Japan’s Kanagawa prefecture said it has found another vial of Moderna Inc’s COVID-19 vaccine suspected of containing a foreign substance and has put the rest of the lot on hold.
In a statement on Tuesday, prefectural authorities said a pharmacist found several black particles in one vial upon checking for foreign substances before the vaccine’s use.
Japan suspended the use of 1.63 million doses https://www.reuters.com/world/asia-pacific/japan-withdraws-16-mln-moderna-covid-19-vaccine-doses-over-contamination-nikkei-2021-08-25 of Moderna shots last week after being notified of contamination in some of the supply. Moderna and Spanish pharma company Rovi, which bottles Moderna vaccines, have said the cause could be a manufacturing issue, and European safety regulators have launched an investigation.
Moderna has said no safety or efficacy issues had been identified from the issue.
Kanagawa prefecture said the vaccine’s domestic distributor, Takeda Pharmaceutical Co Ltd , had collected the vial with the suspected contaminant, and that about 3,790 people had already received shots from the same lot.
More Moderna shots were temporarily halted in two regions of Japan this week for what appears to be a separate issue of bits of the vials’ rubber stopper breaking off https://www.reuters.com/world/asia-pacific/japan-health-minister-says-okinawa-vaccine-contaminants-likely-needle-stick-2021-08-31 when needles are incorrectly inserted.
A Texas law banning most abortions in the state took effect at midnight, but the Supreme Court has yet to act on an emergency appeal to put the law on hold.
If allowed to remain in force, the law would be the most dramatic restriction on abortion rights in the United States since the high court’s landmark Roe v. Wade decision legalized abortion across the country in 1973.
The Texas law, signed by Republican Gov. Greg Abbott in May, would prohibit abortions once a fetal heartbeat can be detected, usually around six weeks and before most women even know they’re pregnant.
Abortion providers who are asking the Supreme Court to step in said the law would rule out 85% of abortions in Texas and force many clinics to close. Planned Parenthood is among the abortion providers that have stopped scheduling abortions beyond six weeks from conception.
At least 12 other states have enacted bans on abortion early in pregnancy, but all have been blocked from going into effect.
What makes the Texas law different is its unusual enforcement scheme. Rather than have officials responsible for enforcing the law, private citizens are authorized to sue abortion providers and anyone involved in facilitating abortions. Among other situations, that would include anyone who drives a woman to a clinic to get an abortion. Under the law, anyone who successfully sues another person would be entitled to at least $10,000.
Abortion opponents who wrote the law also made it difficult to challenge the law in court, in part because it’s hard to know whom to sue.
Texas has long had some of the nation’s toughest abortion restrictions, including a sweeping law passed in 2013 that the Supreme Court eventually struck down but not before more than half of the state’s 40-plus abortion clinics closed.
Lawmakers also are moving forward in an ongoing special session in Texas with proposed new restrictions on medication abortion, a method using pills that accounts for roughly 40% of abortions in the U.S.
Novartis AG has reached a deal to provide its cholesterol-lowering medicine Leqvio to patients via the U.K.'s National Health Service, the Swiss pharmaceutical company said Wednesday.
Over the course of three years, around 300,000 patients should be treated with Leqvio (inclisiran), Novartis said. The patients targeted are those at high risk of having a second cardiovascular event.
The treatment is part of a population health-management approach and aims to reduce patients' long-term elevated LDL cholesterol, a key modifiable risk factor in cardiovascular disease, the company said.
The collaboration with the NHS follows final recommendation for Leqvio from the U.K.'s medicines regulator, NICE.
As the delta variant spreads through Florida, data published by the Centers for Disease Control and Prevention suggest this could be the most serious and deadly surge in COVID-19 infections since the beginning of the pandemic.
As cases ballooned in August, however, the Florida Department of Health changed the way it reported death data to the CDC, giving the appearance of a pandemic in decline, an analysis of Florida data by the Miami Herald and el Nuevo Herald found.
On Monday, Florida death data would have shown an average of 262 daily deaths reported to the CDC over the previous week had the health department used its former reporting system, the Herald analysis showed. Instead, the Monday update from Florida showed just 46 “new deaths” per day over the previous seven days.
Thedramatic difference is due to a small change in the fine print. Until three weeks ago, data collected by DOH and published on the CDC website counted deaths by the date they were recorded — a common method for producing daily stats used by most states. On Aug. 10, Florida switched its methodology and, along with just a handful of other states, began to tally new deaths by the date the person died.
If you chart deaths by Florida’s new method, based on date of death, it will generally appear — even during a spike like the present — that deaths are on a recent downslope. That’s because it takes time for deaths to be evaluated and death certificates processed. When those deaths finally are tallied, they are assigned to the actual date of death — creating a spike where there once existed a downslope and moving the downslope forward in time.
Shivani Patel, a social epidemiologist and assistant professor at Emory University called the move “extremely problematic,” especially since it came without warning or explanation during a rise in cases.
Patel said Florida death data now show an “artificial decline” in recent deaths and without an explanation or context, and “it would look like we are doing better than we are.”
The change came the day after the state health department’s official Twitter account posted a series of late-night tweets accusing the CDC of publishing incorrect numbers, but offering little explanation
“As a result of data discrepancies that have occurred, this week, FDOH worked quickly and efficiently with CDC to ensure accurate display of data on their website the same day,” DOH spokesperson Weesam Khoury told the Herald in a statement at the time. “To proactively ensure accurate data is consistently displayed, the Department will begin daily submission of a complete renewed set of case data to CDC, including retrospective COVID-19 cases.”
The health department did not acknowledge the subsequent change in the data structure or its abrupt onset, leaving the public scrambling for answers as more than a year’s worth of data changed from one day to the next.
“It shouldn’t be left to the public, to scientists, national policy makers or the media to guess as to what these numbers are,” Patel said. “We know from the beginning that dates matter and that they tell us different things.”
Jason Salemi, an epidemiologist at the University of South Florida who has been tracking the state’s COVID data, said reporting by date of death is better for long-term studies of the disease.
“Deaths by date of death curve is the most accurate you can get,” Salemi said. “You know exactly when people died, you know how to construct the curve and exactly when we were experiencing surges in terms of deaths.”
But Florida’s new data structure is less useful for understanding the pandemic in real time, he warned.
“When you have big surges in deaths, the deaths by date reported will always show an increase while deaths by date occurred will go down,” Salemi said.
“Someone could have died yesterday and we may not know about it for a week, or two weeks,” Salemi said. As a result, new death trends as reported by the Florida health department are significantly lower when data are first reported and don’t immediately reflect the actual number of people who died that day.
During surges of cases and deaths, averaging seven days of deaths by report date provides an important early indicator of how many people have recently died of the disease — a number that will eventually be reflected in the data by date of death, Salemi said.
Although deaths by date the person died are not currently reflecting record numbers, trends based on newly reported deaths are currently almost 31% higher than previous peaks in summer of 2020 and over the holidays, the Herald analysis showed. Of the record deaths reported to the CDC between Saturday and Monday, the Herald found that the vast majority of the 902 victims died within the past two weeks.
The Herald also found that during the last two surges the trend lines using date of death showed peaks 25% and 8% higher respectively than the corresponding peaks by report date.
‘STATISTICAL SLEIGHT OF HAND’
The Florida health department has made several, unannounced changes to its data methodology over the span of the pandemic, abruptly switching between including and disregarding non-resident deaths in its total counts, for example. Salemi said such frequent variations make it difficult to report numbers in a consistent and transparent manner that’s easily understood by the public.
Florida hasn’t always depended on the CDC to be the exclusive publishing house for its daily numbers. Until June 4, the department published its own data, available in daily PDF reports and also provided to view and download through an online dashboard.
The downloadable data sets on cases and deaths included the report date as well as the date a person died or got sick, allowing journalists and independent researchers to select the best metric for their purposes. The daily reports showed additional cases and deaths added from one day to the next.
In June, as case numbers droppedand vaccination rates continued to rise, the health department discontinued the dashboard and changed to a weekly report. The only near-daily data was submitted by the health department to the CDC and published on the CDC Trend Tracker website.
At first, the data on the CDC website was updated in a largely predictable manner, similar to the way that the DOH had reported daily changes throughout the pandemic. Then on Aug. 10, without warning or any explanation from the health department or the CDC, the data for nearly every day of the previous year changed. Neither agency immediately explained the changes.
The CDC eventually confirmed what experts had hypothesized after comparing the new data to previous reports — that the Florida Department of Health had begun to report deaths by date of death. The change was also reflected in data about new cases, which went from being counted by date of report to “the date of specimen collection, confirmed COVID-19 laboratory test result, or clinical diagnosis,” according to the CDC website. The case data show less of a dramatic shift than death data because case data are reported more quickly than deaths.
The CDC website listed Florida as one of just 12 jurisdictions — 11 states and New York City — reporting new deaths by date of death as of the end of August. The choice of how to report is determined by each jurisdiction, according to the website.
Florida’s weekly report, published on Fridays, also shows a decline in deaths in recent weeks even as the number of total dead across the state spikes.Last Friday, the DOH report showed 389 COVID-19 deaths for the previous week. But a comparison of cumulative deaths from the report the week before showed that 1,727 additional deaths were logged by the health department over that seven-day period. The DOH chart of deaths shows a decline over the past two weeks.
THE FLORIDA DEPARTMENT OF HEALTH
The DOH weekly report notes “death counts include individuals who meet a standardized national surveillance case definition” but includes no descriptions of how the health department presents the numbers.
“Due to inherent delays in deaths being reported to the [Health] Department, the previous 14 days may be incomplete and are updated over time,” said Khoury, the health department spokesperson, in an Aug. 30 statement to the Herald. “The Department reports deaths by date of death to the CDC upon notification to the Department.”
The Florida health department does not provide that explanation on its website or anywhere in its weekly reports.
In consultation with epidemiologists the Herald continued to report additional cases and deaths added to the total each day in daily updates rather than relying on the number of “new cases” and “new deaths” DOH data attribute to the previous day. However, data still appear inconsistent, as deaths backfill in large semi-weekly batches, rather than in all weekday updates.
“The CDC has started displaying the Department’s submitted retrospective file twice a week on Mondays and Thursdays, which updates previous day deaths that were subsequently reported to the Department,” Khoury explained for the first time in Monday’s statement. The difference can be an addition of eight deaths one day, and 901 the following day, as happened in the middle of last week.
Without context about how data are reported, when recent numbers are low due to reporting lags, “people will think there’s nothing going on,” said Mary Jo Trepka, an infectious disease epidemiologist and professor at Florida International University.
Economist Tim Harford, author of “The Data Detective,” who spoke generally about how data can be manipulated, said that changes in data definitions are unlikely to have long-term negative effects on scientists, but could easily confuse or mislead the layperson.
“When numbers are presented in a flattering light, an expert will generally be able to see through the dazzle quite quickly,” Harford said. “That said, I still think the truthful-yet-deceptive framing of numbers is a serious problem.”
When data are subtly distorted or presented differently than expected — something Harford called “statistical sleight of hand” — it can prompt dangerous levels of general mistrust and cynicism, he said.
“COVID is a matter of life and death and people deserve to have information that is both accurate and understandable without having to decode it,” he said.
HOW SERIOUS IS THIS THIRD WAVE?
Current data from Florida also show that cases and hospitalizations are at record levels, although trends seem to have plateaued over the past week.
“What we’re seeing is an active rise in cases where we can’t keep up, an active rise in deaths that, because of using actual date of deaths, has been shifted back in time and we have no idea where we really are,” said Patel, the epidemiologist from Emory University.
This plateau, she said, might not reflect reality.
“It just looks like Florida is unable to count and report its cases fast enough,” she said.
Patel said data indicate the worst has yet to come for Florida, and it’s likely that deaths will surpass past records. But it’s still too soon to know with certainty, she said.
High levels of hospitalizations also tend to correlate with higher levels of deaths, said Dr. Aileen Marty, an infectious disease professor at FIU’s Herbert Wertheim College of Medicine.
“Ultimately, having a lot of people in the hospital at the same time decreases our overall survival,” Marty said.
The more patients there are in the hospital at the same time, the harder it is for medical staff to give quality care for those patients, Marty said. As the number of patients hospitalized keeps going up, hospitals often start running out of supplies, staff and beds she said.
“The end result is that someone who, if they were the only patient they’d survive, and now might not,” she said.
“We won’t know the true magnitude of the loss of life from this summer’s surge until the fall,” said Trepka.
The coronavirus hospitalizedabout 5,100 more Tennesseans than previously reportedover the past 14 months — an increase of more than 20% over prior totals — according to newly backfilled data from the state department of health.
Hospitalizations were underreported by anywhere from one patient to dozens on nearly every day since the start of last summer, according to the new data. The largest share of the unreported hospitalizations occurred during the winter surge.
Tennessee's revised hospitalization total, including the backfilled data, is 29,694.
Sarah Tanksley, a spokesperson for the health department, said the unreported hospitalizations were now revealed because the agency incorporated a new data source from the Tennessee Hospital Association into its COVID-19 tracking efforts.
The hospital association receives patient-level virus data from hospitals, which is more detailed than the facility-level data hospitals provide to the state government, Tanksley said. The health department only recently figured out how to combine the two sources of information, allowing for a more complete accounting of the virus' impact, she said.
Tanksley said a more complete picture of COVID-19 hospitalizations is "helpful in assessing disease severity, impact of vaccination status, demographics of hospitalized patients."
As of Tuesday, Tennessee was reporting an average of about 7,000 infections and 39 deaths from the virus per day. Nearly 3,300 people were hospitalized with the virus, including 79 children. The state is on pace to set a new record for hospitalizations by the end of the week.
A Texas school district announced Monday evening it would close all campuses until Sept. 7 after a second teacher passed away of COVID-19 complications.
Natalia Chansler and David “Andy” McCormick both taught social studies at Connally Independent School District’s junior high school.
“Although they were in the same content area, they were at two different grade levels in two different portions… of the building,” said Assistant Superintendent Jill Bottelberghe. All staff identified as “close contacts” with a known COVID-19 case are asked to get tested every other day, Bottelberghe said.
All of the district’s campuses are set to be closed for a week and students will do remote learning. Buildings will be deep cleaned and sanitized.
The district will also offer testing for the families of the students who might have been in contact with Mr. McCormick and Ms. Chansler.
The district released a statement to all parents and guardians saying, “We know the hardship this may present to families, but we want to do everything we can to ensure the health and safety of our students and team.” For now, the district is asking parents to monitor children for symptoms and alert the school nurse if a child tests positive.
Intravenous metoprolol for severely ill COVID-19 patients on intensive mechanical ventilation was associated with less lung inflammation and better oxygenation, a randomized pilot study in Spain found.
Among 20 patients on ventilation for COVID-related acute respiratory distress syndrome (ARDS), those assigned to 3 days of metoprolol saw lower neutrophil counts in bronchoalveolar lavage at day 4 compared with those who did not receive the beta-blocker (median 14 vs 397 neutrophils/μl, respectively; P=0.016), reported Borja Ibanez, MD, PhD, of the National Center of Cardiovascular Research in Madrid, and colleagues.
Compared with baseline, oxygenation (PaO2:FiO2) improved for patients on IV metoprolol (median 130 to 267; P=0.003), while no change was seen without the treatment, the authors wrote in the Journal of the American College of Cardiology.
"Repurposing metoprolol for COVID-19-associated ARDS appears to be a safe and inexpensive strategy that can alleviate the burden of the COVID-19 pandemic," the authors said.
Metoprolol also decreased neutrophil extracellular traps content and other markers of lung inflammation, such as IL-8, versus baseline, and the intervention group spent fewer days on mechanical ventilation, though this did not reach statistical significance (15.5 vs 21.9 days, P=0.17).
"There is a growing body of literature regarding the role of beta-blockers in a wide variety of critically ill patients with sepsis and before major surgery, acute respiratory distress syndrome, and traumatic brain injury," noted Mourad Senussi, MD, MS, of Baylor St. Luke's Medical Center in Houston, in an accompanying editorial.
"Although a small-sized, single-center study amid a multitude of others exploring potential treatment modalities for COVID-19 -- this study uses a readily available, safe, and inexpensive medication; has a simple study design; and, most importantly, shows biological plausibility," Senussi wrote.
He also noted the selection bias in the study, as "only those patients who are hemodynamically stable enough can receive beta-blockers."
Anywhere from 6% to 18% of COVID cases result in ARDS, requiring intensive care unit (ICU) admission and use of intensive mechanical ventilation, Ibanez and colleagues explained. As the virus rapidly replicates, ARDS develops from activated neutrophils that infiltrate the alveolar space of the lungs. Metoprolol can reduce inflammation, thereby lowering the risk of cardiovascular events.
"Administration of IV beta-blockers has largely been proven to be safe except for patients with acute pump failure," they noted.
From October 2020 to January 2021, the MADRID-COVID trial (Intravenous Metoprolol in Respiratory Distress Due to COVID-19) randomized patients with COVID-19-associated ARDS to IV metoprolol (n=12; 15 mg daily for 3 days) or no metoprolol (n=8). One patient in the intervention arm only received 2 days of metoprolol due to bradycardia.
The cohort included adults up to age 80 (median 60) with SARS-CoV-2 infection confirmed by RT-PCR, systolic blood pressure ≥120 mm Hg, and a minimum heart rate of 60 bpm. Patients were required to be on mechanical ventilation for fewer than 3 days.
The study's main outcomes were metoprolol's effect on lung inflammation and respiratory function. Before and after randomization, patients in both groups underwent bronchoalveolar lavage. ICU patients were given anticoagulants, corticosteroids, acetylcysteine, and melatonin.
Baseline patient characteristics did not significantly differ between groups. For comorbidities, hypertension (30%) and dyslipidemia (30%) were most common. One-fourth of patients were previously taking renin-angiotensin system inhibitors.
At baseline, there were no between-group differences in neutrophil count. No side effects were reported from the use of metoprolol. While most were discharged, one patient from each group died.
Other limitations of the study included the open-label treatment administration, the authors acknowledged.
Disclosures
Funding for the study was provided by the Spanish government.
Ibanez reported support from the European Commission and one co-author reported support from a Madrid governmental program as well. No additional conflicts were reported.
