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Tuesday, July 2, 2019

Mortality rates are still rising in the UK

When the UK’s annual mid-year population estimates were released in late June 2019, much of the media coverage focused on the fact that the population had risen, but growth rates had stalled. The Express newspaper reported that the total population rise of just under 400,000 in the year to mid-2018 was still fuelled by immigration, and that: “The surge is the equivalent of adding a city the size of Coventry to the country.”
But what reporting on this data missed were the 623,000 deaths in the year to mid-2018. This was 20,000 more than the previous year—a 3 percent increase. That is startling because it continues a rise in mortality that began with the first significant fall in UK life expectancy in 2014 and means that UK life expectancy will still be lower today than it was then, five long years ago.
The mid-year population estimates also reveal by how much the population has aged, and that the rise in mortality is not due to aging. As mortality rates for almost all age groups have risen, for both men and women, overall life expectancy will have fallen yet again.
When, in August 2018, the Office for National Statistics (ONS) compared the UK with 19 other countries, mostly in Europe, but also including the US and Japan, it found that only the UK had seen such a large fall in life expectancy since 2014, for both men and women. We now know that has continued through to at least the end of the summer of 2018.
Digging into the data
The fact that nobody appears to have noticed is largely due to the volume of data journalists needed to sift through to find this out and because the ONS didn’t point them towards the significance of continued mortality rises in its press release,
Anyone who wants to know what has actually happened most recently to mortality rates in the UK has to download a huge dataset from the ONS website titled: “MYBE2_detailed components of change series”.
The data is very detailed. For instance, it shows that in Coventry more men aged 86, 87, 88, 89 and 90+ died in the year to mid-2018 than the year before. The spreadsheet also revealed, using NHS patient registrations, that the rise in mortality of very elderly men in Coventry was not due to a sudden influx of people aged over 90-years-old—in fact more left than arrived. It even goes as far as to explain that only three men aged 90 or more arrived into Coventry from outside the UK that year.
Mortality rates are still rising in the UK – and everyone is ignoring how many more people are dying
Source: Analysis of Office for National Statistics June 2019 Mid-Year Estimates. Credit: The Conversation
But Coventry is too small an area to try to examine for reliable trends in just one year for this one small age group. So I combined all the data for all the local authorities in England and Wales to see what has happened.
The table above shows that, overall, 9,493 more men died in England between the summer of 2017 and 2018 and the preceding 12 months—a rise of 3 percent. There was a rise in mortality rates for most age groups, of which the largest relative rise year-on-year was a 14 percent increase in the rate of mortality of boys aged five to nine.
The table above includes the absolute rise per million people at risk. “At risk” just means being alive at the start of the period, in June 2017. The changes in risk are for each group dying in the subsequent 12 months compared to the same aged group over the 12 months before. Everyone resident in England is included in the groups “at risk”. By that measure, an additional nine boys aged between five and nine-years-old died for every one million alive at the start of the year, compared to the previous year.
For some age groups there has been a rise in deaths—for instance of 802 more women aged 70-74—but a fall in the death rates as the population at risk rose faster than the number of deaths. However, such examples are rare.
Rising mortality
For men, the largest rise per million people alive was an extra 3,459 deaths for all men aged 90+. This means that the large increase in deaths in this age group was not due to many more people aged 89 becoming aged 90. It was not due to the aging within the group, nor was it due to a sudden increase in inward migration of very elderly men into Britain (returning from Spain perhaps due to concern over their future health care and Brexit). Instead the rise in mortality is real.
Women did a little better than men according to these latest figures—and the table above shows a 2 percent rise in age-adjusted mortality rates in the year to summer 2018. But in earlier years it’s been mostly women who’ve died in the greatest increasing numbers. For women in England the highest rise in  has been for those in their 90s with an additional 2,504 dying of these oldest ages—an additional 6,358 per million at risk. This is the largest rise of all shown in the table above.
On a graph, the trend of the continued increases in mortality in England is a little more shocking. Only men and women aged 70-74 have experienced the usual improvements in life expectancy that should occur in a normal year for every single age group. The UK has not had a “normal” year when it comes to mortality for at least seven years now.
Mortality rates are still rising in the UK – and everyone is ignoring how many more people are dying
Source: Analysis of Office for National Statistics June 2019 Mid-Year Estimates. Credit: The Conversation
The larger changes shown in the table above will not be due to random variation because the population of England is so large. But for children—for whom death is far less common—random factors can be important when considering annual changes. The rise of two deaths of girls aged between five and nine could be due to chance events, road crashes, childhood cancer, or just neglect. But add the numbers up over recent years and these rates do not rise again and again due to chance.
Warnings for the future
Something is going very wrong. And whatever is going on is unique to the UK because in no other European country have there been overall falls in life expectancy that look at all like this. The figures for Scotland, Wales and Northern Ireland are almost certainly as bad as England, but no one has as yet bothered to study them in any detail—let alone tried to work out where they are heading.
ONS has left some clues about why this is happening. Its statisticians say that currently: “Some 45 local authorities now have falling population.” And they explain that there were also very few births between the summer 2017 and summer of 2018, just 744,000 for the UK as a whole. That’s a remarkable fall of 69,000 births since the year that began in the summer of 2011, when births would have been due to conceptions in early autumn 2010 onwards. We forget how much better things were in 2010, how much more optimistic many of us then felt to start a family, despite the great financial crash of 2008.
The rise in UK mortality began with elderly women and became very clear by February 2014. In June 2016, it was ONS mid-year estimates released on the day of the Brexit referendum result that revealed the rise in mortality rate from earlier to now be accelerating. Few noticed as Brexit transfixed us. In 2017, new ONS figures revealed that a million future years of life in Britain were no longer forecast to be lived. By March 2019, the actuaries of the UK had declared that this change was now established for all  including new born infants.
Ask yourself this: why do we care so little that we cannot even be bothered to analyze and interrogate our mortality statistics properly? Why, when infant  has risen each year from 2014 onwards—from 3.6 to 3.7 to 3.8 to 3.9 children dying per 1,000 born—do we not care? Why instead are we lamenting that there are still gross annual immigration rates equivalent to the population of the city of Coventry?
We should realize that with birth rates falling and more and more people dying more quickly than those the same age as them were in the past, as well as more falling ill, we will soon need all the people we can get.

HIV eliminated from the genomes of living animals

In a major collaborative effort, researchers at the Lewis Katz School of Medicine at Temple University and the University of Nebraska Medical Center (UNMC) have for the first time eliminated replication-competent HIV-1 DNA—the virus responsible for AIDS—from the genomes of living animals. The study, reported online July 2 in the journal Nature Communications, marks a critical step toward the development of a possible cure for human HIV infection.
“Our study shows that treatment to suppress HIV replication and gene editing therapy, when given sequentially, can eliminate HIV from cells and organs of infected animals,” said Kamel Khalili, Ph.D., Laura H. Carnell Professor and Chair of the Department of Neuroscience, Director of the Center for Neurovirology, and Director of the Comprehensive NeuroAIDS Center at the Lewis Katz School of Medicine at Temple University (LKSOM). Dr. Khalili and Howard Gendelman, MD, Margaret R. Larson Professor of Infectious Diseases and Internal Medicine, Chair of the Department of Pharmacology and Experimental Neuroscience and Director of the Center for Neurodegenerative Diseases at UNMC, were senior investigators on the new study.
“This achievement could not have been possible without an extraordinary team effort that included virologists, immunologists, molecular biologists, pharmacologists, and pharmaceutical experts,” Dr. Gendelman said. “Only by pooling our resources together were we able to make this groundbreaking discovery.”
Current HIV treatment focuses on the use of antiretroviral therapy (ART). ART suppresses HIV replication but does not eliminate the virus from the body. Therefore, ART is not a cure for HIV, and it requires life-long use. If it is stopped, HIV rebounds, renewing replication and fueling the development of AIDS. HIV rebound is directly attributed to the ability of the virus to integrate its DNA sequence into the genomes of cells of the immune system, where it lies dormant and beyond the reach of antiretroviral drugs.
In previous work, Dr. Khalili’s team used CRISPR-Cas9 technology to develop a novel gene editing and gene therapy delivery system aimed at removing HIV DNA from genomes harboring the virus. In rats and mice, they showed that the gene editing system could effectively excise large fragments of HIV DNA from infected cells, significantly impacting viral gene expression. Similar to ART, however, gene editing cannot completely eliminate HIV on its own.
For the new study, Dr. Khalili and colleagues combined their gene editing system with a recently developed therapeutic strategy known as long-acting slow-effective release (LASER) ART. LASER ART was co-developed by Dr. Gendelman and Benson Edagwa, Ph.D., Assistant Professor of Pharmacology at UNMC.
LASER ART targets viral sanctuaries and maintains HIV replication at low levels for extended periods of time, reducing the frequency of ART administration. The long-lasting medications were made possible by pharmacological changes in the chemical structure of the antiretroviral drugs. The modified drug was packaged into nanocrystals, which readily distribute to tissues where HIV is likely to be lying dormant. From there, the nanocrystals, stored within cells for weeks, slowly release the drug.
According to Dr. Khalili, “We wanted to see whether LASER ART could suppress HIV replication long enough for CRISPR-Cas9 to completely rid cells of viral DNA.”
To test their idea, the researchers used mice engineered to produce human T cells susceptible to HIV infection, permitting long-term viral infection and ART-induced latency. Once infection was established, mice were treated with LASER ART and subsequently with CRISPR-Cas9. At the end of the treatment period, mice were examined for viral load. Analyses revealed complete elimination of HIV DNA in about one-third of HIV-infected mice.
“The big message of this work is that it takes both CRISPR-Cas9 and virus suppression through a method such as LASER ART, administered together, to produce a cure for HIV infection,” Dr. Khalili said. “We now have a clear path to move ahead to trials in non-human primates and possibly clinical trials in human patients within the year.”

Explore further

More information: Sequential LASER ART and CRISPR Treatments Eliminate HIV-1 in a Subset of Infected Humanized Mice, Nature Communications (2019). DOI: 10.1038/s41467-019-10366-y , https://nature.com/articles/s41467-019-10366-y

Concussion rates nearly double what we think—and summer is prime injury time

With concussions seeming more common than ever before, researchers at Toronto Rehabilitation Institute—University Health Network, set out to answer the question, Are we looking at a true epidemic, or just better recognition?
By embarking on the largest-scale study on concussions ever undertaken in Canada, the researchers discovered that 150,000 of Ontarians (1.2% of province’s population) are diagnosed with a concussion each year. That’s almost twice as high as previously recorded, and may represent a closer estimate of the true picture of concussion in Ontario.
Their findings were published the Journal of Head Trauma Rehabilitation.
“Past research has looked at the incidence of concussion by examining a particular population; cause of injury; or use a single reporting source, such as records from the Emergency Department. This can under-represent estimates of the real incidence of concussion,” says lead author, Laura Langer.
“Our study revealed concussion rates that are almost double what has been previously reported, and highlights the critical importance of looking at everyone who sought medical attention for their concussion.”
These more accurate estimates support the importance ongoing awareness around  and management, and the need for more specialized concussion clinics near populations that need them the most.
Concussions in Ontario—who is at risk?
By leveraging the ICES Data Repository—a province-wide archive that integrates multiple clinical and administrative health databases—the team captured an unprecedented, comprehensive, view of concussion rates in Ontario between 2008 and 2016.
Here is what they found:
  • About 150,000 Ontarians experience a concussion each year
  • Children under 5 years old experience the highest rate of concussion among all Ontarians
  • Adults over 65—especially women—experience a higher rate of concussion than younger adults
  • 26% all of concussions are diagnosed in the summer
  • Rural communities experience a higher rate of concussion than non-rural communities
  • Though most concussions are diagnosed in the Emergency Department, more and more patients with concussion symptoms are visiting their own doctors
Epidemic or better recognition?
According to the team, the high rate of reported concussions is likely influenced by a number of factors, including increased  from athletes and the media, new mandatory reporting laws, and the release of numerous diagnostic and management guidelines for physicians and patients.
Future directions
Access to the ICES Data Repository presents a unique opportunity for Ontario to be a world leader in concussion care and research.
As patients increasingly look to their own doctors for a diagnosis, the researchers identify a need to continue raising awareness about causes and symptoms, and a growing obligation to educate doctors on concussion care.
Furthermore, since about 1 in 7 Ontarians with a  will experience persistent, post-concussive symptoms, it’s critical to develop tools to identify who will face long-term problems, so we can individualize early treatments to prevent long-term complications.
The study was funded by, and conducted in collaboration with, Ontario Neurotrauma Foundation. Toronto Rehabilitation Institute is also financially supported by the Toronto Rehab Foundation.
This study made use of de-identified data from the ICES Data Repository, which is managed by ICES, a non-profit research institute that uses population-based health information to produce knowledge on a broad range of health care issues.

Explore further

More information: Laura Langer et al. Increasing Incidence of Concussion: True Epidemic or Better Recognition?Journal of Head Trauma Rehabilitation: June 25, 2019.

Cholesterol that is too low may boost risk for hemorrhagic stroke

Current guidelines recommend lowering cholesterol for heart disease risk reduction. New findings indicate that if cholesterol dips too low, it may boost the risk of hemorrhagic stroke, according to researchers.
Over a period of nine years, a Penn State-led study examined the relationship between —LDL, commonly known as “bad” —and hemorrhagic stroke. This type of stroke occurs when a blood vessel bursts in the brain.
The researchers found that participants with LDL cholesterol levels below 70 mg/dL had a higher risk of hemorrhagic stroke.
Xiang Gao, associate professor of nutritional sciences and director of the Nutritional Epidemiology Lab at Penn State, said the results—published today (date) in Neurology—may help refine and personalize recommendations for ideal target cholesterol levels.
“As is true with many things in nutrition, moderation and balance is key when deciding the optimal target level of LDL cholesterol,” Gao said. “You can’t go to either extreme—too high or too low. And if you’re at a high risk for hemorrhagic stroke due to family history or risk factors like  and heavy alcohol drinking, you may want to be extra careful about LDL cholesterol levels.”
According to the researchers, low LDL cholesterol is recommended as a way to reduce the risk of a heart attack or ischemic stroke—the latter when a blood vessel in the brain becomes blocked by a clot. But previous research has suggested a link between very low LDL cholesterol levels and hemorrhagic stroke.
Chaoran Ma, a nutritional sciences graduate student at Penn State, said that while previous studies suggested this connection, there was a need for additional validation in a separate cohort.
“For our study, we wanted to expand the scope of knowledge in this area by investigating the issue prospectively in a large cohort with multiple LDL cholesterol measurements to capture variation over time,” Ma said.
The study included 96,043 participants with no history of stroke, heart attack or cancer when the study began. LDL cholesterol levels were measured when the study began and yearly thereafter for nine years. Reported incidents of hemorrhagic stroke were confirmed by medical records.
The researchers found that participants who had LDL cholesterol levels between 70 and 99 mg/dL had a similar risk of hemorrhagic stroke. But, when LDL cholesterol levels dipped below 70 mg/dL, the risk of hemorrhagic  increased significantly. For example, the risk increased by 169 percent for participants with LDL levels less than 50mg/dL relative to those with LDL levels between 70 and 99 mg/dL. These findings were consistent after controlling for age, sex, blood pressure and medication.
“Traditionally, an LDL cholesterol level of more than 100 mg/dL had been considered as optimal for the general population and lower in individuals at elevated risk of heart disease,” Gao said. “We observed that the risk of  increased in individuals with LDL cholesterol levels below 70 mg/dL. This observation, if confirmed, has important implications for treatment targets.”
Ma said the findings may be able to help health care professionals continue to refine guidelines.
“The results were based on a large community-based study, which is an advantage because it focused on healthy people in a non-clinical setting,” Ma said.

States agree to pause lawsuits against bankrupt opioid maker Insys

Five states have agreed to facilitate settlement talks by dropping objections to a bid by Insys Therapeutics Inc (INSYQ.PK) in bankruptcy court to put on hold their lawsuits alleging the drugmaker helped fuel the opioid epidemic.
The agreement was announced on Tuesday by a lawyer for Chandler, Arizona-based Insys during a hearing before a federal bankruptcy judge in Wilmington Delaware, who was set to consider whether to block the states from moving forward with their cases.
Insys requested the injunction when it filed for Chapter 11 bankruptcy protection on June 10, becoming the first drugmaker accused in lawsuits by state and local governments of contributing to the deadly opioid epidemic to do so.
Insys filed for bankruptcy days after striking a $225 million settlement with the Justice Department resolving claims it paid doctors bribes to prescribe Subsys, the company’s addictive fentanyl spray.
A federal jury in Boston in May found Insys founder John Kapoor and four other former executives guilty of engaging in a racketeering conspiracy involving Subsys marketing practices.

Filing for bankruptcy normally halts active litigation against a company while it reorganizes. But a longstanding exception in U.S. bankruptcy law allows for lawsuits to proceed enforcing government officials’ “police powers.”
Lawyers for Maryland and Minnesota, where Insys faced upcoming administrative trials in August and September, last week opposed Insys’ motion to stay their cases, citing that exception. New York, New Jersey and Arizona joined them.
A ruling on Insys’ motion could have influenced whether OxyContin maker Purdue Pharma LP – another opioid manufacturer facing some 2,000 lawsuits – decides to file for bankruptcy protection, according to a person familiar with the matter and legal experts.
But at Tuesday’s hearing, Ronit Berkovich, a lawyer for Insys, told U.S. Bankruptcy Judge Kevin Gross that the five states, as well as North Carolina, had agreed to stay their cases in order to support a settlement negotiation protocol.
After hearing arguments over the proposal’s merits, Gross agreed to approve it, saying it initiates negotiations that need to take place to avoid draining cash-strapped Insys of money.

“We don’t want to reduce that money by litigating and the like,” he said.
Cities and counties pursuing hundreds of similar cases against Insys are not part of the deal, nor are several states that had already agreed to put their lawsuits on hold.
But Berkovich said they would be invited to participate in the negotiation process, which she said envisions putting Insys in a position to file a restructuring plan for the court’s approval by Sept. 2.

Invacare cuts 75 jobs, names new sales roles

In a progress update on its transformation plan, Invacare (NYSE:IVC) says it’s cut 75 jobs and changed some leadership in its sales organization.
The company named Joost Beltman VP – Sales and Marketing, North America. Most recently, he served as managing director of the Benelux and Italy regions.
It’s also named Keith Brantly director of CRT sales; he’s rejoining the company from Amoena USA.
Meanwhile, it’s shed 75 associates in North America and Europe. The company expects pretax cash restructuring charges of about $0.6M in Q2 and $2.5M in Q3.
Once the workforce reduction is done, it expects $6.4M in annualized pretax savings: $3.3M in Europe, and the rest in North America.

Mizuho starts Merck at Buy