By the Numbers: Injuries and Exposures in the Lab

Finding information about the number of Laboratory Acquired Infections (LAIs) and other laboratory injuries in the United States is difficult. Many events are not reported, and of those that are reported at the facility level, only some are required to be reported to national agencies. A report by the CDC cites four studies that collectively identified 4,079 LAIs resulting in 168 deaths occurring between 1930 and 1978. Again, those are just the reported occurrences, and the data says nothing about other injuries in the lab such as slips, trips, and falls, or lacerations.

The Bureau of Labor Statistics (BLS) provides benchmark injury and exposure data for clinical laboratories, but this information too, is limited to that which is reported. That said, the information may still be of value—it can be used to compare your lab’s reportable injury data to labs across the nation. This can provide one form of assessing your overall lab safety.

The BLS provides annual clinical lab workplace injury data in the form of a rate. That rate is obtained via a calculation:

(Number of injuries and illnesses X 200,000) / Employee hours worked = Incidence rate

Incidence rates can be used to show a relative level of injuries and illnesses among different industries and within the same industry. Because a common base and a specific period of time are involved, these rates can help determine both problem areas and progress in preventing work-related injuries and illnesses. In this equation, the number of injuries and illnesses comes from your log of work-related incidents reported on your department’s OSHA 300 log. The worked hours from your lab should not include any non-work time (even if it is paid) such as vacation, sick leave, or holidays. You can estimate the worked hours on the basis of scheduled hours or eight hours per workday. The 200,000 is a constant—it represents the equivalent of 100 employees working 40 hours per week, 50 weeks per year, and provides the standard base for the incidence rates.

It takes time for national annual injury and illness rates to be calculated, so the most recent data from the BLS today is from the year 2018. Back in 2014 the rate for clinical labs was 3.4, and in 2015 it went down to 3.3. In fact, the BLS lab data shows a steady decline in reported incidents over the past twelve years. The most recent rate is 3.1. That’s good news that could mean that lab safety awareness is improving across the country.

How does your laboratory data compare to national numbers? It’s a good idea to use the calculation so that you can see how your lab is doing. If your injury, exposure and illness numbers are on the rise, it’s time to take action. Look for the causes of the incidents and implement methods of prevention. If you see a pattern of the same type of incidents, you may need to execute a safety stand-down around that specific process.

Now that you can compare your reportable data to a benchmark, what about the non-reportable events in your lab? They should get attention as well. Events like closing a finger in a drawer or cutting a finger on a clean microtome blade should always be reported to lab management and the occupational health department, but they may not be required to be reported elsewhere. They still need the same follow-up in the lab, however, and as a lab safety professional, you should be an integral part of the process to engender safety success in the lab.

While there is no national data to compare to for all types of lab injuries and exposures, it is still helpful to collect the information and calculate your lab’s rate. You can keep track of that overall rate and look for trends and make improvements on all incidents in the laboratory. Be sure to promote a culture of transparency and non-punitive reporting so that all lab accidents can be documented.

Knowing how many LAIs and other injuries in laboratories are occurring across the nation is no easy task. The best place to begin is within your own lab. Collect the data and become more familiar with this indicator that can guide you to the right path to improved employee safety in the lab.

Dan Scungio, MT(ASCP), SLS, CQA (ASQ) has over 25 years experience as a certified medical technologist. Today he is the Laboratory Safety Officer for Sentara Healthcare, a system of seven hospitals and over 20 laboratories and draw sites in the Tidewater area of Virginia. He is also known as Dan the Lab Safety Man, a lab safety consultant, educator, and trainer.

Association for Molecular Pathology (AMP) – Another Valuable Membership for Technologists

This past November, I was lucky to attend the Association for Molecular Pathology (AMP) annual meeting held in Baltimore, MD. It was the 25th Anniversary of the association and it was interesting to see how it had grown over time. I went to a session moderated by members that had seen AMP in its infancy and it was remarkable to hear how the first meeting was a group of people that could fit in one of the small conference rooms, and how it had grown to offering this meeting for hundreds of people from all around the world. They have been on the forefront of the field of Molecular Diagnostics and have worked hard for many causes affecting those in the field. They discussed important events in the history of the association, such as when AMP, along with other groups, sued Myriad Genetics, Inc, on the practice of gene patenting. Myriad had filed patents for the BRCA1 and BRCA2 genes, and thus they were the only ones who could test those genes for patients. The Supreme Court ultimately ruled that genes are products of nature, which cannot be patented, and this has led to an increase in choice for patients. This, among many other activities, is the way AMP continues to impact the field. They even had a Day of Advocacy the day before the annual meeting began when a group traveled to nearby Washington D.C. to visit with lawmakers about current issues.

If you are a technologist working in a Molecular lab, this meeting is, I believe, the most relevant one for any technologist to attend. If you are not a member of AMP, consider this a shameless plug for membership. The great thing about it is that the association really does its best to be for every one of its members. At the annual meeting, there are sidebars for each type of member, from technologist to trainees, to pathologists. I attended a lunch for trainees and technologists that included two speakers that described their journey through their different careers in the field. They were available to speak with after the session as well. I also attended an informal talk on the exhibit floor that explained the tools available for technologists through AMP, such as the technologist list serve, where I can email every technologist on the membership list for AMP if I have any questions or issues. They also described the website that guides techs to different types of certification tests and links to study guides. These were both great places to network with other technologists as well. The best thing about a technologist membership? It’s discounted compared to the pathologist membership – it’s only $75 a year and provides access to an account that has continuing education opportunities, as well as a digital subscription to the Journal of Molecular Diagnostics. Besides my membership to ASCP, I believe being an AMP member is key to staying up to date in this amazing field.

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-Sharleen Rapp, BS, MB (ASCP)CM is a Molecular Diagnostics Coordinator in the Molecular Diagnostics Laboratory at Nebraska Medicine. 

Patient Advocacy: Introduction

“I do not really understand what pathology is,” I said during my first round of interviews at ASCP. “In fact, I have a website page in front of me that describes it and I still do not really get it. I want to be upfront about that before we go any further in my interview process,” I followed. Needless to say, I got the job, but that experience really stuck with me. As I learned more and more about pathology and laboratory medicine, I was amazed that I had not known more about it. I had been to the doctor all my life, I had received some serious diagnoses, and I thought I was pretty well-versed in what my medical care entailed.

In the last few years that I have been with ASCP I have become passionate about educating patients about the role the medical laboratory plays in patient care. Without that understanding, patients will be less empowered and less likely to advocate for themselves. Their family doctors might order tests that they do not want or not order ones they that do. They might not understand certain results, which means that they are less likely to take an active role in their care. The more we education patients and their caregivers about pathology and laboratory medicine, the higher quality health care we create. Educated patients are empowered patients and it is imperative that education includes the laboratory.

Through directing the ASCP Patient Champions program, I have been fortunate to meet incredible patients, all who have some understanding of the role the laboratory played and plays in their care. Hearing them say that without the laboratory, they would only be a memory, is incredibly powerful and humbling. The active role these patients play in their care has allowed them to be more resourceful and more hopeful. For some of them, seeing their own slides has been a cathartic experience because they could suddenly see the enemy they were fighting. Others are now educating new patients about their lab tests and taking time from their own busy schedules to volunteer at hospitals and clinics.

It can also be an inspirational experience for laboratory professionals and pathologists to hear how they impacted a patient’s life. I have personally shed many tears when interviewing patients so I can only imagine what it is like to hear from someone whose life you have impacted, let alone meet them in person. It can also really help patients to have their diagnosis be explained by someone working in the lab and to understand why their blood is drawn or why a biopsy is needed.

This new series on Lablogatory called Patient Advocacy, will explore the topic of patient advocacy from laboratory professional, pathologist, and patient perspectives. Each month, you will hear how patient interactions have impacted lives and what we can do to make more people aware of the crucial role the medical laboratory plays in patient care. You are all changing and saving lives every day. Let’s learn together how we can increase our patient advocacy to help them even more.

-Lotte Mulder, EdM, is the Senior Manager of Organizational Leadership and Patient Engagement at ASCP. She earned her Masters of Education from the Harvard Graduate School of Education in 2013, where she focused on Leadership and Group Development. After she graduated, Lotte started her own consulting company focused on establishing leadership practices in organizations, creating effective organizational structures, and interpersonal coaching. She has worked in Africa, Latin America, Asia, and the U.S. on increasing leadership skills in young adults through cultural immersion, service learning and refugee issues, and cross-cultural interpretation. She is currently working toward a PhD in Organizational Leadership.

Global Health Narratives – An Interview Series Summary

2019 marked a very special year for me as I had the incredible opportunity to interview some of the most remarkable laboratory medicine specialists in the field of Pathology about their involvement in global health. Although their roles ranged from everything between medical technician, to PA, to medical student, to practicing pathologist, to the CEO of a major pathology organization, they all had one thing in common – they actively take the time to better their global community and contribute to improving pathology services in resource limited settings.

Now that the year is winding to a close, I’d like to take the opportunity to highlight all of these wonderful efforts and hopefully inspire you to take similar initiatives where applicable to your abilities and interest. Read on for a summary of each interview.

Dr. Kumarasen Cooper not only volunteers bi-annually in Botswana’s only academic pathology department as a way to give back to his native Africa, he has also worked to create an opportunity for residents at UPenn pathology to be involved too. Because of his efforts, the UPenn residents can accompany him and work together on the departments’ shared initiatives using official institutional elective time. This is a rare opportunity in pathology training, and is a model of how academic institutions can engage their trainees in global health initiatives.

Julie Papango, a medical technologist, has worked with Doctors without Borders/ Médecins Sans Frontières (MSF) to bring laboratory medicine to the world’s most remote places. She was one of MSF’s very few volunteers with laboratory experience and therefore has played a crucial role in projects ranging from addressing the infectious disease outbreaks in a Sudanese refugee camp, to helping the Cambodian Ministry of Health to improve their national tuberculosis detection program.

Dr. Ann Nelson is an expert in infectious disease pathology and has worked in many parts of Africa for more than 30 years. The focus of her work has been in HIV/AIDS pathology in the US and in sub-Saharan Africa. Currently she works on educational projects and capacity building in anatomic pathology, and linking anatomic pathology to ongoing clinical and epidemiologic research. She finds ways to be helpful in any new setting by just showing an open and willing attitude. “I went and built partnerships with everyone I could. You have to just go and talk to people, and ask them “What can we do?” With this approach, she’s been able to find countless ways to contribute her expertise to the world. She’s also spent innumerable hours in studying and publishing the issues affecting pathology services in Africa. Notably, she worked to conduct a landmark survey of African pathologists to determine the status of pathology resources in Sub-Saharan Africa.

Dr. Blair Holladay and Dr. Dan Milner have worked in global health most of their professional careers and now lead the American Society for Clinical Pathology’s efforts in improving laboratories worldwide. They are working with governments and local agencies to make sustainable changes in the neglected pathology and laboratory medicine landscape in low and middle income countries (LMICs). They are responding to the urgent need to improve pathology services to address the rapid increase in global non-communicable disease (NCD) incidence. As Dr. Holladay points out “Compared to the scale of the HIV crisis, NCDs are the health threat that gone unchecked, will go far beyond in affecting huge proportions of the global population.” In response to addressing this problem, Dr. Milner points out that the lab is the cornerstone to the solution: “In the field of cancer, which is a major problem in LMICs, you cannot treat the patient without a diagnosis – and the diagnosis must come from the laboratory.”

Dr. Constantine Kanakis is a medical student who decided to be an active part of the community of Sint Maarten while living there attending medical school. The community was facing multiple mosquito-borne infectious disease epidemics that includes Zika virus. In response, Dr. Kanakis took a service-learning elective course in medical school that focused on community outreach. He led the way to create an outreach program that has now been incorporated into the nation’s Ministry of Health Collective Prevention Services program. Dr. Kanakis encourages everyone to “Start by looking around at your immediate surroundings and take an assessment of the issues affecting the community. Anyone can do this, whether you are a physician, scientist, or a community member.”

Dr. Adebowale Adeniran, a cytopathologist, frequently works with the USCAP group “Friends of Africa” in which he speaks at the annual meetings, is involved in the group planning activities, and participates in educational initiatives and conferences in Africa. He encourages all academic institutions to engage in global health, stating “Academic institutions in the US can offer ways of enhancing training opportunities for African pathologists and trainees by offering short- or long-term exchange programs. This helps to bridge the gap between practiced based learning in resource limited vs. US institutions.”

Nichole Baker is a pathologist’s assistant that heard of a lab in Uganda that needed outside pathology help due to being severely understaffed. So Nichole decided to go visit the lab and see where she could help. One of the main issues was that the lab lacked an electronic medical record (EMR) system and keeping track of cases and patient reports was a real challenge. With no background in computer science, Nichole resourcefully reached out to her personal network to find someone that could help her build a free EMR and now the laboratory can track specimens, issue electronic reports, and has reduced their turnaround time as a result.

Dr. Drucilla Roberts is one of the world experts in perinatal pathology and has been working in Africa for over ten years with a focus on capacity building. Besides offering her surgical subspecialty expertise, she is also partnering with local pathologists to participate in ground breaking research on topics specific to low resource settings. She’s written widely on the need for pathology services in Africa. She says that one of the biggest problems in improving pathology services in Africa is that “there are not enough pathologists. You can help improve things in individual labs to a point, but for long term there has to be more pathologists working in Africa.” Dr. Roberts actively engages in solving this problem by helping train African pathology residents and by recruiting other pathologists to do the same.

Dr. Von Samedi, a cytopathologist, has worked with ASCP’s Center for Global Health at their partner sites all around the world. Dr. Samedi started working with ASCP as a resident, using his unique ability to speak French and Creole to assist ASCP in Haiti following the devastating 2010 earthquake. He has since worked on improving laboratory services in a vast array of ways, with everything from mentoring and local laboratorian training to running workshops on HIV related testing services. Volunteering gives Dr. Samedi a sense of purpose and he states that he “also benefits from interacting with my global colleagues and learning from them.”

There are so many more laboratory medicine specialists working in global health that I would have loved to feature on Lablogatory – but there are so many that I cannot capture all of their stories to share here. I hope that you have gained a snapshot of the potential ways that you can get involved, the possibilities are truly endless!

If you’ve been following this series, know that I am extremely grateful for your time and attention to this important matter. This will be my last post with Lablogatory for the time being, as I will be taking a break from writing to welcome my first child into the world! Wish me luck! J

If you want to find out more about volunteering in global pathology efforts, please visit my webpage that I have written in collaboration with Dr. Jerad Gardner: https://pathinfo.fandom.com/wiki/Global_Health_Opportunities_for_Pathologists

Please also take a moment to fill out this survey (https://www.surveymonkey.com/r/K7YK8LW) so that we can learn more about your interest and experience in global health and you can enter to win a global pathology prize pack!

-Dana Razzano, MD is a former Chief Resident in her fourth year in anatomic and clinical pathology at New York Medical College at Westchester Medical Center and will be starting her fellowship in Cytopathology at Yale University in 2020. She is passionate about global health and bringing pathology and laboratory medicine services to low and middle income countries. She was a top 5 honoree in ASCP’s Forty Under 40 in 2018 and was named to The Pathologist’s Power List of 2018 and 2019. Follow Dr. Razzano on twitter @Dr_DR_Cells.

Microbiology Case Study: A Child with Acute Abdominal Pain

Clinical presentation

An elementary school age child presented to the pediatric emergency department with an acute onset of abdominal pain. According to the parents, the patient recently had an ear infection and completed a course of amoxicillin. They noted the patient was more tired than usual, but did not have a fever. They reported no recent sick contacts or travel. Past medical history was significant for constipation, but normal bowel movements were noted over the past few days. On physical exam, the abdomen was soft and non-distended with diffuse mild tenderness noted on the right side. No masses were noted.  Laboratory testing was unremarkable and the WBC count, liver & pancreas enzymes, and alpha fetal protein were within normal limits. An abdominal CT scan revealed a mass with central necrosis in the liver concerning for an abscess. The patient was started on ceftriaxone & metronidazole and underwent a surgical procedure to drain the lesion.   

Laboratory Identification

Image 1. Gram stain of the direct liver aspirate showed many gram positive cocci in pairs & chains and numerous white blood cells (oil immersion).
Image 2. Rare small, white non-hemolytic colonies grew on CDC agar after 42 hours of incubation at 35°C under anaerobic conditions.

No bacterial growth was observed on blood or chocolate agars incubated at 35°C in CO2. MALDI-TOF mass spectrometry identified the isolate as a viridans groups streptococci, Streptococcus intermedius. The organism was susceptible to penicillin, ceftriaxone, and vancomycin by broth microdilution. Blood cultures were not collected for this patient.

Discussion

Streptococcus intermedius is a viridans group streptococci that belongs to the S. anginosus group. The S. anginosus group also includes S. anginosus and S. constellatus. This group of viridans streptococci composes the normal flora of the oropharynx, urogenital, and gastrointestinal tracts. These organisms are known for causing peritonitis and abscesses, particularly in the brain, breast, liver, and oral cavity.

Similar to other streptococci, S. intermedius is a gram positive cocci that grows in chains and is catalase negative. The anginosus group are facultative anaerobes and grow as pinpoint colonies (<0.5 mm) on blood agar. This is in contrast to pyogenic, beta-hemolytic streptococci which are greater than 0.5 mm in size after the same incubation period. The anginosus group streptococci can exhibit a variety of hemolysis patterns, including alpha, beta, or gamma hemolysis. A distinct butterscotch or caramel odor is noted on examination. The anginosus group can possess Lancefield antigens A, C, F, G, or be non-groupable, so it is important not to misidentify them as other streptococci that also have these antigens.

Historically, further identification of viridans group streptococci was challenging; however, the advent of automated systems and MALDI-TOF mass spectrometry has been useful in providing species level identifications for more common isolates. Molecular sequencing methods using sodA gene can be helpful as well for the most reliable results. While penicillin resistance is becoming more frequent in viridians group streptococci, it is still rare in the S. anginosus group.  

In the case of our patient, an echocardiogram was performed and found to be negative for endocarditis. The patient’s symptoms improved and they were discharged home on ceftriaxone and metronidazole. A follow up CT scan to confirm resolution of the abscess was scheduled.  

-Lisa Stempak, MD is the System Director of Clinical Pathology at University Hospitals Cleveland Medical Center in Cleveland, Ohio. She is certified by the American Board of Pathology in Anatomic and Clinical Pathology as well as Medical Microbiology. Her interests include infectious disease histology, process and quality improvement, and resident education.

Is it Christmas? Hematology Case Study: Coagulopathy

A 2 year old male was brought into the pediatrician’s office by his mother after tripping over a toy truck 2 days earlier. The mother stated that the child cut the inside of his lip in the fall, and the lip had been oozing blood for the past 2 days. The child had also experienced a bloody nose several times since the fall. Upon examination, the child appeared in general good health with no other bruising or bleeding. Examination of the joints revealed swelling in the right knee. The physician took a family history, and the mother reported that her younger brother has ‘some sort of bleeding problem’ and experienced prolonged bleeding after a tonsillectomy as a child, and after several surgeries as a young adult. The physician ordered blood work on the child.

  • Hgb 9.5 g/dl
  • Hct 30%
  • Platelet  185 x 103/ uL
  • INR  1.1
  • aPTT 57 sec
  • Mixing Test: corrected
  • Thrombin Time: normal

Based on these results, the prolonged aPTT warranted further investigation. A differential diagnosis involved ruling out other causes for the prolonged aPTT. The physician ordered mixing studies, factor VIII and factor IX assays and vWF. Mixing studies are used to determine if etiology of prolonged PT or PTT is due to a factor deficiency or an inhibitor. If the aPTT remains prolonged after mixing with normal plasma, this indicates an inhibitor. If the prolonged PTT becomes normal after the mixing studies, this would indicate a factor deficiency. The factor VIII and vWF were normal, but factor IX activity was 25%. Diagnosis: Factor IX deficiency. (It was also confirmed, after speaking with the child’s uncle, that he also had a factor IX deficiency)

So, you may ask, what does this have to do with Christmas? In the spirit of the season, I chose to present a Case Study on Factor IX deficiency, aka Christmas Disease. But, alas, this really has nothing to do with the holiday. Maybe it has something to do with the fact that the first article about this disorder was published in the British Medical Journal on Dec 27, 1954 (just 2 days after Christmas)? But, not so. Actually, Factor IX deficiency is also called Christmas Disease because it is named after Stephen Christmas, the first patient described to have Factor IX deficiency. Stephen Christmas was diagnosed with hemophilia in Toronto in 1949, at the age of 2. The family was visiting relatives in London in 1952 and it was there that doctors discovered that he was not deficient in Factor VIII, the cause of Classic Hemophilia as it was known at the time. It was discovered that he was deficient in another coagulation protein. This new protein was named Christmas protein and later became known as Factor IX.

A little bit more about the history of Factor IX deficiency. Before the discovery of the Christmas protein, it was thought that Hemophilia was a single disorder, caused by a deficiency of Factor VIII. With the discovery of this new protein, Classic Hemophilia (Factor VIII deficiency), was given the name Hemophilia A, and this new Factor IX deficiency became known as Hemophilia B. Yet another nickname for this disorder is the Royal Disease. Hemophilia was prominent in the European royal families in the 19rth and 20th centuries. Queen Victoria of Britain was a carrier of hemophilia and passed the gene on to three of her children. Her children and descendants married into the royal families of Germany, Russia and Spain, giving her the nickname the Grandmother of Europe. But, these marriages also served to spread the disease to these other royal houses, giving hemophilia the nickname Queen Victoria’s curse. The last known member of the royal families of Europe to carry the gene passed away in 1945, 9 years before that article in the British Medical Journal (December 27, 1954). So, how do we know that Hemophilia B is the hemophilia responsible for the Royal Disease? In 2009, DNA testing on bones identified as  Anastasia and Alexei Romanov, the last Russian royal family descendants of Queen Victoria, determined that the Royal Disease was Hemophilia B.

I remember teaching Hematology and Genetics before 2009 using a pedigree chart of Queen Victoria’s family to teach students about Hemophilia as an X linked recessive disorder. We created Punnett squares that showed the inheritance from Queen Victoria to her family members and descendants across Europe. I always enjoyed this lecture, because it was a fun piece of historical trivia paired with a good science lesson. After 2009, the science of the inheritance did not change, but we now knew that this Royal Disease was Hemophilia B. Hemophilia B is caused by mutations in the F9 gene which is responsible for making the factor IX protein.  The F9 gene is on the X chromosome. Hemophilia B, like Hemophilia A, is X linked, carried by the mother. 50% of males born to a carrier mother will have the disease and 50% of daughters will be carriers. All daughters of affected males will be carriers, but their sons will not be affected. Hemophilia A is more common than Hemophilia B, affecting about one in 5,000 males. Hemophilia B affects about one in 25,000 males. It has been though that up to about 30% of Hemophilia B cases occur as a spontaneous mutation and are not inherited. This has been thought to be the case with Queen Victoria. She has been believed to be ‘case zero’, the first hemophilia case in her family. However, some newer articles that have researched her family history suggest that she may have had a half-brother who had the disease.1 There are also other related disorders including a rare autoimmune acquired hemophilia B and another rare form of Hemophilia B called Hemophilia B Leyden.

The coagulation process involves many chemical reactions, from the initial event that triggers bleeding, to the formation of a clot. The sequence of events are generally depicted as a coagulation cascade to illustrate and simplify understanding of the process. The coagulation cascade is divided into 2 pathways, the intrinsic and extrinsic system, and a common pathway. This segregation of sections is not physiological, but allows for the grouping of factor defects and the interpretation of laboratory testing. Most problems with coagulation factors fall into one of three categories: a factor is not produced, there is a decreased production, or the factor is produced but not functioning properly. Hemophilia B is a factor IX deficiency. It is classified as mild, moderate or severe based upon the activity level of factor IX. In mild cases, bleeding symptoms may occur only after surgery or trauma and may not be diagnosed until later in life. In moderate and severe cases, bleeding symptoms may occur after a minor injury or even spontaneously. These moderate to severe cases are usually diagnosed at a younger age.

This child was diagnosed with Hemophilia B, based on coagulation studies, Factor IX assay results and family history. Treatment involves replacement of Factor IX to promote adequate blood clotting and prevent bleeding episodes.

References

  1. Turgeon, Mary Louise, Clinical Hematology: Theory & Procedures, 6th ed.  Lippincott Williams and Wilkins, Philadelphia, 2017.
  2. https://www.hog.org/publications/detail/the-royal-disease-a-family-history-update-on-queen-victoria
  3. https://rarediseases.org/rare-diseases/hemophilia-b/
  4. https://pediatriceducation.org/2015/12/14/what-is-it-called-christmas-disease/
  5. https://www.stago-us.com/hemostasis/tests-clinical-applications/hemophilia-b/

-Becky Socha, MS, MLS(ASCP)CM BB CM graduated from Merrimack College in N. Andover, Massachusetts with a BS in Medical Technology and completed her MS in Clinical Laboratory Sciences at the University of Massachusetts, Lowell. She has worked as a Medical Technologist for over 30 years. She’s worked in all areas of the clinical laboratory, but has a special interest in Hematology and Blood Banking. When she’s not busy being a mad scientist, she can be found outside riding her bicycle.

Recognizing Disruptive Innovation in Global Health

One of the challenges of providing healthcare to patients of any type is “staying current” or “keeping up with the literature.” This can be especially challenging in the diagnostics laboratory where novel or unique approaches to a given test or test method or disease may show early promise but have no clinical utility, be too expensive, or not actually significantly change work-flow and/or patient value to justify implementation. On the other hand, sometimes a technology or test which is in development or approval can be so anticipated that clinicians and laboratorians are frustrated that it is not yet available.

In global health, there is a different problem that is encountered every day. There are technologies and tests that are approved, have documented clinical utility, and add great value to patients but they are simply not available because of supply chain, cost, administration, or geography. In such situations, the practitioners in these settings face extreme frustration—especially with stock-outs—and can become jaded and non-dependent on laboratory testing as part of care. This latter issue is a major challenge in cancer care where cancer diagnoses are required before treatment can begin; yet, in a large number of countries, access to cancer diagnostics routinely is not available. It is to that end that ASCP along with a whole host of NGO, industry, academic, and government partners are making great efforts to improve cancer care in each part of the continuum.

In this environment, however, disruptive innovations are, in fact, much easier to recognize as forthcoming. In the early 2000’s when I was working and traveling in Malawi, our project had a landline in the hospital to call the landline at the doctor’s house for issues overnight with patients. This required 24-hour nurses to be physically in the ward, tied to the phone and the patients. Landlines were expensive to install, had a very long waiting list to be installed, and, for the most part, the majority of the population in the country had never had a phone line in their dwelling. By the mid-2000’s, our project had one or more cellphones (as did the nurses) and communications through texting were nearly constant (especially since it was less expensive than making a phone call). By 2010, cell phones were ubiquitous in Malawi (and almost everywhere else in Africa) and there was no demand for landlines. Although this is a commonly used example, consider the adoption of cellular telephones and now smartphones in the US compared with Africa. There was push back, denial, avoidance, and even refusal to use them because there was an existing, well established system of landline communication.  If you want to install cable television and internet in your home as late as 2016, you were often required to bundle with a landline. The point is that the adoption pattern was significantly different because there was a pre-existing competitor with the new technology although—clearly—the new technology was superior.

Now consider a woman of 35 years who has a breast mass on mammogram in downtown Boston today. She will likely have an imaging study with immediate ultrasound and fine needle aspiration and/or core biopsy subsequent. A pathological diagnosis will be issued within 3 to 4 business days (or sooner) which includes a histological diagnosis along with hormone receptor status and Her2 staining. She will see a clinician likely within a week for a positive cancer diagnosis and a treatment plan will be decided upon and executed. If we consider a similar woman in downtown Nairobi, Kampala, or Lagos, they may, in fact, have a similar experience because of the recent efforts globally to improve cancer awareness, diagnosis, and treatment. There may be some delays (reports may take several weeks), potential stock-outs, etc. but, in these major cities, the services might exist. They are likely, however, provided in private clinics, will cost a premium, and may or may not have any guarantees about quality.

The reality, however, is that the vast majority of women in the US or Europe who present with breast cancer do so at a very early stage because of active screening programs which include mammography. The vast majority of women in low- and middle-income countries (LMICs) present with later staged disease because of lack of screening. The latter group of women, however, often live in rural conditions and/or poverty conditions such that seeking care for a breast mass (of any size) will require them to spend time and money to travel to one of the major cities and attempt to access services. With this situation, many of these cancers are detected by the health system at a late stage where curative therapy windows have been missed.

Onto these observations let’s now overlay access to a test for a breast mass that can be performed on a fine needle aspiration biopsy and resulted in ~4 hours which will provide a diagnosis of cancer (or benign) along with prognostic features directing treatment. If we consider the woman in Boston, we may see such a test providing an incremental improvement in care because billing systems, litigation fears, compliance requirements, or accreditation standards still include routine histology and immunohistochemistry to be performed on a tissue biopsy. To some degree, the test may be rejected because it is adding a cost over the standard costs without adding value (other than speed) to the results. However, for the woman in the rural village who likely has access to a community health worker, access to such a test could mean that she starts oral therapy the same day she has the health visit without ever having to leave her village. We have now removed the journey to a clinic that can performed a biopsy, the costs associated with that travel, the time lost while traveling and waiting for a result, and removed the risk that this is not breast cancer—which would mean all the time and money were wasted. For this woman, enormous value is created for her with a test that is performed same day with immediate results.

This concept of point-of-care (POC) cancer diagnostics would arguable meet resistance in the US or European system because of competition with existing systems and other issues as mentioned previously. In an LMIC setting, as there may be no competition, such an innovation would sweep the system and become standard of care—almost regardless of cost. This last bit is very important because traditional systems for performing histology and IHC are complex, costly, and require multiple highly trained individuals to get a quality result. If that process costs $75 to $100 US dollars (to the health system) to provide and, for the individual patient, $10s to $100s of dollar for the travel, lodging, and lost wages, the cost of such a test could, in a stable, high-income country (HIC) market, fetch a hefty price. However, if such a test is priced at $25 to $50 USD (half the cost of the current system excluding the travel), the immediate replacement of the old system with this new system for the given indication must and will occur. This uptake is amplified in an LMIC when the POC test moves to the patient in a geographically distributed process. Breast cancer is an obvious target for such an approach because the tumors are easily accessible, the disease is quite common globally, and the primary therapies are very inexpensive. Could such a test have an impact in an LMICs for bone marrow-based, lung, bladder, colon, prostate, liver, kidney, or soft tissue tumors? The answer to that question lies in the availability of therapy, incidence of disease, and access to radiological equipment rather than availability of the actual POC device. That is, once you have a POC test for one cancer, creating a subsequent POC test for another cancer is a surmountable technical hurdle. But will such a test be able to have an impact because of the alignment of the other factors? It is likely that as you are reading this sentence, you have thought of a few yourself but there are certain cancers where you are likely thinking, “not possible”.

For breast cancer, two such POC approaches are coming down the pipeline. The first is the Cepheid GeneXpert Breast STRAT4 assay which measures quantitative RNA (qRNA) for ESR1, PGR, ERBB2, and MKi67. These four assays are surrogates for standard immunohistochemical staining for ER, PR, Her2, and Ki-67, respectively. In a series of published and in press feasibility and validation studies, the qRNA assay is essentially equivalent to IHC. There are nearly a dozen studies of this new testing cartridge using formalin-fixed, paraffin embedded (FFPE) tissue throughout Africa where the test is being compared to standard IHC. However, in at least one site, the test is being performed directly on FNA material. The second test is from the laboratory of Dr. Sara Sukumar at Johns Hopkins which uses a set of DNA methylation markers that can separate benign from malignant disease on FNA using only 10 markers. By combining these two approaches (benign vs. malignant followed by STRAT4 for positive tumors), a diagnosis of malignant breast disease with prognostic factors for treatment could be obtained in less than 4 hours.

Let’s jump forward to the point in time when both of these POCs are available (or, in fact, any POC for cancer is available). How would they change the approach to breast or other cancer in an LMIC? Because both tests require only an FNA of a mass and because tumors of the breast and other organs today are often late staged, community health workers could be trained to evaluate patients with masses, perform the sampling, and run the test in a remote village. Regardless of stage, starting a breast cancer patient on estrogen receptor antagonists can provide palliative relief or pre-surgical treatment. As a population down stages—which occurs as community health workers begin routine screening—the testing can triage benign and malignant disease at a fraction of the cost for both the system and the patient. Based on population epidemiology, nearly exact costs for these services can be predicted for a population and stock outs can be avoided. Corollary note: Only for those cancers for which you HAVE a POC.

How would these tests change the approach to breast cancer in an HIC? There would likely be resistance at many levels but, eventually, the relatively low cost and the increased patient value would allow the tests to replace or displace standard diagnostics. Without complete replacement, there could, at a minimum, be multimodality redundancy which increases quality. However, the tests would find purchase within the system because in some settings their cost and added value would make any other choice impossible.

For both settings, we can now add other market entrants, other tests for other cancers, and a generalize increased in cancer awareness in the community, all of which would increase demand, improve morbidity and mortality, but decrease costs. Such a situation would be highly valued by the patients and, therefore, is the most important eventuality as this disruption ensues. Recognizing forthcoming change is sometimes hard and sometimes easy; however, accepting and embracing forthcoming change in healthcare can lead to best outcomes for our patients—the central mission of ASCP.

Dr. Milner has no financial disclosures regarding this blog post and has received no fiscal or in-kind support from any entity, named or otherwise, that involves this blog post.

References

  1. Wu NC, Wong W, Ho KE, Chu VC, Rizo A, Davenport S, Kelly D, Makar R, Jassem J, Duchnowska R, Biernat W, Radecka B, Fujita T, Klein JL, Stonecypher M, Ohta S, Juhl H, Weidler JM, Bates M, Press MF. Comparison of central laboratory assessments of ER, PR, HER2, and Ki67 by IHC/FISH and the corresponding mRNAs (ESR1, PGR, ERBB2, and MKi67) by RT-qPCR on an automated, broadly deployed diagnostic platform. Breast Cancer Res Treat. 2018 Nov;172(2):327-338.
  2. Wasserman BE, Carvajal-Hausdorf DE, Ho K, Wong W, Wu N, Chu VC, Lai EW, Weidler JM, Bates M, Neumeister V, Rimm DL. High concordance of a closed-system, RT-qPCR breast cancer assay for HER2 mRNA, compared to clinically determined immunohistochemistry, fluorescence in situ hybridization, and quantitative immunofluorescence. Lab Invest. 2017 Dec;97(12):1521-1526.
  3. Downs BM, Mercado-Rodriguez C, Cimino-Mathews A, Chen C, Yuan JP, Van Den Berg E, Cope LM, Schmitt F, Tse GM, Ali SZ, Meir-Levi D, Sood R, Li J, Richardson AL,  Mosunjac MB, Rizzo M, Tulac S, Kocmond KJ, de Guzman T, Lai EW, Rhees B, Bates M, Wolff AC, Gabrielson E, Harvey SC, Umbricht CB, Visvanathan K, Fackler MJ, Sukumar S. DNA Methylation Markers for Breast Cancer Detection in the Developing  World. Clin Cancer Res. 2019 Nov 1;25(21):6357-6367.

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-Dan Milner, MD, MSc, spent 10 years at Harvard where he taught pathology, microbiology, and infectious disease. He began working in Africa in 1997 as a medical student and has built an international reputation as an expert in cerebral malaria. In his current role as Chief Medical officer of ASCP, he leads all PEPFAR activities as well as the Partners for Cancer Diagnosis and Treatment in Africa Initiative.