Issue 82  November 23rd 2018

Canadian province solves biopsy backlog by adding staff and calling on pathologists to help with ‘gross examination’ stage of biopsy tests

Anatomic pathologist and histopathologist shortages have plagued the single-payer healthcare systems in Canada and the United Kingdom (UK) in recent years. The consequence is increased wait times for physicians in both countries to receive medical laboratory test results, which increases wait times across the entire healthcare continuum. However, one Canadian province significantly reduced a backlog that had pushed wait times for surgical pathology test results to six weeks or more. It did this by having its pathologists perform first-stage examinations normally completed by pathology assistants or medical technologists.

The Saskatchewan Health Authority (SHA) announced in October it had cleared nearly half of the 2,600-plus biopsies that were waiting to be processed at hospital labs in Regina and Saskatoon, the Regina Leader-Post reported. “I think we’ve been making amazing progress in the work,” Lenore Howey, Executive Director of Laboratory Services at SHA.

Howey stated the SHA cleared cases by having pathologists “assist with the work in the first phase”—or gross examination stage—of a biopsy. This is the part of the process during which pathology assistants or medical laboratory technologists typically record the size, weight, and description of a specimen and look for pathological changes. In addition, the SHA hired an additional pathologist assistant and three histology/cytology technologists—one on a permanent basis and two on a temporary basis.

Establishing cutoffs, reference ranges for biofluid biomarkers in Alzheimer’s disease: Reference materials and reference measurement procedures

The newly developed National Institute on Aging and Alzheimer’s Association (NIA-AA) research framework uses a biological definition of Alzheimer’s disease. This framework has increased focus on biofluid biomarkers, especially because the measurement of cerebrospinal fluid amyloid beta peptide 42 (Aβ42) (or Aβ 42/40 ratio), phosphorylated tau protein (p-tau), and total tau proteins (T-tau) are included in the definition. The field of AD biofluid biomarkers is rapidly evolving. For example, CSF neurofilament light (NfL) is associated with AD neurodegeneration and may be a better CSF marker compared with T-tau. There has also been tremendous progress in the development of plasma biomarkers (i.e. Aβ42 or Aβ 42/40 ratio, NfL, and p-tau) that are associated with AD pathophysiological processes.

There are challenges, however, in implementing these biofluid biomarkers in clinical practice. One challenge is the lack of cutoff levels and reference ranges for routine clinical use and the lack of harmonization and standardization among different methods and laboratories. The Alzheimer’s Association established an international quality control program for CSF biomarkers in 2009. This program raised awareness of method and lab differences and the lack of harmonized methods, which can be overcome through the development of reference measurement procedures, the use of certified reference materials (CRMs), and the establishment of a traceability chain.

To this end, reference measurement procedures for CSF Aβ42 and/or the Aβ 42/40 ratio were developed. The International Federation of Clinical Chemistry and Laboratory Medicine developed a working group that has produced CRMs that are commutable for CSF Aβ42 assays. Assay manufacturers can use the CRM to calibrate their assays, which should improve concordance of measurement results between different CSF Aβ42 assays and will make it possible to establish a global cutoff.

A fully human system to cultivate skin cells for grafting

Breakthrough study to culture human skin cells called keratinocytes to produce skin grafts has been published by a team of researchers from Duke-NUS Medical School and the Singapore General Hospital (SGH). This method is the first to use a specific type of tissue-proteins known as laminins, found in the human body, to create a safer treatment for severe burns or other skin-related defects.

For over four decades, skinkeratinocytes have been cultivated using a combined human-animal culturesystem. From a clinical application standpoint, this approach exposes patients to the potential risk of infections and adverse immune reactions. The animal derived products and biological agents used in the culture system are considered high-risk under a pharmaceutical standard called the Good Manufacturing Practice (GMP) system.

In this Singapore study, specific laminin proteins LN-511 or LN-421 are used as a supportive cell culture matrix and have been found to support the growth of human keratinocytes in a similar way. Lead author, Professor Karl Tryggvason, from the Cardiovascular and Metabolic Disorders Programme, Duke-NUS Medical School, who is also the Tanoto Foundation Professor in Diabetes Research, said, "Laminins have been transforming cell biology and are known to maintain stem cells and tissues architecture and function in a way that mimics the situation in the human body. The laminins play an important role in several human diseases, such as those of skin."

The method of using biologically relevant laminins in their pure forms to develop a fully human cell culture system for growing skin keratinocytes in the laboratory is a first and is likely to translate into novel treatments for many different skin disorders and wounds.

What your patients must know about direct-to-consumer lab tests

More than 12 million people have had their DNA analyzed with direct-to-consumer (DTC) genetic genealogy tests, according to estimates from the industry, with use of tests from companies such as AncestryDNA doubling in 2017. These and other DTC laboratory tests—often conducted without the involvement of a physician, with results reported directly to the patient—may lead patients to potentially harmful misunderstandings.

The AMA offers a helpful explainer on direct-to-consumer genetic testing. Results of these kinds of tests can be challenging to interpret, the AMA says. The concern is not just about DTC genetic testing, as explained in a JAMA Viewpoint article by physician-attorney Kimberly Lovett Rockwell, MD, JD. Most DTC testing companies “offer these tests widely to the public without any reference to evidence-based guidelines or the appropriateness of testing in their advertisements,” the JAMA Viewpoint says.

“Moreover, advertisements tend to entice consumers by appealing to fears of contracting common disorders such as cardiac disease, stroke and various cancers. Most of these medical tests, however, are of low or negative value for a large segment of the consuming public.” The AMA advocates modernization and reform of the oversight of clinical laboratory testing, including DTC testing.

New study sheds light on norovirus outbreaks, may help efforts to develop a vaccine

Outbreaks of norovirus in health care settings and outbreaks caused by a particular genotype of the virus are more likely to make people seriously ill, according to a new study in The Journal of Infectious Diseases. The research confirms several factors that can make norovirus outbreaks more severe and may help guide efforts to develop a vaccine to prevent this highly contagious disease.

In the new study, researchers linked, for the first time, data from a national outbreak reporting system and a laboratory surveillance network that collects data about norovirus genotypes associated with confirmed outbreaks. Their analysis, the largest of its kind, included 3,747 norovirus outbreaks affecting more than 100,000 people from 2009 to 2016. Severe outcomes, including hospitalizations and deaths, were more frequent in outbreaks caused by a specific genotype of norovirus, genogroup II type 4 (GII.4), and in outbreaks in health care settings, including hospitals, long-term care facilities, and outpatient facilities.

The findings confirm previous research about the severity of GII.4 norovirus outbreaks and suggest that future vaccines against norovirus should include these genotypes, said the lead author of the study, Rachel M. Burke, MPH, PhD, of CDC. The study results also suggest that targeting these vaccines for use in people in health care settings may help reduce hospitalizations and mortality associated with norovirus. Although there is no currently available vaccine that protects against norovirus, several candidate vaccines are in the development pipeline.

New research aims to help improve uptake of hepatitis C testing

New research published in Scientific Reports shows persisting fears about HIV infection may impact testing uptake for the hepatitis C Virus (HCV). Researchers from the University's Institute of Infection and Global Health, led by Professor Anna Geretti, piloted point-of-care testing (POCT) for a current HCV infection in an inner-city Emergency Department (ED) and assessed the influence on uptake of offering associated screening for HIV.

POCT or bedside testing is medical diagnostic testing at or near the point of care—that is, at the time and place of patient care, rather than sending a blood sample to the laboratory and then waiting for the results. Over four months, all adults attending ED with minor injuries were first invited to complete an anonymous questionnaire then, in alternating cycles, invited to take a finger-prick blood test that would either detect HCV or both HCV and HIV.

Reduced uptake: 94.8 percent (814/859) questionnaires were returned and 39.8 percent tests (324/814) were accepted, comprising 211 HCV tests and 113 HCV + HIV tests. The researchers found that offering the HCV test that was associated with a HIV test significantly reduced uptake after adjusting for age and previous HCV testing.

Professor Geretti, said: "Our study found that POCT HCV finger-prick testing was technically feasible and is suitable for rolling out to sites where people with undiagnosed hepatitis C may present so that they may [be] offered treatment… Uptake of the HCV POCT was moderate and the offer of associated HIV screening appeared to have a detrimental impact on acceptability in this low prevalence population.”

Lab samples being analyzed in Vancouver

The Yukon Hospital Corp. (YHC) began shipping routine microbiology samples to a Vancouver lab in a “phased approach” starting late last month, the Star has learned. The final decision to send lab samples down to St. Paul’s Hospital, a part of Providence Health Care, comes after several months of the hospital doing its homework to ensure that it would not negatively impact patient turnaround times, among other things, a spokesperson said this week.

It also comes after months of speculation, and anxiety expressed about the impact that outsourcing of tests could have – particularly from the Yukon Employees’ Union (YEU), as detailed in reports from last February. James Low, the YHC’s director for people services and culture, acknowledged there had been some anxiety when the option to outsource it to Vancouver was on the table, particularly about keeping care close to home and possible job losses. He maintained it was a win-win.

To be clear, though, Low assured there were also no layoffs in Whitehorse. “YHC has been able to maintain a position within the lab team for all employees affected by this change,” he wrote today. The lab had three workers before any changes were made: after the decision, two employees found a role in the hospital’s core lab that does the bulk of the other testing (amounting to the other 90 per cent), and one member will be working with the lab information systems more closely.

There were efforts to put some of these concerns to bed over the months-long consultation with lab workers and community partners like transportation providers, he added. “We needed to study it further, and we also needed to test some processes to ensure there would be no negative impact on turnaround times,” he said.