testing formulas. It would only apply to developing WTO countries that export less than 10% of world exports of COVID-19 vaccine doses in 2021. The deal also does not apply to technology transfer and trade secrets.
As COVID-19 surges in China, the country locked down major swaths, including ports, vehicle and electronics factories. One of the major areas shut down was Shenzhen, a technology and finance hub adjacent to Hong Kong, and Changchun, an automobile center.
“ We can think of no risk to the global economy, excluding nuclear warfare, that is greater than the risk of a COVID outbreak in China that shutters industrial production, ” said Carl B. Weinberg of High-Frequency Economics in a report. “ Uncountable manufacturing supply chains pass through China. ”
Pfizer-BioNTech filed for an emergency use authorization ( EUA) with the U.S. Food and Drug Administration for the fourth shot of their COVID-19 vaccine for people 65 years and older. The argument is the shot is necessary to boost waning immunity. It is based on real-world data collected in Israel.
The FDA also plans to hold an advisory committee meeting in early April to review whether there should be a program in October or November to encourage some or all adults to get another booster, perhaps along with the annual influenza vaccine campaign. It’ s not clear if an advisory committee meeting will be necessary to discuss the EUA. But the adcom will discuss whether additional shots should be the same version currently available or modified to target new variants.
Senior White House officials indicated the federal government doesn’ t have money in the budget to pay for a fourth shot after last week’ s $ 16.5 billion proposal to fund vaccines and other coronavirus programs was shot down. The original request was for $ 22.5 billion for supplemental COVIDI-19 aid. But the aid was culled from the fiscal 2022 omnibus spending measure over a disagreement over the source of the money. The cuts will also make it more difficult for the uninsured to access COVID-19 resources.
“ Testing capacity … will decline this month, ” said White House press secretary Jen Psaki during a briefing last week. “ In April, free testing and treatments for tens of millions of Americans without health insurance will end. In May, America’ s supply of monoclonal antibodies will run out. ”
Although earlier data suggested the Johnson & Johnson one-shot COVID-19 vaccine was not as effective as the Pfizer-BioNTech and Moderna vaccines, new data suggests it is roughly equivalent to preventing infections, hospitalizations and deaths. The New York Times reports that the reasons for this aren’ t clear, and there is no agreement among experts, but accumulated data suggests the J & J vaccine is similarly effective to its competitors. | general |
Novartis, Lilly, Merck and More Halt Business Operations in Russia | More and more pharmaceutical companies are joining in the effort to put economic pressure on Russia by suspending some or all operations within that country following the invasion of Ukraine.
One day after Pfizer announced it was halting its business practices within Russia, AbbVie, Abbott, Novartis, Merck and Eli Lilly have followed suit. This morning, Merck announced plans to halt all investments made in Russia in protest of the invasion. Like Pfizer and other companies, the pharma giant would continue to supply life-saving medications in support of ongoing humanitarian efforts. According to Reuters, which was the first to report Merck’ s decision, the company noted that it sent 135,000 courses of its antiviral COVID-19 pill, molnupiravir, to Ukraine under a supply agreement previously struck with that government. There are increasing concerns of an outbreak of the virus in Ukraine due to the close proximity of people sheltering in bunkers to avoid Russian artillery.
Indianapolis-based Eli Lilly announced it was suspending sales of “ non-essential medicines ” within Russia, according to Reuters. The company, however, will continue to send drugs developed for cancer and diabetes to the country. Additionally, Lilly is suspending all investments within Russia and will not begin any new clinical programs in the country.
“ We also have suspended all investments, promotional activities, and new clinical trials in Russia, as well as the exportation of non-essential medicines to that country. Our Russian operations are now only focused on ensuring people suffering from diseases like cancer and diabetes continue to get the Lilly medicines they need. Should we generate any profits from our sales in Russia, we will donate them to organizations dedicated to humanitarian relief, ” Eli Lilly said in a statement on its website.
Novartis halted investments and marketing activities within Russia. Also, the Swiss pharma giant ceased “ all scientific events organized by the company or external parties in Russia, ” Reuters said.
Johnson & Johnson has halted enrollment of clinical programs, while Illinois-based AbbVie has halted operations for its aesthetics business in Russia, which includes the blockbuster treatment Botox.
Bayer and Abbott have also halted business operations. In a statement issued Tuesday, life sciences giant Bayer said it will halt all non-essential business in Russia and Belarus “ while ensuring continued access to health and agriculture products. ”
“ As a response to Russia’ s invasion of Ukraine, Bayer stopped all spending in Russia and Belarus that is not related to supplying essential products in health and agriculture. This includes suspending all advertising and other promotional activities, halting capital investment projects indefinitely and not pursuing any new business opportunities, ” the company said in a statement. | general |
Outsourcing the backend of the supply chain begins with 3PL | If there’ s one thing that’ s become clear, it is that the COVID-19 crisis has put the supply chain in the spotlight.
The importance of investing in a resilient supply chain has never been more important, especially when it comes to disrupted workforces and the importance of delivering goods in a digital-first world.
“ With everyone working from home, B2B deliveries are beginning to look a lot more like B2C deliveries, ” explains Tim Proome, Tarsus Distribution’ s Head of Supply Chain. “ This adds increased complexity to the last mile owing to the fact that a delivery into a residential complex has a very different rhythm to that of a business location. ”
One of the biggest struggles facing businesses today is being able to keep up with supply chain challenges, especially in areas like shipping, warehousing and logistics. The dynamics around supply chains are constantly changing and executing the last mile isn’ t as simple as getting an item from point A to point B as quickly as possible.
While faster order fulfilment is the new norm, businesses are having to reconsider how they get to customers: “ The type of truck going into a B2B environment may not be allowed to go into a complex. Now suddenly, you’ ve got the wrong vehicles going into the wrong areas, ” says Proome.
In a B2C world, digital integration platforms are often about survival and without the right management systems in place, organisations risk losing out to competitors if they can not deliver goods accurately, timeously, cost-effectively and with real-time visibility.
“ A good warehouse management system is critical. We worked with an e-commerce customer who took six months to deliver their Black Friday deals. We did their digital integration and when their Black Friday sale happened the following year, it doubled in volume but we were able to execute in a week, ” adds Proome. “ Being able to scale from 4 000 transactions in a month to 8 000 transactions in a weekend is only possible because the system is all digital and that makes the supply chain more flexible. ”
The B2C shift has also impacted the visibility of business orders. Ordering from an e-commerce store, a customer is able to track a delivery from the warehouse to his house but in a business environment, this is not always the case. “ It should be fully-integrated and fully visible, ” says Proome. “ You should be getting the same experience of a B2C or e-commerce environment in B2B - digital visibility is far more important than a physical warehouse because the supply chain is what makes or breaks customer relationships. You can have a warehouse sitting right next to you but if you don’ t have the right systems talking to each other, what’ s the point? ”
In the logistics environment, there are usually two ( possible) chargeable metrics - the actual weight of the product and the volumetric weight. Whichever is greater becomes the cost.
“ From a cost perspective, companies are at the mercy of couriers but within a smart warehouse, there’ s not only video footage, the data captured about the item contains all the necessary data and as a result, those cost queries go away, ” says Proome. “ In those economies of scale, it is easy to get bogged down by tonnes of operational exceptions where your core competency is probably marketing and selling your product. If you started an e-commerce website and began dispatching items out of your double garage, you would spend a lot of time dealing with customers and less time dispatching - something is always going to get sacrificed along the way. ”
However, when a business outsources e-commerce logistic processes to a third-party business, those exceptions can become minimised. An experienced third-party logistics ( or 3PL) supplier should be able to fulfil orders accurately and with full visibility, no matter the size of the business.
“ A small customer that comes into an 3PL warehouse environment can get the same, speed-to-serve as a large corporate, ” adds Proome. “ A good warehousing management system is extremely expensive to implement, optimise and maintain and the outcome may be that after spending months implementing you only achieve parity with the market in terms of operational excellence. ”
The e-commerce sector grew by 33% in 2021 which means there is an increased demand for logistics services. For Proome, he sees the future of the supply chain shifting into an ‘ as-a-service’ model. “ Services are becoming the big selling ticket as opposed to product. If everything in the backend supply chain changes to an as-a-service model, 3PL service providers will help businesses to scale more effectively while consolidating more shipments going forward. ” | general |
Hybrid work turns spotlight on need for advanced asset management | The COVID-19 pandemic and the resulting move to hybrid work models turned asset management into a top priority for South African businesses virtually overnight.
This is according to Jonathan Bass, Managing Director of enterprise asset management specialist NetTrace ( Pty) Ltd, whose solution portfolio includes asset tracking, risk management, security and reporting tools for all enterprise assets.
Bass says NetTrace’ s solutions, born out of IT asset loss control technology over 20 years ago, are now in high demand as organisations realise how crucial it is to maintain accurate asset registers, and track leased and owned assets throughout the asset lifecycle.
“ When the environment became more complex due to remote and hybrid work, organisations realised asset management and security had become a bigger problem – they needed to manage devices remotely and roll out security policies to remote devices. To meet these needs, we also offer endpoint security and are about to launch a VPN management toolset, ” he says.
Gift Mkhonza, Business Development Manager for NetTrace at Axiz, says a key procurement challenge organisations now face is a disparate, fragmented system that lacks the integration required for end-to-end visibility. “ The challenge in the South African region is a lack of visibility of the usage and lifespan of managed assets. If an organisation does not have an accurate asset baseline to work from, it can not expect to manage a return on investment on assets, whether these are physical or software-based, ” he says. “ Many organisations can not be sure they’ re managing all assets. When asset-based decisions are driven by data that is inaccurate, outdated, or incomplete, there could be numerous unwanted implications for the business. ”
Bass elaborates: “ The issue is that while most organisations have fairly well-structured processes for purchasing assets, procurement is not where the problem lies. The problem starts when the asset goes into the production or working environment. At that point, you need to ensure what you think you purchased is actually what you purchased, if there are discrepancies, there will be a problem with your audits in future. Then, it’ s about deployment of the asset in its operational state – ensuring it is assigned to the right department or person, and that the organisation gets a return out of that procurement. “
NetTrace solutions integrate management and reporting across the complete operational spectrum; plan, acquire, deploy, manage and retire phases of asset management. The technology goes further to enable more efficient auditing via the NAMScan App or via its Tracking Agents and automation, and track and secure endpoint devices with Canadian-based Absolute Software technology. Bass notes: “ We automate into registers, stores management and the verification of assets and generate business information about the asset environment.
Says Mkhonza: “ Analytics are a crucial, if not the most important aspect of any business. Often companies spend a fortune employing a business analyst or external consultancy to manage the health of their business; however, with NetTrace you have access to a console that is so easy to analyse and manoeuvre, it will turn anyone into a business analyst/decision-maker as it gives you a holistic asset tracking, risk management and reporting in a single pane of glass. ”
Opportunities in asset management support services
While advanced asset management is now accessible to any enterprise, skills shortages can still make optimisation of these systems a challenge. Bass says. “ The solutions exist, but often the problem is in the implementation and support. NetTrace sees huge opportunities for resellers to offer support services in South Africa. ”
Mkhonza says: “ Support services are a vital part of the market, especially when it involves hardware investments. In the multi-faceted managed services world, support services are becoming a powerful way for channel resellers to build stronger relationships with their customers and discover upsell opportunities.
Support services help businesses with a number of challenges, like helping organisations to identify and adapt to new technologies that will assist them to grow, as well as ensure smooth business continuity during procurement and implementation. ”
As a leading digital technologies and services distributor providing world-class products and a host of services, Axiz has built commercial and technological ecosystems that allow its partner base to provide best-of-breed solutions that meet the business needs of its customers, Mkhonza says. “ We believe that NetTrace fits very well in this strategy, as they give our channel partners the ability to meet surging demand for solutions that dynamically monitor asset environments and deliver real-time information for decision-making. There are also opportunities to add value with service and support over and above the actual technology, ” he says. | general |
SNP calls for cross-sector windfall tax | The SNP has called for a broad-based windfall tax on ‘ excess profits’ of major companies, including the energy sector, to help ease the cost of living crisis.
In an Opposition Day motion scheduled for Wednesday March 16, the party will lead a debate calling on the UK Government to scrap VAT on energy bills, and to implement a windfall tax on companies which are benefiting from “ significantly increased profits ” as a result of the pandemic or the current international disruption caused by Russia’ s invasion of Ukraine.
The broad-based windfall tax is aimed at Amazon and other large retailers, as well as energy companies, according to the SNP’ s Business, Energy and Industrial Strategy spokesperson Stephen Flynn MP.
Mr Flynn said this would ensure that all major companies who have made excessive profits during the Covid pandemic and energy crisis can now “ shoulder the burden ” faced by millions of families.
The motion also demands the scrappage of the energy bill rebate scheme.
The measures would fund a “ comprehensive package of support ” for families, including emergency cash payments for households, to tackle the rising cost of living, the party said.
It cited Institute of Fiscal Studies analysis that suggests households are on course to be £800 worse off this year as a result of spiralling costs.
The debate comes just one week before the government’ s spring budget. Mr Flynn said it was “ absolutely essential that the Chancellor stops making excuses and delivers a comprehensive package of support without further delay. ”
He added: “ Other countries across Europe are already taking meaningful action to support people. It’ s time the UK government finally caught up with our European neighbours and used the reserved powers it stubbornly refuses to devolve to Scotland.
“ The SNP is calling for a broad-based windfall tax on all major companies that have made excessive profits during the pandemic and energy crisis. It is only right that companies making these huge profits shoulder the burden that families face.
“ This must be a balanced approach across companies, which recognises investment in communities, rather than the ill-considered smash-and-grab on the north east of Scotland proposed by others. ”
A potential windfall tax on North Sea oil companies has also been mooted by Labour and by campaigners in the wake of the record profits reported across the sector. | general |
Nazanin Zaghari-Ratcliffe 'on way home ' to UK after 6 years ' detention in Iran, British lawmaker says |
Nazanin Zaghari-Ratcliffe
, the British-Iranian charity worker who has been held in
Iran
for almost six years, has been released and is en route back to the UK.
On Wednesday, Zaghari-Ratcliffe's local UK Member of Parliament Tulip Siddiq tweeted a photo of her on board a plane saying she is now on her way home.
`` It's been 6 long years - and I can't believe I can FINALLY share this photo, '' wrote Siddiq. `` Nazanin is now in the air flying away from 6 years of hell in Iran. ''
UK Foreign Secretary Liz Truss said in a tweet that Zaghari-Ratcliffe and fellow British Iranian national Anoosheh Ashoori `` will be reunited with their families later today. ''
UK Prime Minister Boris Johnson hailed their release as `` huge achievements '' for British diplomacy. `` I pay tribute to the tireless efforts of those who have worked for six years to make today's events possible, '' Johnson wrote in a tweet.
Read More
This comes as Truss announced that the UK had settled a decades-old £400 million ( $ 524 million) debt owed to Iran, which Iran's Foreign Minister Hossein Amir-Abdollahian denied was linked to the prisoner release.
`` After highly complex and exhaustive negotiations, the more than 40-year-old debt between the International Military Services and the Ministry of Defense of Iran has now been settled, '' Truss said in statement to Parliament.
The debt is for undelivered armored vehicles and tanks, originally ordered by Iran but canceled by the UK in response to the Iranian revolution of 1979, according to a research briefing published by the House of Commons Library.
How the Ukraine war revealed Europe's selective empathy on refugees
Iran's state-run Press TV said that Zaghari-Ratcliffe had been handed over to the UK government, without providing any further details. The country's semi-official Fars news agency said she was being transferred to Tehran's international airport, Imam Khomenei, with a British negotiating team.
On Wednesday, Hojjat Kermani, Zaghari-Ratcliffe's lawyer, told CNN he did not want to comment on the latest developments for now.
He earlier told Reuters that Zaghari-Ratcliffe and another detained British-Iranian, Anousheh Ashouri, were `` on their way to the airport in Tehran to leave Iran. ''
Mayor of London Sadiq Khan said he was `` delighted '' that Zaghari-Ratcliffe had been freed from `` wrongful imprisonment '' in a statement Wednesday.
`` Nazanin and her loved ones have shown great courage, strength and steadfastness during what has been an unimaginably difficult time, and I want to pay tribute to all those who have campaigned tirelessly for her release, '' said Khan. `` London looks forward to welcoming her home. ''
Her husband Richard Ratcliffe said the release of his wife means they can `` start being a normal family again. ''
Speaking to reporters in London, Ratcliffe said he hadn't yet spoken to his wife but that they had exchanged messages on Wednesday.
He said she got picked up by the Iranian Revolutionary Guard at 11:00 a.m. local time ( 3:30 a.m ET) and that although she `` wasn't really allowed to speak '' he was aware of her movements.
`` Her homecoming is a journey not an arrival. There will be a whole process and hopefully we will look back in years to come and we will be a normal family, '' Ratcliffe continued.
On Wednesday, a campaign group which pushed for Zaghari-Ratcliffe's release thanked Siddiq, the family's member of parliament, for her work on the case.
`` You have made a difference @ TulipSiddiq! Thanks for all the amazing support you have given to # FreeNazanin over these 6 long years, '' the group wrote on Twitter.
Nazanin Zaghari-Ratcliffe was first detained at a Tehran airport in April 2016 following a vacation to see her family with her daughter.
Husband's hunger strikes
Zaghari-Ratcliffe was first detained at a Tehran airport in April 2016 following a vacation to see her family with her daughter.
She was accused of working with organizations allegedly attempting to overthrow the Iranian regime and was later convicted and sentenced to five years in jail.
Zaghari-Ratcliffe and her employer, the Thomson Reuters Foundation, have repeatedly denied the espionage charges against her.
In April 2021 she was handed a second jail sentence and travel ban on charges of spreading propaganda against the regime, and lost an appeal on her case in October.
Zaghari-Ratcliffe was given British diplomatic protection in 2019 and was designated a prisoner of conscience by Amnesty International.
She undertook at least three hunger strikes during her detention, one of them in a desperate bid to seek medical treatment for lumps in her breasts and numbness in her limbs.
Her husband Richard Ratcliffe has also carried out hunger strikes in solidarity with his wife.
The couple's daughter, Gabriella, who was just 22 months old at the time of her mother's arrest, is now almost eight.
In 2019, Zaghari-Ratcliffe's supporters said she was transferred to the mental ward of a hospital in Tehran and was being denied visits from her father.
In February 2020, Zaghari-Ratcliffe's family said she believed she had contracted Covid-19 in Evin Prison outside Tehran.
CNN's Hamdi Alkhshali, Vasco Cotovio, Nada Bashir, Sarra Alayyan, Zeena Saifi and Lauren Said-Moorhouse contributed to this report. | general |
FC Barcelona and Spotify sign multi-year shirt and stadium sponsorship deal |
FC Barcelona
has signed a multi-year shirt and stadium sponsorship deal with audio streaming platform Spotify, the Spanish club announced Tuesday.
For the very first time in the club's history, Barcelona's iconic stadium will be rebranded as the Spotify Camp Nou.
The brand will also appear on the front of the men's and women's team shirts for four seasons from the 2022-23 campaign.
Rakuten, an online shopping company, has sponsored the men's team since 2017, while tools and storage company Stanley Black & Decker became the official shirt sponsor of the women's team in 2018.
Up until 2006, when it agreed a deal with UNICEF, Barcelona shirts were iconic for not featuring any sponsors.
Read More
`` The partnership [... ] is a first-of-its-kind for the club in bringing the worlds of music and football together, giving a global stage to players and artists [... ] and building new opportunities to connect artists and players with fans around the world, '' the club said in a statement.
The agreement is now subject to ratification at the Extraordinary Delegate Members Assembly that's due to take place on April 3.
Neither Barcelona nor Spotify confirmed the financial details of the deal.
Barcelona is looking to usher in a new era at the club.
Years of financial mismanagement has forced Barça to cut loose many of its most valuable assets -- including former captain Lionel Messi, the greatest player in the club's history.
Last year, President Joan Laporta revealed the
full extent
of the club's `` very worrying '' situation, stating that Barcelona were over $ 1.5 billion in debt with a negative net worth of $ 515 million.
The club will hope the new deal can help kickstart a new era for the club as it looks to rebuild its young squad.
Barcelona is currently third in La Liga and is starting to improve after a terrible start to the season.
Last year, Spotify founder Daniel Ek expressed an interest in buying English Premier League side Arsenal, but the current owners did not want to sell.
The streaming service, which has built an empire of 172 million subscribers in 180 countries, also found itself in the middle of controversy this year over
podcaster Joe Rogan
.
Artists such as Neil Young and Joni Mitchell asked Spotify to pull their music from the platform because Rogan had made frequent false and inaccurate claims about Covid-19 and vaccines on his very popular podcast, `` The Joe Rogan Experience. ''
Following the backlash, Spotify said it would add a content advisory to any podcast episode that includes discussion about Covid-19. | general |
Rate hikes are here: What does that mean for you? |
The Covid era of free money has come to an end.
After dropping interest rates
to zero in March 2020
to revive the economy, the Federal Reserve has just
shifted gears to go into inflation-fighting mode.
Fed officials said Wednesday they are raising interest rates, beginning their first cycle of rate hikes since the one that began in late 2015.
The fact that the Fed is finally moving away from zero shows confidence in the health of the jobs market. But the speed with which interest rates could go up underscores concerns about the soaring cost of living.
High inflation -- consumer prices rose in February at the
fastest pace in 40 years
-- means the Fed will raise interest rates multiple times in the coming months, central bank officials confirmed on Wednesday.
Read More
Americans will experience this policy shift through higher borrowing costs: No longer will it be insanely cheap to take out mortgages or car loans. And cash sitting in bank accounts will finally earn something, albeit not much.
`` Money will no longer be free, '' said Joe Brusuelas, chief economist at RSM US.
Oil briefly tumbles below $ 100 a barrel. That's good news for gas prices
When the pandemic erupted, the Fed made it almost free to borrow in a bid to encourage spending by households and businesses. To further boost the Covid-ravaged economy, the US central bank also printed trillions of dollars through a program known as quantitative easing. And when credit markets froze in March 2020, the Fed rolled out emergency credit facilities to avoid a financial meltdown.
The Fed's rescue worked. There was no Covid financial crisis. Vaccines and massive spending from Congress paved the way for a rapid recovery. But now the Fed must take on another challenge: rising inflation. Here's how higher rates will impact consumers.
Borrowing costs are going up
Today,
unemployment is very low
but
inflation is very high
. The US economy no longer needs all that help from the Fed.
Every time the Fed raises rates, it becomes more expensive to borrow. That means higher interest costs for mortgages, home equity lines of credit, credit cards, student debt and car loans. Business loans will also get pricier, for businesses large and small.
The most tangible way this is playing out is in mortgages, where expectations of rate hikes have already driven up rates.
Key inflation measure hits double digits for February
The rate for a 30-year fixed rate mortgage
averaged 3.85% in the week ending March 10
. While that's still cheap historically, it's up sharply from under 3% in November.
Higher mortgage rates will make it harder to afford home prices that have
skyrocketed during Covid
. But weaker demand could cool off prices. The median price for an existing home sold in January soared by 15.4% year-over-year to $ 350,300
.
But it 'll still be relatively cheap to borrow
None of this means it will suddenly become expensive to finance purchases.
Federal Reserve Chairman Jerome Powell said the central bank will likely raise interest rates six more times this year, for a median federal funds rate of 1.9% by the end of the year.
While that's up from 0.125% today, it's still low historically.
For context, the Fed raised rates to as
high as 2.37%
during the peak of the last rate hiking cycle in late 2018. Before the Great Recession of 2007-2009, Fed rates got as high as 5.25%.
And in the 1980s, the Paul Volcker-led Fed jacked interest rates up to unprecedented levels to
fight runaway inflation
. By the peak in July 1981, the effective fed funds rate topped 22%. ( Borrowing costs now won't be anywhere near those levels and there is little expectation that they will go up that sharply.)
Still, the impact to borrowing costs in coming months will depend chiefly on the speed of the Fed's rate hikes. There remains much debate about that, although Chairman Jerome Powell said in January he believes there is `` quite a bit of room '' to raise rates without threatening the jobs market.
Good news for savers
Rock-bottom rates have penalized savers.
Money stashed in savings, certificates of deposit ( CD) and money market accounts has earned almost nothing during Covid ( and for much of the past 14 years, for that matter). Measured against inflation, savers have lost money.
The good news, however, is that these interest rates will rise as the Fed gets away from zero. Savers will start to earn interest again.
But this takes time to play out. In many cases, especially with traditional accounts at big banks, the impact won't happen be felt overnight.
And even after several rate hikes, savings rates will still be very low -- below inflation and expected returns in the stock market.
Markets will have to adjust
Free money from the Fed has been amazing for the stock market.
Zero percent interest rates depress government bond rates, essentially forcing investors to bet on risky assets like stocks. ( Wall Street even has an expression for this: TINA, which stands for `` there is no alternative. '')
War has brought the world to the brink of a food crisis
Higher rates could be a challenge for the stock market, too, which has become accustomed to -- if not addicted to -- easy money. Markets have already
experienced significant volatilit
y amid concerns about the Fed's plan to fight inflation. Last week, the
Nasdaq tumbled into a bear market
, signaling a 20% decline from previous highs.
But much will
depend
on how fast the Fed does raise
interest rates
-- and how the underlying economy and corporate profits perform after they do.
At a minimum, rate hikes mean the stock market will face more competition going forward from boring government bonds.
Cooler inflation?
The goal of the Fed's interest rate hikes is to get inflation under control, while keeping the jobs market recovery intact.
Consumer prices spiked by 7.9% in February from the year before, the fastest pace since January 1982. Inflation is nowhere near the Fed's goal of 2% and has gotten worse in recent months.
Economists warn inflation could get even worse in March because commodity prices have spiked since Russia's invasion of Ukraine. Everything from
food
and
energy
to metals have become more expensive, although oil prices have pulled back from their recent highs.
And in recent days, China has
suffered its worst Covid-19 outbreak
in two years, prompting authorities to
lock down key parts of the country
. The lockdowns will add
further pressure to scrambled supply chains
at the heart of inflation.
The high cost of living is causing financial headaches for millions of Americans and contributing significantly to the decade low in consumer sentiment, not to mention President Joe Biden's low approval ratings.
Yet it will take time for the Fed's interest rate hikes to start chipping away at inflation. And even then, inflation will still be subject to developments in the war in Ukraine, the supply chain mess and, of course, Covid. | general |
Solana, Terra, & Bitcoin- Top Cryptocurrencies to Keep on Watchlist for 2022 | These AI stocks are loved by millionaires. If you want
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The cryptocurrency market has been volatile in March 2022. The aftermath of President Biden’ s executive order on cryptocurrencies saw the market gain $ 120 billion overnight. But as of March 10 the market has fallen back down to around $ 1.75 billion market cap.
All top 20 crypto tokens are down in price over the last 24 hours. However, with $ 1.7 trillion proving to be a key resistance level this year, now could be the perfect time to increase positions. Especially since the US’ new executive order on crypto recognised the need to support innovation in the industry.
CEO and co-founder of Circle – Jeremy Allaire – said the EO was a ‘ watershed moment’ for crypto and digital similar to the Internet in 1996/1997. While the Russia-Ukraine crisis, record-high inflation and effects of the COVID pandemic can still challenge the crypto market there’ s every chance of a rebound.
In this article we’ ll look at Bitcoin, EverGrow Coin, Polkadot, Solana and Terra LUNA.
Bitcoin surged on Wednesday, March 9, following President Biden’ s executive order. BTC reached a price of $ 24,000 yesterday but is now back under $ 40k once more. Bitcoin remains the largest and most influential cryptocurrency on the market, and it’ s dominance is unlikely to change anytime soon. Bitcoin’ s market cap is still at least $ 400 billion above the competition.
EverGrow Coin is the smallest crypto in this last by market cap, but it’ s also the youngest. EverGrow Coin is about to release the first of a suite of game-changing apps – it’ s a content subscription platform called Crator that accepts crypto payments. Crator will charge just 5% commission on payments for different subscription tiers and livestream videos, compared to OnlyFans’ 20% commission and long waiting period for withdrawals. EverGrow Coin is also a rewards token that will see BUSD reflections for investors directly from the profits of applications like Crator and even before utilities lauch evergrow has already distributed more than $ 35,000,000 BUSD in rewards.
President Biden’ s executive order underlined the need to prevent climate risks in crypto. Bitcoin is well known as a power-hungry protocol, due to its consensus mechanism called proof of work ( PoW). The main rival to PoW is a mechanism called proof of stake ( PoS), and a recent study from the Crypto Carbon Ratings Institute found Polkadot had the lowest total electricity consumption and total carbon emissions per year ( out of six of the biggest PoS projects) in the crypto space.
Solana is the 9th biggest cryptocurrency by market cap, and challenges Bitcoin on another front: transactions per second ( TPS). Bitcoin can process around 10 transactions per second. This is far slower than Solana, found to have a TPS of 50,000 according to a recent Zycrypto report. Solana’ s speed could prove in its favour should cryptocurrencies enjoy wider appeal in 2022.
LUNA is the native token of the Terra blockchain ecosystem. LUNA is down in the last 24 hours but showing the least losses of major crypto – 0.06%. LUNA’ s price has been rocketing up this year and at the beginning of March was showing over 80% price increase in the previous seven days.
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France unveils'resilience plan ' to cushion impact of Russia sanctions | `` We have to prepare for a long crisis, '' Prime Minister Jean Castex told a news conference as he presented the new `` resilience plan '' on Wednesday.
`` We must prepare without delay measures to limit the impact on our companies, our jobs and our purchasing power '', he said.
With presidential elections less than a month away, the government already last year capped gas and power price increases and offered financial handouts to low-income households to cope with higher energy prices and inflation.
As the Ukraine crisis puts additional pressure on prices, Finance Minister Bruno Le Maire said that the additional measures would bring the total bill to €25-26 billion.
Among the new measures, Castex said the government would cover more than half of the cost of companies’ increase in their gas and power bills to help absorb losses they would have otherwise suffered.
Meanwhile, firms struggling with high energy prices or the loss of export markets would be able to get tax and payroll charges postponed.
Castex said that the government would also prolong and expand state-guaranteed loans set up during the Covid-19 crisis as well as reactivate a subsidised furlough scheme for firms suffering from a drop in client demand.
Gas and oil prices soar to all-time highs amid Russian supply fears | general |
Europe urged to improve refugee plan as Ukraine war stokes pandemic | Conditions of war are known breeding grounds for viruses and bacteria – an invisible enemy – with limited access to clean water propelling the spread of disease among crowded populations of desperate people.
In a comment piece published in The Lancet, researchers warned that increased support was needed for countries on the front lines of the Ukraine conflict, like Poland, Slovakia, Bulgaria and the Czech Republic, who are feeling the strain of mass arrivals from their neighbours.
They called on `` all '' European countries to adopt “ evidence-based approaches ” that would properly respond to the health needs of displaced Ukrainians suffering a multitude of illnesses.
The refugees – mostly women and children – fear Russian shelling far more than the threat of Covid-19 and other communicable illnesses, including a resurgence of polio.
In its emergency response, Médecins Sans Frontières ( Doctors Without Borders) has been working to provide people with basic needs by handing out trauma kits and training medical staff both in Ukraine, in neighbouring countries, and at border crossing points.
Of the roughly 2.8 million people the UN says have fled Ukraine since Russia’ s invasion, some 13,900 have arrived in France – with thousands more on the way.
Food, clothes, accommodation and other donations are being funnelled through a centralised government platform.
Marlène Schiappa, the Minister Delegate in charge of Citizenship, has lauded the effort, and said that everyone from ordinary people to elected officials and businesses had joined in.
Meanwhile, the World Health Organization has warned the war in Ukraine, where about 34 percent of people are vaccinated against Covid-19, risks accelerating the pandemic – especially as local hospitals run out of crucial medical supplies and people are forced into makeshift bunkers.
“ Certainly this pandemic is not taking a break despite the fact that we have this war, despite the fact that we have challenges and many countries are facing challenges right now, ” WHO epidemiologist Maria Van Kerkhove warned.
As well as a spike in cases in Europe, infectious disease experts say the war could also give rise to the emergence of new virus variants. | general |
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