Measuring covid-19 related deaths

 Excess mortality. Measuring the direct and indirect impact of COVID-19

Estimations of excess mortality can give an overall understanding of the impact of  COVID-19, by not only comparing deaths that are directly attributable to the virus, but also by 
taking into account indirect mortality. There may be, for example, deaths due to health systems not being able to cope with other conditions or to the longer-term impact of the pandemic on population health. There has been preliminary evidence of disruptions to continuity of care, hindering people suffering from heart attacks, strokes and other conditions from seeking necessary treatment in emergency rooms, or of delays in accessing regular preventive or ongoing care in primary care practitioner (GP), surgeries or outpatient departments for chronic conditions.

And a clear message on this OECD report:

 Comparing the number of reported deaths from all causes against the average over the previous five years, Spain recorded a 61% increase in overall mortality over this 10-week period. At the beginning of April (Week 14), Spain also recorded the highest excess mortality for a single week, with a 154% increase in mortality, equating to more than 12 500 additional deaths compared to the 5-year average for the same week.

The politics of care in US

The Politics of Care. From COVID-19 to Black Lives Matter. Edited by Boston Review

After the US elections, now it's time to rebuild. A new book provides some insights.

WHERE DO WE GO from here? Our answer must connect to a broader politics that addresses the deep structural roots of the problems we face in the United States. We must build for a better future, not just climb out of the rubble of this pandemic, brush ourselves off, and return to business as usual. We need a new politics of care, one organized around a commitment to universal provision for human needs; countervailing power for workers, people of color, and the vulnerable; and a rejection of carceral approaches to social problems. The question now is how to connect that vision to programmatic responses that address the needs of the moment and beyond. We need to aim at “non-reformist reforms”—reforms that embody a vision of the different world we want, and that work from a theory of power-building that recognizes that real change requires changing who has a say in our political process.

The proposals from the progressive wing of the Democratic Party, and even those from democratic socialists, are missing what we might call a New Deal for Public Health. Here, social movements are indispensable. In particular, the AIDS movement of the past forty years offers a template for the kinds of mobilization we’ll need to achieve our goals: not only bringing the virus under control, but also building a future where something like this never happens again.

What might that include? The Medicare for All component has been mapped out, but less obvious and just as crucial is a new, robust, long-lasting infrastructure of care. For example, people need to be able to stay home when they are sick. Yet employment in this country systematically undermines our ability to care for ourselves and others. Women have it the worst, especially immigrant women and women of color, for they are the ones with the highest burdens of paid and unpaid care. The truth is stark: more than 32 million workers lack access to paid sick days. While 93 percent of the highest-wage workers have access to paid sick days, only 30 percent of the lowest-wage workers do. The risk of job loss and precarious scheduling all add to employees’ difficulties. Without anything like universal sick pay or income insurance, self-employed and gig economy workers are cast adrift at a time like this.

Diagnostic Testing for the COVID-19 Pandemic (again)

 Rapid Expert Consultation on Critical Issues in Diagnostic Testing for the COVID-19 Pandemic

Yesterday I was thinking about the implications of having spare structural capacity in hospitals for pandemics and disasters. With a larger capacity, the need for lockdown to preserve health system operations would be less important. However, how much capacity is needed is uncertain. Therefore, the cost and benefit of spare capacity of the health system is very difficult to estimate. And I would add, it is really much more difficult to manage such investment, because spare capacity in physical terms is not enough, you would need also spare capacity in human resources!. Maybe there is a technological innovation that I can foresee. Forget it. 

Right now the hotest issue are the tests and the vaccine. And NASEM has released a rapid consultation of interest about tests.

This rapid expert consultation draws attention to four critical areas in developing diagnostic testing and strategies to reduce the number of COVID-19 infections and deaths: (1) advantages and limitations of reverse transcription polymerase chain reaction (RT-PCR) testing for viral RNA; (2) the status of POC testing; (3) testing strategies, namely, considerations in the deployment of types and sequences of tests; and (4) next-generation testing that offers the prospect of highthroughput, rapid, and less expensive testing.

If you want to know the state of the art, this is the document to read. I can't see anywhere any cost-benefit approach of different options...We are still dealing with precision and accuracy, i.e. effectiveness.

PS. Quite surprising that today everybody is talking about a vaccine and its 90% effectiveness without any scientific paper being published. Can you accept that?. Information merchants looking for attention.

 

Editing human genome

 MODERN PROMETHEUS. Editing the Human Genome with Crispr-Cas9

Drug approval and geographic differences

 Approval of Cancer Drugs With Uncertain Therapeutic Value: A Comparison of Regulatory Decisions in Europe and the United States

We know that the regulation of medical devices is quite different between US and Europe, and with COVID tests we have experienced such divide. In drugs, one could expect a closer approach to approval. However, this is not the case. 

Regulatory agencies may have limited evidence on the clinical benefits and harms of new drugs when deciding whether new therapeutic agents are allowed to enter the market and under which conditions, including whether approval is granted under special regulatory pathways and obligations to address knowledge gaps through postmarketing studies are imposed.

In a matched comparison of marketing applications for cancer drugs of uncertain therapeutic value reviewed by both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), we found frequent discordance between the two agencies on regulatory outcomes and the use of special regulatory pathways. Both agencies often granted regular approval, even when the other agency judged there to be substantial uncertainty about drug benefits and risks that needed to be resolved through additional studies in the postmarketing period.

Postmarketing studies imposed by regulators under special approval pathways to address remaining questions of efficacy and safety may not be suited to deliver timely, confirmatory evidence due to shortcomings in study design and delays, raising questions over the suitability of the FDA’s Accelerated Approval and the EMA’s Conditional Marketing Authorization as tools for allowing early market access for cancer drugs while maintaining rigorous regulatory standards.

 Hockney

The long and bumpy road to CRISPR (2)

 Editing Humanity. The CRISPR Revolution and the New Era of Genome Editing

In 2017 I wrote a post about the book by Jennifer Doudna, A Crack in Creation, now Kevin Davies, the editor of the CRISPR journal has published a new book on CRISPR. It is an effort to put all the information and details about CRISPR in one book. Therefore, if you want to now the whole story (or close to) this is the book to read. If you are interested in a general approach, then the Doudna book is better.

It is quite relevant the chapter that explains the role of Francis Mojica in CRISPR (chapter 3), and the chapter 18, on crossing the germline and what happened about the scandal of genome editing by JK.

“When science moves faster than moral understanding,” Harvard philosopher Michael Sandel wrote in 2004, “men and women struggle to articulate their own unease.” The genomic revolution has induced “a kind of moral vertigo.”49 That unease has been triggered numerous times before and after the genetic engineering revolution—the structure of the double helix, the solution of the genetic code, the recombinant DNA revolution, prenatal genetic diagnosis, embryonic stem cells, and the cloning of Dolly. “Test tube baby” was an epithet in many circles but five million IVF babies are an effective riposte to critics of assisted reproductive technology.

With CRISPR, history is repeating itself,

That's it, great book.

 

NGS: from research to clinical use

 Expanding Use of Clinical Genome Sequencing and the Need for More Data on Implementation

During the past 5 years, next-generation sequencing (NGS) has transitioned from research to clinical use.At least 14 countries have created initiatives to sequence large populations (eg, All of Us, Genomics England), and it is projected that more than 60 million people worldwide will have their genome  sequenced by 2025.

If this is so,

 Understanding how NGS is being used and paid for is critical for determining its clinical and economic benefits and addressing current and future challenges to appropriate implementation.

 Without consistent information on clinical utility and how NGS tests are implemented in clinical care, it is not possible to develop an understanding of benefits and harms associated with NGS. It is not always the case that evidence of clinical utility leads to improved outcomes, and evidence about implementation is required to complete the assessment of the effects on population health. Implementation science is intended to support the integration of findings from scientific evidence to uptake in routine clinical care in the ongoing cycle of a learning health care system.

This is clearly a call for action. However, in my country the call is for both developing NGS  (nothing has started) and asessing implementation. Is there anybody in the room?

Hockney