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Posts Tagged ‘Mortality rate’


Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

One of the most contagious diseases known to humankind, measles killed an average of 2.6 million people each year before a vaccine was developed, according to the World Health Organization. Widespread vaccination has slashed the death toll. However, lack of access to vaccination and refusal to get vaccinated means measles still infects more than 7 million people and kills more than 100,000 each year worldwide as reported by WHO. The cases are on the rise, tripling in early 2019 and some experience well-known long-term consequences, including brain damage and vision and hearing loss. Previous epidemiological research into immune amnesia suggests that death rates attributed to measles could be even higher, accounting for as much as 50 percent of all childhood mortality.

 

Over the last decade, evidence has mounted that the measles vaccine protects in two ways. It prevents the well-known acute illness with spots and fever and also appears to protect from other infections over the long term by giving general boost to the immune system. The measles virus can impair the body’s immune memory, causing so-called immune amnesia. By protecting against measles infection, the vaccine prevents the body from losing or “forgetting” its immune memory and preserves its resistance to other infections. Researchers showed that the measles virus wipes out 11% to 73% of the different antibodies that protect against viral and bacterial strains a person was previously immune to like from influenza to herpes virus to bacteria that cause pneumonia and skin infections.

 

This study at Harvard Medical School and their collaborators is the first to measure the immune damage caused by the virus and underscores the value of preventing measles infection through vaccination. The discovery that measles depletes people’s antibody repertoires, partially obliterating immune memory to most previously encountered pathogens, supports the immune amnesia hypothesis. It was found that those who survive measles gradually regain their previous immunity to other viruses and bacteria as they get re-exposed to them. But because this process may take months to years, people remain vulnerable in the meantime to serious complications of those infections and thus booster shots of routine vaccines may be required.

 

VirScan detects antiviral and antibacterial antibodies in the blood that result from current or past encounters with viruses and bacteria, giving an overall snapshot of the immune system. Researchers gathered blood samples from unvaccinated children during a 2013 measles outbreak in the Netherlands and used VirScan to measure antibodies before and two months after infection in 77 children who’d contracted the disease. The researchers also compared the measurements to those of 115 uninfected children and adults. Researchers found a striking drop in antibodies from other pathogens in the measles-infected children that clearly suggested a direct effect on the immune system resembling measles-induced immune amnesia.

 

Further tests revealed that severe measles infection reduced people’s overall immunity more than mild infection. This could be particularly problematic for certain categories of children and adults, the researchers said. The present study observed the effects in previously healthy children only. But, measles is known to hit malnourished children much harder, the degree of immune amnesia and its effects could be even more severe in less healthy populations. Inoculation with the MMR (measles, mumps, rubella) vaccine did not impair children’s overall immunity. The results align with decades of research. Ensuring widespread vaccination against measles would not only help prevent the expected 120,000 deaths that will be directly attributed to measles this year alone, but could also avert potentially hundreds of thousands of additional deaths attributable to the lasting damage to the immune system.

 

References:

 

https://hms.harvard.edu/news/inside-immune-amnesia?utm_source=Silverpop

 

https://science.sciencemag.org/content/366/6465/599

 

www.who.int/immunization/newsroom/measles-data-2019/en/

 

https://www.ncbi.nlm.nih.gov/pubmed/20636817

 

https://www.ncbi.nlm.nih.gov/pubmed/27157064

 

https://www.ncbi.nlm.nih.gov/pubmed/30797735

 

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Carotid Stenting: Vascular surgeons have pointed to more minor strokes in the stenting group and cardiologists to more myocardial infarctions in the CEA cohort.

Reporter: Aviva Lev-Ari, PhD,RN

Why CREST is a Game Changer for Carotid Stenting

 

Speaker: Gary Roubin, MD, PhD

The CREST Trial was the largest, most rigorous and because of the way it was conducted, the most relevant investigation into the role of carotid stenting to date.

The National Institute of Neurological Diseases after critical review concluded that the study “Demonstrated that Endarterectomy and Stenting were equally efficacious methods of preventing stroke caused by carotid bifurcation stenoses.”

The primary endpoint was unequivocal but the components of this combined endpoint have been dissected by various groups to support different conclusions. Vascular surgeons have pointed to more minor strokes in the stenting group and cardiologists to more myocardial infarctions in the CEA cohort. The CREST Trial demonstrated remarkable safety from both procedures with a very low and similar major stroke and death rate.  The small numbers of excess strokes in the stenting group were minor strokes and importantly further analyses of temporal trends have demonstrated this delta disappeared over the course of the study.  Stenting stroke rates improved over time probably related to better selection of younger patients with more suitable anatomy for stenting.

If CREST was to restart in 2012, it is extremely unlikely that any difference whatsoever would be seen in comparing CEA and Stenting.

Importantly, minor strokes were not associated with a later excess mortality while a periprocedural MI was associated with death over the follow up period.

Quality of life analyses reflected the minor, non disabling nature of the small number of excess minor strokes.  The comprehensive panel of SF36 mental and physical quality of life measures demonstrated no difference whatsoever between stenting and CEA.

Despite completing the study with first generation stents and embolic protection devices, the outcomes were gratifying.  A critical FDA panel subsequently approved the extension of labeling for stenting use in standard risk CEA patients.

Now we await a considered response from CMS to acknowledge the demonstration of “reasonable safety and efficacy” and long awaited reimbursement for this patient friendly, percutaneous procedure.

We now are experiencing a curious push back from some in the neurological community and even some surgeons who argue that neither CEA nor stenting are needed in the treatment of asymptomatic patients. 

  • This—despite multiple trials that have demonstrated the superiority of revascularization and markedly improved revascularization results.
  • This—despite no scientific evidence to support the equivalence of medical therapy in preventing stroke in carotid bifurcation disease.

 

Panel Discussion

 

NICK HOPKINS

The CREST data stand on their own merits. Looking at the survival curves for minor stroke versus myocardial infarction, as a surgeon who does a large volume of CEA and stenting, I am impressed with the benign outcome in the minor strokes and the bad outcomes associated with M.I. Again, as a surgeon, I doubt we can do anything to reduce the incidence of MI, but as a stent operator, I feel we can do much more to further reduce the incidence of stroke events.

For example, the neurological community has focused on the ICSS Trial sub-study that demonstrated a significant incidence of MRI-DWI defects after stenting. We don’t really know what DWI changes mean but the neurological community assumes they are bad.  We see a 15-20% incidence with just a routine angiogram and they are probably just micro-bubbles causing these temporary defects. In the ICSS trials, the incidence of these lesions was 50% in the stent arm and 12% in the CEA arm.   The conclusion was that stenting was “bad” but embolic protection devices were only used in 75% of the ICSS patients. Now we have new devices such as proximal occlusion balloons that have been shown to markedly reduce the incidence of these lesions. So, this is just one example of new stenting techniques that will reduce the incidence of stroke to even lower rates. There is also a lot of activity in the industry to make carotid stents covered with a fine, semi-permeable membrane that will reduce the chance of embolic debris from the procedure. With current devices and certainly the stent used in CREST, debris may be forced through the stent strut when you dilate.

So to me these are just two examples of things that will improve the stroke rate from the current 1% to 3% to near zero.

TY COLLINS

I am not sure what happened at the Medicare Coverage Advisory Meeting last week (January 2012) but basically the committee did not appear to focus on the CREST data.

JIRI VITEK

One of the most important differentiating features of CREST compared to the European Trials was the emphasis on operator credentialing and ongoing training of operators over the 8 years of recruitment.  This is evidenced by the improvement of stent outcomes over the time course of the trial.

I also want to point out that none of these trials place enough emphasis on cranial nerve injuries that are an exclusive and important complication of CEA.  In CREST there was a 4.5% incidence of cranial nerve palsy in the CEA cohort, and 2% were still present at 6 months.

BARRY KATZEN

I firmly believe that CREST is a “game changer.” I spent a full day at the Medicare Coverage Advisory Committee last week (January 2012). Two things happened. The first was that the entire discussion was derailed by irrelevant discussion of the supposed value of medical therapy. As Ty said before, nobody appeared to be focused on the CREST data but was distracted by arguments about the value of medical management. A neurologist, Anne Abbott, took a large amount of time basically “trouncing” any type of revascularization therapy. 

The critical consideration by the FDA and their approval of the devices for this indication is a better representation of where we stand today. Interdisciplinary factional disputes and politics aside, I believe CMS will want to expand the coverage for carotid stenting in some way.

JIM ZIDAR

I will say that although CREST is a “game changer”, it seems the cards may be stacked against stenting.  Besides the cost issues that may be associated with expanded coverage, they are influenced by the self interest of the Society of Vascular Surgery that decided they were not going to support the data. If coverage is not expanded for stenting, I wonder if it is not unreasonable for other professional societies to conclude and pronounce that CEA should not be reimbursed in asymptomatic patients.

NICK HOPKINS

CMS would be interested in that.  I actually think that given the dialogue on the day, it definitely could have gone that way.

BARRY KATZEN

It is fascinating to think about this. Given all of the level 1 scientific data supporting revascularization over medical therapy, in the United States today, CEA is the standard of care. Primary care physicians throughout the country recommend this for patients with severe stenoses. CMS is basically talking about erasing that standard of care or now an equivalent procedure from a reimbursement standpoint.

GARY ROUBIN

Let us all be clear about the evidence from CREST. In the younger patients, male patients and asymptomatic patients there was no significant difference in outcomes for stroke and death between stenting and CEA. 

 

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Author and Curator: Dror Nir, PhD

The management of men with prostate cancer is becoming one of the most challenging public health issues in the Western world. It is characterized by: over-diagnosis; over-treatment; low treatment efficacy; treatment related toxicity; escalating cost; and unsustainability [Bangma et al, 2007; Esserman et al, 2009]. How come? Well, everyone accepts that most prostate cancers are clinically insignificant. It is well known that all men above 65 harbor some sort of prostate cancer. Due to the current aggressive PSA-based screening, one in six men will be diagnosed with prostate cancer. Yet, the lifetime risk of dying of prostate cancer is only 3%. The problem is that, once diagnosed with prostate cancer, there is no accurate tool to identify those men that will die of the disease (in my previous post I mentioned 1:37). Currently, screening practices for prostate cancer are relying on the very unspecific prostate-specific-antigen (PSA) bio-marker test to determine which men are at higher risk of harboring prostate cancer and therefore need a biopsy. The existing diagnostic test is a transrectal ultrasound (TRUS) guided prostate biopsy aimed at extracting representative tissue from areas where cancer usually resides. This procedure suffers from several obvious faults:

1. Since the imaging tool used (B-mode ultrasound) is poor at detecting malignancies in the prostate, the probability of hitting a clinically significant cancer or missing a clinically insignificant cancer is subject to random error.

2. TRUS biopsy is also subjected to systematic error as it misses large parts of the prostate which might harbor cancer (e.g. apex and anterior zones).
3. TRUS guided biopsies are often unrepresentative of the true burden of cancer as either the volume or grade of cancer can be underestimated.

In the last ten years I was leading the development of an innovative ultrasound-based technology, HistoScanningTM, aimed at improving the aforementioned faults;

Among the other most popular imaging modalities aimed at better prostate cancer detection in routine use are: MRIElastography, Contrast Enhanced Ultrasound etc…

In my future posts I will go into more detail on how these imaging modalities fit into routine workflow, how much they stay within budget constraints and what level of promise they bear for promoting personalized medicine. Stay tuned… Footnote: According to the final report by an advisory panel to the USA government: Doctors should no longer offer the PSA prostate cancer screening test to healthy men because they’re more likely to be harmed by the blood draw, and the chain of medical interventions that often follows than be helped; (http://www.usatoday.com/news/health/story/2012-05-21/prostate-cancer-screening-test-harmful/55118036/1) But then; what should be offered instead?

Other posts on this Scientific Website addressing Prostate Cancer

Prostate Cancers Plunged After USPSTF Guidance, Will It Happen Again?

https://pharmaceuticalintelligence.com/2012/07/31/prostate-cancers-plunged-after-uspstf-guidance-will-it-happen-again/

New Prostate Cancer Screening Guidelines Face a Tough Sell, Study Suggests

https://pharmaceuticalintelligence.com/2012/05/27/new-prostate-cancer-screening-guidelines-face-a-tough-sell-study-suggests/

ROLE OF VIRAL INFECTION IN PROSTATE CANCER

https://pharmaceuticalintelligence.com/2012/09/01/role-of-viral-infection-in-prostate-cancer/

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Aspirin a Day Tied to Lower Cancer Mortality

Reporter: Aviva Lev-Ari, PhD, RN

Aspirin a Day Tied to Lower Cancer Mortality

Download Complimentary Source PDF 

Daily aspirin use is associated with a modest decrease in mortality from cancer, particularly for malignancies of the gastrointestinal tract, a large retrospective study confirmed.

Individuals who were current daily users for 5 years or more at baseline had an 8% decrease in cancer mortality compared with non-users (RR 0.92, 95% CI 0.83 to 1.02), according to Eric J. Jacobs, PhD, and colleagues from the American Cancer Society in Atlanta.

The association was stronger, with a 16% decrease for those with daily use for 5 years or more, when the analysis included data collected periodically during 2 decades of follow-up (RR 0.84, 95% CI 0.75 to 0.95), the researchers reported in the Journal of the National Cancer Institute.

A recent pooled analysis of more than 50 trials involving aspirin use for cardioprotection found a 37% reduction in deaths from cancer among users, which was considerably greater than in observational studies and trials of alternate-day aspirin.

To clarify the magnitude of the association between aspirin use and overall cancer mortality, Jacobs and colleagues analyzed data from the Cancer Prevention Study II, which began in 1992 and included 100,139 participants who completed questionnaires with information on demographics, medical history, and behavioral influences.

Beginning in 1997, participants also provided information about aspirin use, and continued to provide updates every 2 years.

The 1997 questionnaire was considered the baseline for the analysis, at which time 23.8% of participants were using either low-dose or adult-strength aspirin.

More than half of participants were older than 60 and female, and almost all were white.

During the 20 years of follow-up, there were 5,138 deaths from cancer.

Among those who reported aspirin use in 1997, three-quarters said they were still taking it in 2003, while among those who were non-users at baseline, 25% had begun doing so.

Baseline aspirin users tended to be more educated, former smokers, and obese, as well as to have a history of cardiovascular disease and diabetes.

Male users also were more likely to have a history of prostate specific antigen (PSA) testing, and women users were more likely to have a history of mammography.

Overall mortality was slightly lower even for individuals who had been users for less than 5 years (RR 0.84, 95% CI 0.76 to 0.94).

Relative risks were similar for users of low-dose and full-strength aspirin, and for those with and without a history of cardiovascular disease, ranging from 0.82 (95% CI 0.72 to 0.91) to 0.95 (95% CI 0.86 to 1.04).

Current users who had never smoked had considerably lower mortality (RR 0.68, 95% CI 0.57 to 0.81), a reduction that was not seen for former smokers (RR 0.92, 95% CI 0.82 to 1.04) or those currently smoking (RR 0.91, 95% CI 0.70 to 1.19).

Even after discounting lung cancer deaths, the only lower mortality among aspirin users was for never-smokers (RR 0.67, 95% CI 0.56 to 0.81).

A possible explanation for the lack of effect on cancers other than those in the lung among ever-smokers is that smoking may attenuate the antiplatelet activity of aspirin, and activated platelets are thought to promote tumor metastases, the researchers explained.

Aspirin use at the 1997 baseline was not significantly associated with mortality from specific cancers, but differences were seen when data through 2008 were included in the analysis:

  • Cancers within the gastrointestinal tract, RR 0.61 (95% CI 0.44 to 0.84)
  • Cancers outside the gastrointestinal tract, RR 0.88 (95% CI 0.78 to 1)
  • Colorectal cancer, OR 0.64 (95% CI 0.42 to 0.98)
  • Esophageal and stomach cancer, RR 0.56 (95% CI 0.37 to 0.86)

“The reduction in overall cancer mortality was driven by both a substantial reduction in mortality from gastrointestinal tract cancers and a small, but statistically significant, reduction in mortality from cancers outside the gastrointestinal tract,” they stated.

They noted that their study was observational, which was an important limitation, in that confounding factors could have resulted in either an underestimate or an overestimate of the effects of aspirin on mortality.

Also, the absolute risk for cancer mortality between non-users and daily long-term aspirin users — approximately 100 per 100,000 person-years for men and about 40 per 100,000 person-years for women — would represent an important benefit of aspirin use if it were causal, the authors stated.

“However, even if causal, differences in absolute rates are likely to differ between our predominantly elderly population and younger populations at much lower risk of cancer mortality,” they warned.

They concluded that the “relatively modest benefit” seen in their analysis could “meaningfully influence the balances of risks and benefits of prophylactic aspirin use.”

In an accompanying editorial, John Baron, MD, of the University of North Carolina in Chapel Hill, offered a word of caution. Baron was the lead author of the meta-analysis on aspirin use and cancer risk.

“Just because aspirin is effective does not mean it necessarily should be used,” he argued.

“Aspirin is a real drug, with definite toxicity. As for any preventative intervention, the benefits must be balanced against the risks, particularly when the benefits are delayed whereas the risks are not,” Baron stated.

The American Cancer Society funds the Cancer Prevention Study II cohort.

The authors are employees of the American Cancer Society.

Editorialist Baron has been a consultant for Bayer, and holds a use patent for aspirin chemoprevention.

Primary source: Journal of the National Cancer Institute
Source reference:
Jacobs E, et al “Daily aspirin use and cancer mortality in a large US cohort” JNCI 2012; DOI: 10.1093/jnci/djs318.

Additional source: Journal of the National Cancer Institute
Source reference:
Baron JA, et al “Aspirin and cancer: trials and observational studies” JNCI 2012; DOI: 10.1093/jnci/djs318.

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Reporter: Prabodh Kandala, PhD

Scientists know that Vitamin D deficiency is not healthy. However, new research from the University of Copenhagen now indicates that too high a level of the essential vitamin is not good either. The study is based on blood samples from 247,574 Copenhageners. The results have just been published in the reputed scientific Journal of Clinical Endocrinology and Metabolism.

Vitamin D is instrumental in helping calcium reach our bones, thus lessening the risk from falls and the risk of broken hips. Research suggests that vitamin D is also beneficial in combating cardiac disease, depression and certain types of cancers. The results from a study conducted by the Faculty of Health and Medical Sciences now support the benefits of vitamin D in terms of mortality risk. However, the research results also show higher mortality in people with too high levels of vitamin D in their bloodstream:

“We have had access to blood tests from a quarter of a million Copenhageners. We found higher mortality in people with a low level of vitamin D in their blood, but to our surprise, we also found it in people with a high level of vitamin D. We can draw a graph showing that perhaps it is harmful with too little and too much vitamin D,” explains Darshana Durup, PhD student.

If the blood contains less than 10 nanomol (nmol) of vitamin per liter of serum, mortality is 2.31 times higher. However, if the blood contains more than 140 nmol of vitamin per liter of serum, mortality is higher by a factor of 1.42. Both values are compared to 50 nmol of vitamin per liter of serum, where the scientists see the lowest mortality rate.

More studies are needed

Darshana Durup emphasises that while scientists do not know the cause of the higher mortality, she believes that the new results can be used to question the wisdom of those people who claim that you can never get too much vitamin D:

“It is important to conduct further studies in order to understand the relationship. A lot of research has been conducted on the risk of vitamin D deficiency. However, there is no scientific evidence for a ‘more is better’ argument for vitamin D, and our study does not support the argument either. We hope that our study will inspire others to study the cause of higher mortality with a high level of vitamin D,” says Darshana Durup. She adds:

“We have moved into a controversial area that stirs up strong feelings just like debates on global warming and research on nutrition. But our results are based on a quarter of a million blood tests and provide an interesting starting point for further research.”

The largest study of its kind

The study is the largest of its kind — and it was only possible to conduct it because of Denmark’s civil registration system, which is unique in the Nordic countries. The 247,574 blood samples come from the Copenhagen General Practitioners Laboratory:

“Our data material covers a wide age range. The people who participated had approached their own general practitioners for a variety of reasons and had had the vitamin D level in their bloodstream measured in that context. This means that while the study can show a possible association between mortality and a high level of vitamin D, we cannot as yet explain the higher risk,” explains Darshana Durup.

Therefore in future research project scientists would like to compare the results with information from disease registers such as the cancer register. Financial support is currently being sought for such projects.

Ref:

http://www.sciencedaily.com/releases/2012/05/120529102346.htm

http://jcem.endojournals.org/content/early/2012/05/09/jc.2012-1176

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