The Observatory

Jan. 25, 2018
Sickle cell disease (SCD) is the most common form of an inherited blood disorder. Unlike patients with SCD, who have two genes that cause the production of abnormal hemoglobin, individuals with sickle cell trait carry only one defective gene and typically live normal lives without health problems related to sickle cell.

Is the percentage of people in West and Central Africa who have the sickle cell trait.

Is the percentage of all babies born with a form of SCD in West and Central Africa.

Is the number of babies born with SCD each year in Nigeria.

Is the percentage of children with SCD who do not survive to adulthood in resource-poor countries.

1 in 365
Is the number of babies born with SCD each year in the United States.

Is the number of individuals in the United States who have SCD.

3 million
Is the number of individuals in the United States who have sickle cell trait.

Is the percentage of African Americans affected by sickle cell trait.

1 in 12
Is the number of people of African descent (including African Americans) who carry a sickle cell gene.

Is the number of years since researchers first identified SCD.

Sources: and and


Researchers identify genetic factors that contribute to AD. Scientists have identified several new genes responsible for Alzheimer’s disease (AD), including those leading to functional and structural changes in the brain and elevated levels of AD proteins in cerebrospinal fluid.

Unlike traditional AD research, this Boston University School of Medicine study focused on individual groups across the cognitive spectrum (normal cognitive functioning or controls, mild cognitive impairment, and AD cases). As opposed to the typical study design which combines all such persons into a single group or focuses only on cognitively healthy persons, this research identified several novel genetic associations within multiple subgroups.

According to the researchers, these associations are not evident when comparing AD cases to controls or within AD cases, suggesting that these signals underlie processes before onset of AD. As such, these genes may be more attractive targets for drug development, because it is increasingly recognized that effective drugs will be those given to persons before or shortly after they develop cognitive impairment.

The researchers tested the association between AD-related brain MRI measures, logical memory test scores, and cerebrospinal fluid levels of two AD proteins (amyloid-beta and tau) with several million genetic markers (single nucleotide polymorphisms, or SNPs) across the genome in a sample of 1,189 participants in the Alzheimer Disease Neuroimaging Initiative study. They then examined the biological significance of the top-ranked associated SNPs and genes using several data sets containing information about gene expression in parts of the brain most affected by AD.

Two of the study-wide significant genes identified in the normal cognitive functioning group, SRRM4 and MTUS1, are involved in neuronal signaling, development, and loss. Another gene identified in this group, GRIN2B, encodes a subunit of a receptor that has roles in resilience of neurons and memory.

Infectious Diseases

Zika remains a research and public health challenge. Since 2016, when Zika was declared by the World Health Organization (WHO) to be a public health emergency of international concern, the virus has become established in more than 80 countries, has infected millions of people, and has left many babies with birth defects. Although scientists have made progress in understanding the virus and its mosquito carrier and are working toward treatments and a preventive vaccine, it would be premature to think that the Zika pandemic is now under control and will not reemerge, perhaps more aggressively. So say leaders from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).

The Journal of Infectious Diseases recently published online a special supplement of articles examining current scientific knowledge about ZIKV and the key research questions that remain. It features several articles written by NIAID scientists.

The journal’s introductory article was written by NIAID director Anthony S. Fauci, MD, and senior advisor David Morens, MD. It notes some of the critical scientific issues regarding Zika that deserve further exploration, including: whether certain viral mutations occurred to facilitate its geographical spread; whether different species of Aedes mosquitoes are capable of transmitting Zika and what that may mean for future transmission; what is unique to Zika compared to other more well-known flaviviruses that can explain why it can cause congenital infections, neurological conditions and encephalitis, transmit sexually, and persist for long periods of time in multiple parts of the human body; and whether preexisting immunity to other related flaviviruses may impact Zika exposure and infection.

Some of the severe manifestations and complications associated with Zika disease include fetal loss, microcephaly, and other birth defects, and the potential for delayed mental and physical effects among infected babies born in apparent good health. These factors represent a “profound medical tragedy” and societal challenge that will require decades of financial, medical, and social support, Fauci and Morens write.

CDC investigating multistate outbreak of E. coli infections. The CDC, several states, and the FDA are investigating a multistate outbreak of Shiga toxin-producing E. coli O157:H7 infections (STEC O157:H7) in 13 states. As of last month, at least seventeen illnesses have been reported from: CA, CT, IL, IN, MI, NE, NH, NY, OH, PA, VA, VT, and WA.

Illnesses started on dates from November 15 through December 8, 2017. The Public Health Agency of Canada also is investigating an outbreak of STEC O157:H7 infections in several provinces.

Whole genome sequencing is being performed on samples of bacteria making people sick in the U.S. to provide information about whether the illnesses in the U.S. are related to those in Canada. Preliminary results show that the types of E. coli making people sick in both countries are closely related genetically, meaning that the ill people are more likely to share a common source of infection.

The Canadian health agency has identified romaine lettuce as the source of the outbreak in Canada. In the U.S., state and local public health officials are interviewing sick people to determine what they ate in the week before their illness started. The CDC is still collecting information to determine whether there is a food item in common among sick people.

Because the CDC has not yet identified a source of the infections, it is unable to recommend whether U.S. residents should avoid a particular food. The investigation is ongoing, and more information is expected to be released as it becomes available.

Industry News

ACLA sues HHS over payment-setting process. The government agency that runs the Medicare program failed to follow a congressional directive to implement a market-based lab payment system, thereby jeopardizing Medicare patients’ access to vital lab services, according to the American Clinical Laboratory Association (ACLA) in a lawsuit filed against the Acting Secretary of the U.S. Dept. of Health and Human Services (HHS) in the U.S. District Court for the District of Columbia.

The lawsuit asserts that the Centers for Medicare and Medicaid Services (CMS), operating under the purview of HHS, ignored congressional intent and instituted a highly flawed data reporting process in advance of setting market rates under PAMA. Contrary to Congress’s directives, the overwhelming majority of laboratories were prohibited from reporting private payer data. As a result, CMS failed to protect access to laboratory services for Medicare beneficiaries. This flawed process could cause serious financial harm to potentially thousands of hospital, independent, and physician office laboratories, and make it harder for Medicare beneficiaries to get access to medical testing, particularly in remote rural areas and in nursing homes that depend on laboratory testing services.

“We have repeatedly advised CMS that there are significant, substantive deficiencies in the final rule, which fails to follow the specific commands of the PAMA statute,” says Julie Khani, president of ACLA. “Contrary to Congress’s intent, instead of reforming Medicare reimbursement rates to reflect the broad scope of the laboratory market, the Secretary’s final rule will disrupt the market and prevent beneficiaries from having access to the essential laboratory services they need.”

“CMS clearly disregarded and violated the statute’s specific, unambiguous directives requiring commercial rate information to be reported and collected from a broad, diverse group of market participants,” said Mark D. Polston, partner at King & Spalding, the law firm which will represent ACLA in the suit. “Instead, information was collected from less than one percent of U.S. laboratories. More than 99 percent of labs were prohibited from reporting their data.”

ACLA representatives stressed that the organization continues to support modernizing the CLFS under PAMA, assuming the process would be based on the clear direction of Congress to establish a Medicare payment system based on the collection of private payor rates across the wide spectrum of the clinical laboratory community.

Blood Banking

Blueprint to reduce wasteful blood transfusions. After analyzing data from randomized clinical trials comparing blood transfusion approaches, experts from Johns Hopkins Medicine, Cleveland Clinic, and NYU Langone Medical Center have endorsed recommendations for blood transfusions that reduce blood use to improve patient safety and outcomes. Published in JAMA Internal Medicine, their report also provides a how-to guide for launching a patient blood management program.

As defined by existing guidelines and the clinical trials reviewed, the report reinforces these recommendations: Stable adult patients, including critically ill patients, with hemoglobin levels of 7 g/dL or higher should not be transfused; patients undergoing orthopedic or cardiac surgery, or patients with underlying heart disease with hemoglobin levels of 8 g/dL or higher, should not be transfused; and patients who are stable and not actively bleeding should be transfused with a single unit of blood and then reassessed.

The clinical trials that were examined compared so-called liberal versus restrictive blood transfusions. Liberal transfusions are those given to patients with nine to 10 grams of hemoglobin per one-tenth liter, or deciliter, of blood volume, while restrictive transfusions are those given to patients with seven to eight grams per deciliter. Many of the clinical trials examined by the researchers used the number of patients who died within a 30-to-90-day window post-transfusion as a measure of patient outcome.

Of the more than 8,000 patients included in eight clinical trials that were reviewed, there was no difference in mortality between liberal and restrictive transfusions. One trial found an increased mortality associated with liberal transfusion, and occurrence of blood clots was increased in the liberal cohort in a study that involved TBI patients.

These recommendations don’t apply to patients with acute coronary syndrome, severe thrombocytopenia, and chronic dependent anemia, including sickle cell.