A COVID Reflection

Usually, I talk about some of the more administrative happenings in the laboratory world (accreditation, competency, etc.). Today, however, as there is seemingly a glimmer of light at the end of the nation’s pandemic tunnel, I thought I would reflect on what we have collectively experienced.

 Like much of the nation, it has been a difficult journey for laboratorians. It has been particularly trying for those who were asked, who were required, to rise up and meet the unprecedented challenges of the times while suffering from the same burdens of fear, uncertainty, and physical ailments as those they were serving.

Dying Alone

One year ago, my uncle died from COVID-19. He died alone and afraid in the nursing home where he never wanted to be. We visited him after being given special permission from the president of the company operating the nursing home. After being told about how unusual it was to be allowed to see him, we dressed in full PPEs and went into his room. We found him curled in a fetal position, dead and cold to the touch. It was so unfair.

I think about all of the laboratorians who had to endure similar or worst experiences: those who lost close family members and even those who themselves suffered through the disease.

Unseen Warriors

Laboratorians have always been the silent warriors in the life-long battle to defeat pain and disease. More often, nurses and doctors received public gifts of admiration and praise for their service to patients. With quiet satisfaction, laboratory technologists, technicians, and support personnel are dedicated 24 hours a day, seven days a week, to providing the information on which 70% of medical decisions are based. Information that no other group of professionals can provide.

I think about all of the effort and skill required in the mad rush to set up tents and collection sites needed across the nation. And then, too, there were the laboratories needing to scale up testing or create entirely new testing areas with new instruments and new tests kits. The chaos was magnified by constantly changing guidelines, reagent shortages, and a lack of trained personnel.

Amid all the confusion, misinformation, and anger, laboratorians were themselves experiencing disease, death, and social isolation. Yet still, they delivered the results the nation needed to understand the pandemic’s depth and breadth.

Needless Death

Now the Delta variant has taken hold just when the nation thought the disease, if not bested, had at least been brought under some semblance of control. Unfortunately, the refusal of many to get vaccinated contributes to the virus’s persistence. More will suffer, and more will die.

How many needless deaths will the nation have to experience? Will there ever be a point when everyone who can be vaccinated will be? Or, two years later, will we be mourning preventable COVID-19 deaths. Will we still have to watch our loved ones perish with a tube down their throat, or worst, alone in a room far away surrounded by cold walls and quiet indifference?

 Sigh.

Regardless of where this pandemic leads or how the nation reacts, laboratorians will continue to remain steadfast in their dedication to their profession and their patients. We have often considered ourselves the stepchild of the healthcare industry because, despite the criticality of what we do, we go unnoticed and unremarked on as long as we deliver the results our patients need. We are okay with that.

We are also tired and worn.

Conclusion

Thanks, fellow laboratorian, for reading this minor soliloquy of frustration and sadness. I will probably be back next quarter discussing inspections, competency, or some other administrative aspect of laboratory operations. I hope, also, to discuss how the nation has reached or is close to reaching the theoretical goal of herd immunity because of high vaccination levels. However, if I were honest, I know the likelihood of this happening is disappointingly low.

If you can get vaccinated, please do.

-Darryl Elzie, PsyD, MHA, MT(ASCP), CQA(ASQ), has been an ASCP Medical Technologist for over 30 years and has been performing CAP inspections for 15+ years. Dr. Elzie provides laboratory quality oversight for four hospitals, one ambulatory care center, and supports laboratory quality initiatives throughout the Sentara Healthcare system.

Pitfalls of Artificial Intelligence for COVID-19 Variant Classification

While you have surely heard about all of the SARS-CoV-2 variants and how concerning they are, I would bet that you may not know how they are classified. Sure, from my last post, the technical aspects of whole genome sequencing and targeted approaches have been described, but bioinformatic (big data) analyses are essential to assign lineages. Furthermore, the advances of machine learning have been integrated into this system for SARS-CoV-2 lineage assignment.

How VOC lineages are given

First, phylogenetic trees (circular example below) are formed to demonstrate relatedness of strains based on how many mutations they share. The more similar they are, the closer they are together. These trees are not new nor do they rely on artificial intelligence, but they can give visual clues as to whether a lineage is new.  For instance, when the first variant of concern B.1.1.7 (now called Alpha) was discovered, it branched away from other limbs of the phylogenetic tree.

Within these new viral variants, there are a set of mutations that are present in most of the viral variants. For instance, there are 17 protein coding changes in Alpha variant. However, these exact 17 mutations may not be in every Alpha variant. Individually, mutations may be present in 98% of isolates or lower; the spike gene deletion of amino acids 242-244 of the Beta variant (B.1.351, South Africa origin) is only present in 88% of specimens sequenced. This could be due to issues in sequencing, data processing, or just the prevalance/biology of the virus.

As there are many mutations that fit into certain variants, it would be difficult for a human to process all of this information in a probabilistic manner to assign lineages. Thus, machine learning tools (most common SARS-CoV-2 program is Pangolin) have been added onto the end of bioinformatic analyses to assign the lineage to a sample.

How machine learning works

The subject of machine learning has been discussed in a previous post about Protein folding prediction. Briefly, it is helpful to remember that machine learning is a process to create algorithms that give an outcome based on training data. The more diverse, large, and well curated the data, the better the accuracy of the program. One pitfall is they are based on previous data, which works well for many situations: using AI to find a lung cancer on chest x-ray would work well, because lung cancers have consistent characteristics.

However, with COVID-19, new variants keep arising and current variants are evolving (think Delta and Delta “plus”). Furthermore, if the classifier Pangolin is trained on high quality data, then trying to interpret lower quality data (missing genome regions, few sequencing reads) may confuse Pangolin and lead to inaccurate results. What follows is an example of how this occurred at our institution.

Case study

We have been sequencing COVID-19 positive specimens at UT Southwestern for the last several months. Many of the cases have been the Alpha variant (B.1.1.7, origin U.K.). However, it was around this time that Delta (B.1.617.2, origin India) cases started to arise. In one week, we found two specimens that were classified as B.1.95. This was an unusual variant I had not heard of before. There are several “wild type” strains that are B.1.1/ B.1.2 and other derivations, but I had not seen anything like this before.

Clinical history

Two specimens sequenced belonging to Hispanic, adolescent brothers whose mother had recently been hospitalized with COVID-19. There was information on mother’s travel history.

Therefore, I performed manual review of the specific variants. Many of the diverse mutations occur in the spike protein, so this was analyzed first. Immediately, I noticed two classic mutations of the Delta variant: a 2 amino acid deletion in the spike gene (S:Del157_158) and a receptor binding site mutation (S:L452R) also seen in the variant from California (B.1.429). Other mutations could be evaluated, but the combination of these two mutations is unique to Delta variant.

One suspected cause was that the Pangolin lineage classifier had an issue. Specifically, it had not been updated since February 2021- when Delta did not exist. Thus, there was no data for the program to classify the variant properly. Upgrading to the latest version of Pangolin provided the correct lineage classification.

A Few weeks later…

Once again, I was checking the lineages reported by the classifier and there were several B.1.617.2 and B.1.617.1. Both of these are variants from India (before the helpful WHO Delta designation), but they are distinct sub-variants. It was odd to see B.1.617.1, because this was found to be less infectious compared to the dominant B.1.617.2 variant (later named Delta) and B.1.617.1 was not spreading across the globe.

Intervention:

Therefore, I once again went to the sequence data for the spike protein to compare some mutations. Although these are sub-variants from the same original variant, they have several mutually exclusive mutations in the spike protein. The figure below compares the prevalence of specific mutations in the spike protein of B.1.617.1 and B.1.617.2 (dark purple = common in a variant, white = rare).

Upon manual review, all of the spike gene mutations were specific to B.1.617.2. So why was there an issue in classification? Again, there were few sequences for either of these sub-variants at that time, so the classifier wasn’t as well trained. Updating the Pangolin version brought the benefit of new data and more accurate classifications.

Take away messages

  1. Updating Lineage classification software (Pangolin) on a regular basis is needed for accurate results.
  2. Manual review is essential for any abnormal findings- a typical process for pathologists, but also plays an important role in COVID-19 variant monitoring.
  3. Know what you’re looking for and know which mutations differentiate the variants.
  4. Delta is now the dominant strain in the U.S. (graphic below).

References

  1. Outbreak.info
  2. https://pangolin.cog-uk.io/

Jeff SoRelle, MD is Assistant Instructor of Pathology at the University of Texas Southwestern Medical Center in Dallas, TX working in the Next Generation Sequencing lab. His clinical research interests include understanding how lab medicine impacts transgender healthcare and improving genetic variant interpretation. Follow him on Twitter @Jeff_SoRelle.

Microbiology Case Study: 70 Year Old Man with a History of Papillary Urothelial Carcinoma

Case Description

A 70 year old male with a past medical history of hypertension and non-invasive multifocal high grade papillary urothelial carcinoma was being followed closely for recurrence and underwent magnetic resonance imaging (MRI) of the abdomen and pelvis. The report described a 2.6 x 3.9 x 5.2 cm lobulated cystic mass involving the left psoas muscle. Furthermore, there was encasement of the left common iliac artery and less involvement of the left common iliac vein (Image 1). Further evaluation of the lesion was pursued to determine the etiology. An important aspect of this case to consider is the patient’s prior cancer treatment regimen, which included intravesical Bacille Calmette-Guerin (BCG) for 5/6 cycles. The final BCG treatment was held because the patient developed “BCG-osis” comprised of chest pain, rigors, chills and hypotension. Given the only pathology to date on the patient was non-invasive papillary carcinoma (even though it is high grade), the oncology group did not think the psoas muscle lesion was a metastasis. Fine needle aspiration (FNA) was pursued and the CT-guided aspiration demonstrated “abundant histiocytes and acute inflammation with necrotic debris…Acid fast organisms identified on AFB (acid fast bacilli) stain…Negative for malignant cells” (Image 2). Microbiology cultures were obtained at the time of FNA. The AFB smear showed 1+ AFB. AFB grew in culture and reacted with the Mycobacterium tuberculosis complex probe. The patient’s interferon gamma response assay (IGRA) was negative the year prior. Antimicrobial susceptibilities (AST) using the Mycobacterial Growth Indicator Tube system with single drug concentrations revealed susceptibility to isoniazid, rifampin, and ethambutol with resistance to pyrazinamide. Per protocol, the isolate was sent to a reference laboratory for identification which returned as BCG. During the interim, before AST was available, the patient was referred to our Infectious Diseases outpatient clinic where he was started on R(ifampin)-I(soniazid)-P(yrazinamide)-E(thambutol) therapy and then followed up his care with the county health department.  

Image 1. Magnetic resonance imaging of the pelvis demonstrating an enhancing multilobulated cystic mass overlying the left psoas muscle Top: transverse plane (orange arrow). Bottom: sagittal plane (orange arrow).
Image 2. Photomicrographs of the drained fluid from the psoas muscle abscess.
Top) hematoxylin and eosin photomicrograph demonstrating abundant neutrophils and necrotic debris (10x objective).
Bottom) AFB stain demonstrating multiple AFB (see arrows) within the necrotic cellular debris (50x oil immersion objective).

Discussion

BCG is an attenuated strain of Mycobacterium bovis that has, historically, been used as a vaccine to Mycobacterium tuberculosis (MTB) most often used in areas of endemicity. M. bovis is a member of the MTB complex so hybridization probes used in clinical laboratories can distinguish MTB complex from Mycobacterium kansasii or Mycobacterium avium complex but cannot distinguish the MTB complex members from one another. Reference laboratories have molecular techniques including PCR or sequencing that can separate the differing members of the MTB complex. Another traditional distinguishing characteristic between M. bovis (including BCG) and MTB is susceptibility to pyrazinamide. MTB carries a pyrazinamidase which is required to activate the antibiotic; M. bovis does not, so it is intrinsically resistant to pyrazinamide. A laboratorian or clinician should be cognizant of this when a culture result returns as MTB complex that is susceptible to rifampin, ethambutol and isoniazid but is resistant to pyrazinamide alone. Furthermore, IGRAs were designed, in part, to distinguish those who have been vaccinated with BCG versus those exposed to MTB or wild type M. bovis who are latently infected. IGRAs will be negative in those exposed to BCG but would be reactive with either MTB exposure or M. bovis (non-BCG strains).

This case describes an uncommon complication of BCG immunomodulator therapy as a treatment of superficial papillary urothelial carcinoma. BCG’s use as a therapeutic intervention for malignancy is unique. It is postulated that the instillation of the organism stimulates the host’s immune response which can cause inflammation and sloughing of the bladder lining (urothelial cells), which effectively removes foci of superficial pre-cancerous in situ lesions or other intact foci of superficial urothelial carcinoma. The typical course of treatment is 6 cycles of BCG. Local inflammation resulting in cystitis is the most common complication experienced in 27-95% of patients.1 However, approximately 19% of patients undergoing BCG therapy experience severe enough complications to prematurely terminate BCG therapy, according to one study by the European Organization for Research and Treatment of Cancer.2 The patient described developed systemic symptoms during the course of his BCG therapy which prompted his physicians to terminate it. Although far less common than local genitourinary symptoms, mycotic aneurysms can occur in an estimated 0.7-1.4% of cases.1 Psoas abscesses are thought to arise from mycotic aneurysm leak.3

References

  1. Liu Y, Lu J, Huang Y, Ma L. Clinical spectrum of complications induced by intravesical immunotherapy of bacillus Calmette-Guerin for bladder cancer. Journal of Oncology. 2019. DOI: 10.1155/2019/6230409
  2. Sylvester, R, Brausi M, Kirkels W, et al. Long-term efficacy results of EORTC genito-urinary group randomized phase 3 study 30911 comparing intravesical instillations of epirubicin, bacillus Calmette-Guerin, and bacillus Calmette-Guerin plus isoniazid in patients with intermediate- and high-risk stage Ta T1 urothelial carcinoma of the bladder. European Urology. 2010. 57:5; 766-773.
  3. Leo E, Molinari A, Rossi G, et al. Mycotic abdominal aneurysms due to Mycobacterium bovis after intravesical bacillus Calmette-Guerin therapy. Annals of Vascular Surgery. 2015. 29:6;1381.e1-1318.e6.

-Dominick Cavuoti is a Professor at UT Southwestern Medical Center who specializes in Cytopathology, Infectious Disease pathology and is a medical director of the Microbiology laboratory at Parkland Health and Hospital System.

-Kelley Carrick is a Professor at UT Southwestern Medical Center who specializes in Cytopathology and Gynecologic pathology. She is the Chief of Cytopathology at Parkland Health and Hospital System.

-Clare McCormick-Baw, MD, PhD is an Assistant Professor of Clinical Microbiology at UT Southwestern in Dallas, Texas. She has a passion for teaching about laboratory medicine in general and the best uses of the microbiology lab in particular.

Microbiology Case Study: Salads, Stool, and Special Staining Studies

Case History

A woman in her 40s presented to her primary care physician in summer 2020 with mild abdominal pain, diarrhea, nausea, and headache. She experienced loose bowel movements 3 – 4 times per day for the past 18 days. She denied bloody stools, travel, consumption of raw or undercooked meats or unpasteurized dairy, contact with animals, or recent antibiotic use. SARS-CoV-2 PCR was negative. A stool sample was collected and sent for an enteric panel PCR (Salmonella, Shigella, Campylobacter, and Shiga toxin), a bacterial stool culture (Aeromonas, Plesiomonas, and Vibrio), and an ova and parasite (O&P) exam with a request to perform a modified acid-fast stain. While the enteric panel and bacterial stool culture were negative, the following organism was observed on the modified acid-fast stain (Image 1). This organism measured approximately 9 µm, was variably modified acid-fast, and had a wrinkled-cellophane appearance. The organism was identified as a Cyclospora cayetanensis oocyst. The patient later shared that she had consumed a bagged salad mix that was implicated in the ongoing Cyclospora outbreak.

Image 1. Cyclospora cayetanensis.

Cyclospora cayetanensis

Cyclospora cayetanensis, a coccidian protozoan, is transmitted through ingestion of food or water contaminated with infectious oocysts. While infected humans shed oocysts in their stool, these oocysts are unsporulated and non-infectious at the time of excretion. In order to sporulate and become infectious, these excreted oocysts must incubate in the environment for 7 – 15 days post-excretion. Due to the required incubation post-excretion, direct fecal-oral transmission cannot occur.

Endemic areas include Central and South America, Middle East, South East Asia, and the Indian subcontinent. In non-endemic areas, travelers make up a large proportion of cases. Local outbreaks in non-endemic areas are often due to contaminated food sources. Most commonly the source of these outbreaks arise from consumption of raw fruits and vegetables that are difficult to thoroughly clean. These include leafy green vegetables (salad mixes, lettuce), herbs (basil, cilantro), and raspberries. Moreover, Cyclospora is resistant to many disinfectants used in the food industry. As exposure to this parasite is through contaminated food and water, infected patients are also at risk for other food and waterborne parasites including Cryptosporidium.

Once infectious oocysts are ingested, symptoms are typically observed after a one week incubation. Clinical presentation of Cyclospora infection includes diarrhea, nausea, fatigue, low grade fever, and weight loss. Although Cyclospora causes infections in both immunocompromised and immunocompetent individuals, symptoms may be severe and prolonged in immunocompromised patients, particularly in HIV and AIDS patients. Children and elderly individuals are also at higher risk for severe disease. Trimethoprim-sulfamethoxazole is the standard treatment. If untreated, symptoms can last for 10 – 12 weeks and may exhibit a relapsing pattern.

Stool samples should be submitted to the clinical microbiology laboratory for microscopic and/or molecular studies. To increase recovery of the organism during intermittent or low burden shedding, multiple stool specimens should be submitted over 2 -3 days. When viewed under a UV fluorescent microscope, Cyclospora oocysts autofluoresce and appear blue or green. While safranin-based stains or UV fluorescent microscopic examination can be used, modified acid-fast staining is commonly performed for the microscopic identification of Cyclospora. Cyclospora oocysts are modified acid-fast variable and measure 8 – 10 µm in diameter, unlike Cryptosporidium oocysts which are modified acid-fast positive and measure 4 – 6 µm in diameter. It is important to alert the clinical microbiology lab if suspecting Cyclospora as stains used in routine O&P exam, including trichrome stains, are not effective in highlighting Cyclospora. Although lab developed tests and FDA cleared multiplex gastrointestinal pathogen panels including Cyclospora are available, molecular assays are not yet routinely used for identification of Cyclospora due limited widespread availability.

References

  1. Almeria S, Cinar HN, Dubey JP. Cyclospora cayetanensis and Cyclosporiasis: An Update. Microorganisms. 2019;7(9):317. Published 2019 Sep 4. doi:10.3390/microorganisms7090317
  2. Hadjilouka A, Tsaltas D. Cyclospora Cayetanensis-Major Outbreaks from Ready to Eat Fresh Fruits and Vegetables. Foods. 2020;9(11):1703. Published 2020 Nov 20. doi:10.3390/foods9111703
  3. Ortega YR, Sanchez R. Update on Cyclospora cayetanensis, a food-borne and waterborne parasite. Clin Microbiol Rev. 2010;23(1):218-234. doi:10.1128/CMR.00026-09
  4. Garcia LS. Diagnostic Medical Parasitology. 6th Edition. 2016.
  5. Casillas SM, Bennett C, Straily A. Notes from the Field: Multiple Cyclosporiasis Outbreaks — United States, 2018. MMWR Morb Mortal Wkly Rep 2018;67:1101–1102. DOI: http://dx.doi.org/10.15585/mmwr.mm6739a6

Paige M.K. Larkin, PhD, D(ABMM), M(ASCP)CM is the Director of Molecular Microbiology and Associate Director of Clinical Microbiology at NorthShore University HealthSystem in Evanston, IL. Her interests include mycology, mycobacteriology, point-of-care testing, and molecular diagnostics, especially next generation sequencing.

The Red Queen’s Gambit: Helping the Lab Avoid Burnout

In Lewis Carroll’s book Through the Looking Glass, Alice is being given a tour of Looking-Glass Land by the Red Queen when this happens:

Alice never could quite make out, in thinking it over afterwards, how it was that they began: all she remembers is, that they were running hand in hand, and the Queen went so fast that it was all she could do to keep up with her: and still the Queen kept crying “Faster! Faster!” but Alice felt she could not go faster, though she had not breath left to say so.

However, after running until Alice feels absolutely exhausted she looks around in surprise to find that they are exactly in the same place where they had begun.

Carroll, Lewis (1991) [1871]. “2: The Garden of Live Flowers”. Through the Looking-Glass (The Millennium Fulcrum Edition 1.7 ed.). Project Gutenberg.

“Well, in our country,” said Alice, still panting a little, “you’d generally get to somewhere else—if you ran very fast for a long time, as we’ve been doing.”

“A slow sort of country!” said the Queen. “Now, here, you see, it takes all the running you can do, to keep in the same place. If you want to get somewhere else, you must run at least twice as fast as that!”

Laboratory medicine is one of many areas of healthcare where more is constantly expected to be done with less, where the inhabitants of our looking-glass land have to run as fast as we can just to maintain the status quo. Also like many areas of medicine, our already strained workforce suddenly became victims of an unprecedented global COVID-19 pandemic stressing and stretching our capabilities. The gamble then, is expecting members of our incredible laboratory medicine community to run so fast that they ultimately burn themselves out.

From the December 2020 New York Times article on laboratory workers in the time of COVID-19 titled, “‘Nobody Sees Us’: Testing-Lab Workers Strain Under Demand“:

Morale in the labs has flagged as the country continues to shatter records for caseloads, hospitalizations and deaths. The nation’s testing experts know these statistics better than anyone: They count the numbers themselves, sample by sample. But they are also easy targets of criticism and complaint.

“There is always this undercurrent of, it’s never good enough,” said Dr. Abbott, of Deaconess Hospital in Indiana. “It’s devastating. We’re working as hard as we can.”

In April 2020, just a few weeks after COVID-19 was officially declared a global pandemic, the April issue American Journal of Clinical Pathology opened with two timely editorials, one from Dr. Jeanette Guarner discussing the three emergent coronavirus diseases of the past two decades (SARS, MERS and COVID-19) and the next by Dr. Steven H Kroft titled “Well-Being, Burnout, and the Clinical Laboratory.”

In this issue were three different articles, the results of extensive surveys conducted by the ASCP to determine the job satisfaction, well-being and burnout prevalent among 1) pathologists, 2) pathology residents and fellows, and 3) laboratory professionals. Knowing now what clinical laboratories, leaders and trainees were about to go through thanks to COVID-19, made these publications about the stress and satisfaction felt by those in lab medicine was timely (if not grimly ironic).

What is shown in those excellent publications, and what we can only assume has become more true, is “burnout,” (the “combination of emotional exhaustion, depersonalization, and loss of sense of personal accomplishment”) prevalent in laboratory medicine, with the majority of pathologists, residents and fellows, and professionals reporting having experienced it if not experiencing it as an ongoing problem.

There is no single solution to burnout in the laboratory. As Dr. Kroft outlines in his editorial, these surveys can be seen as initial steps to understanding the problem and plotting potential courses forward (“a roadmap for what workplace landmines to try to avoid.”). But several meaningful pieces of data emerged from these surveys as well: Overwhelmingly, pathologists and lab professionals enjoy their work (91% and 86%) and feel valued by their colleagues (79% and 71%). Also telling is the fact that while well over 90% of laboratory professionals reported “a little bit of stress” to “a lot of stress,” 2/3rds of them reported feeling either “somewhat satisfied” or “very satisfied” with their jobs. Clearly, no one knows the value of laboratory medicine better than those of us doing it. But recognition and support coming from within the laboratory space should be seen as a good first step to acknowledging these contributions.

Recognition is needed from outside lab leadership as well, and especially should be accompanied by both stress-reducing measures (filling labor gaps, adequate compensation and benefits etc.) and opportunities to feel ownership and personal investment in the contributions we make to healthcare. Healthcare leaders, professional organizations, and all of those who were vocal supporters of labs’ contributions during the worst of the pandemic, should continue to advocate on behalf of laboratory staff’s well-being.

Even as vaccines and other mitigation efforts are providing more widespread pandemic relief in the United States, it’s clear that we are now through a COVID-19 looking glass. The lab was already running as fast as it could, but to get us to where we are now, many of us started running twice as fast. Hopefully we will both continue to run and also be supported in that ongoing race to stay where we are.

-Dr. Richard Davis, PhD, D(ABMM), MLS(ASCP)CM is a clinical microbiologist and regional director of microbiology for Providence Health Care in Eastern Washington. A certified medical laboratory scientist, he received his PhD studying the tropical parasite Leishmania. He transitioned back to laboratory medicine (though he still loves parasites!), and completed a clinical microbiology fellowship at the University of Utah/ARUP Laboratories in Utah before accepting his current position. He is a 2020 ASCP 40 Under Forty Honoree.

TRANSforming Healthcare: The Role of The Laboratory

In 2006, an international group of human rights experts assembled in Yogyakarta, Indonesia to address patterns of discrimination and abuse of individuals related to sexual orientation and gender identity. This document, The Yogyakarta Principles: Principles on the application of

international human rights law in relation to sexual orientation and gender identity, has been widely accepted as setting the standards for fundamental human rights for all, with specific attention to sexual orientation and gender identify. It is worth studying, as it articulates rights in many domains of everyday life. Of direct relevance to our Profession are Principle #12, The Right to Work; Principle number #17, The Right to the Highest Attainable Standard of Health; and Principle #18, Protection from Medical Abuses.1  It is the goal to “Adopt the policies, and programmes of education and training, necessary to enable persons working in the healthcare sector to deliver the highest attainable standard of healthcare to all persons, with full respect for each person’s sexual orientation and gender identity.”

Because the medical laboratory provides critical data for patient management, laboratory professionals and pathologists must be able to evaluate laboratory and biopsy results wisely and appropriately.  Yet we often lack fundamental and essential information necessary to support optimal and personalized care for patients on cross-sex hormones.

The number of individuals who self-identify as transgender has risen significantly in the past decade. Transgender people face discrimination, harassment, abuse, and denial of legal rights. They often feel unsafe, and a high proportion face bullying at school or at work. The Centers for Disease Control (CDC) estimates that about 2% of high school students in the U.S. identify as transgender; among them, 35% attempt suicide. Transgender adults are twice as likely of being homeless, four times more likely to live in poverty, four times as likely as being HIV-infected, and twice as likely to be unemployed compared to the general population.2 Individuals without access to appropriate care may purchase hormones from unreliable sources, so that the dose, drug contents, and potential side-effects are poorly controlled or even toxic.

Healthcare systems often fail the transgender community. First, given the high rate of poverty, unemployment, and homelessness, access to basic health services is not available for many individuals. Second, even in those healthcare institutions that serve the uninsured, appropriate services are often lacking, including the absence of knowledgeable providers and the lack of cultural competency in the institution. The few academic hospitals with services and clinics oriented to serving transgender patients struggle to provide optimal care, because there are important gaps in knowledge regarding how best to care for transgender patients. Many health care clinics and professionals lack training in asking all patients “What pronouns do you prefer to use in referring to yourself?” This is a straightforward way to acknowledge gender diversity and sets the first stage of a potentially trusting relationship.


Examples abound regarding information gaps in managing patients on cross-sex hormones. For instance, there are only a handful of papers in the literature addressing care of elderly patients, and little is known about the risks or health benefits of long-term cross-sex hormone use. For children who elect to start puberty blockers so that their development in adolescence is more appropriate to their self-identified gender, long-term effects on bone health are poorly understood. A number of laboratory tests have different reference ranges for “men” and “women,” such as n-telopeptide as a marker of bone turnover. Most labs have not established appropriate reference ranges for patients on cross-sex hormones, nor are there good long-term studies to help guide management of bone health in this setting. And there may be times when the managing health care professionals do not realize that a patient is taking cross-sex hormones.

Patient identifiers are often incomplete. Many patients on cross-sex hormones have not had surgery to remove their gonads. Therefore, a trans-man can present to the Emergency Room with severe abdominal pain, but those managing his care may not suspect ovarian torsion, ectopic pregnancy, or other conditions of the fallopian tubes, ovaries, uterus, and cervix. Similarly, trans-women may have testes and prostates. Most patient registration systems lack the ability to record sex chromosomes and gender identity separately. Also, many individuals identify as non-binary; some are not taking cross-sex hormones at all. These factors affecting presentation are currently captured poorly. If at all, in the medical record but may have profound implications for care. Otherwise, implicit biases can adversely affect patient care.

Finally, we all have work to do to ensure that our patients and colleagues feel welcomed and respected in our labs, training programs, and hospitals. One important step is for each of us to gain self-awareness of our attitudes and biases, and to educate ourselves. A good starting place is Gupta’s article in Lab Medicine;3 another is the book Trans Bodies, Trans Selves by psychologist Laura Erickson-Schroth.4 Second, we must continue to foster inclusive workplaces, to stand up when we witness abuses or so-called “microagressions.” Third, we must work directly with patients to hear their concerns, and to provide the information needed regarding our lab results and pathology reports. We must respond to the gaps identified by our patients, do the research necessary to get better answers, and partner with other health care professionals to address the needs of our patients.

References

  1. The Yogyakarta Principles. 2017. https://yogyakartaprinciples.org/
  2. Meerwijk EL, Sevelius J. Transgender population size in the United States- a Meta-Regression of Population-Based Probability Samples. Am J Public Health 2017; 107(2):e1-e8. PMID 28075632
  3. Gupta S, Imborek KL, Kraswoski MD. Challenges in transgender healthcare: the pathology perspective. Lab Medicine 2016;47:3;180–188.
  4. Erickson-Schroth L. Trans Bodies, Trans Selves: A Resource for the Transgender Community. 2014, Oxford University Press.

-Dr. Upton is board certified in Anatomic Pathology and Cytology and directed an autopsy service and forensic pathology fellowship program at Beth Israel Deaconess Medical Center in Boston, Massachusetts. She has also practiced cytopathology and general surgical pathology, and has focused on genitourinary pathology, head and neck pathology, and gastroenterology (GI) and liver pathology. From 1982-85 and 1987-2002, Dr. Upton lived in Boston and taught at Tufts, Boston, and Harvard Universities. Since 2002, she has been at the University of Washington in Seattle, where she formerly directed the GI and Hepatic Pathology Service the Pathology Residency Program and the UW GI and Hepatic Pathology Fellowship. Currently Emeritus Professor of Pathology, she continues to practice Surgical Pathology, Autopsy Pathology, and Cytopathology, and she is one of the specialists at UW in the areas of GI, liver, and pancreatic pathology.

Hematology Case Study: Unusual Lymphocytes Seen in an Apparently Healthy Young Adult

A healthy 30 year old woman visited her primary care physician concerned about a rash with questionable infection on her hands. The physician prescribed an antibiotic for infection and ordered a CBC. From the results below, it can be seen that the patient had a pancytopenia and a relative lymphocytosis.

Table 1. CBC results.
Table 2. Automated differential results

A manual differential was performed on CellaVision and the presence of large, clefted lymphocytes with immature features was noted. A request for pathology review was sent to the pathologist. The pathologist’s review stated “ Atypical lymphocytosis, specimen to be submitted for flow cytometry. Report to follow. Occasional atypical lymphocytes with immature features also noted. Lymphocyte population is predominantly mature”

The peripheral blood sample was sent out for immunophenotyping by flow cytometry and FISH studies. Flow cytology reported “precursor B-cell population expressing CD19, CD10, HLA-DR, and CD34 is identified. Percent of abnormal cells, 30%. These findings are consistent with precursor B-lymphoblastic leukemia.” While we tend to associate a leukemia diagnosis with a high white blood cell count, and the presence of blasts, this patient was unusual in that she did not have a high WBC or blasts seen on the peripheral smear. Pancytopenia in ALL has been noted in literature. A study of new onset pancytopenia in adults showed that the majority of cases were acute myeloid leukemia, but ALL and other lymphomas also caused pancytopenia3. Another study noted that “pancytopenia followed by a period of spontaneous recovery may precede the diagnosis of acute lymphoblastic leukemia.”1 While the pathologist did not identify blasts on this differential, and cells were predominately mature, WBC was very low, and our analyzer did flag “?blasts/abnormal lymphs” and reflexed the manual differential.

Image 1. Clefted lymphocytes seen on peripheral smear.
Image 2. Clefted lymphocytes on CellaVision.
Table 3. FISH report.

Leukemia is a broad term that includes a number of different chronic and acute diagnoses. Chronic and acute forms are further broken down into myeloid and lymphoid and then into subtypes. The French-American-British (FAB) classification of acute leukemias was devised in the 1970’s and 1980’s and was based on cytochemical staining and morphology of cells. These tests were performed manually and relied on what the cells look like under the microscope. The series of stains were used to differentiate myeloblasts from lymphoblasts. I’m old enough that I remember learning about these stains when they were being developed and thinking how amazing they were!

We’ve come a long way since the early 1980’s! Although the FAB diagnostic criteria are not entirely forgotten, the World Health Association (WHO) classification, first published in 2001, has largely replaced the FAB classification. The newest guidelines for Acute Lymphoblastic Leukemias (ALL) were published by WHO in 2016. These new guidelines supplement morphology and cytochemical staining with newer testing which can now identify and distinguish B cell and T cell ALL. In making a diagnosis, peripheral blood and/or bone marrow aspirate samples are subject to flow cytometry immunophenotyping and chromosome testing such as cytogenics or fluorescence in situ hybridization(FISH). Molecular tests can also be done to look for specific gene changes in the leukemia cells. The WHO classification has become preferred because these new tests can give more information that is important for treatment. Prognosis for ALL depends on patient age, WBC counts at diagnosis and these specific test results which tell us which subtype of ALL is present. The presence and identification of chromosomal alterations is important for diagnosis and therapy decisions. Identifying chromosomal alterations can also lead to better risk classification which is significant because of the knowledge that, while rearrangements tend to have poorer outcomes, some rearrangements actually offer a better prognosis. With the future era of individualized, targeted therapy for leukemia, combining conventional cytogenics with molecular and FISH methods will greatly enhance the accuracy of information and provide patients with more specific and customized treatment options.

While ALL is the most common childhood leukemia, it is not as commonly seen in adults. B cell ALL is more common than T cell ALL in all ages, and accounts for about 90% of ALL cases in children and about 75% of ALL cases in adults. Cure rates in children exceed 90% but in adults varies with age and depending on chromosomal alterations. Most B cell ALL subtypes with chromosome translocations tend to have a poorer outcome than those without translocations. As well, younger adults, <50 years old, have better prognosis than older adults.

This patient did not have a BCR/ABL rearrangement or MLL gene locus 11q23 translocation, which both carry poorer prognoses, but she also did not have a translocation between chromosome 12 and 21 or more than 50 chromosomes, both of which offer more favorable prognoses. This young woman therefore would be in an average risk category and appears to have been diagnosed very early in the course of her disease. We have not seen any further workup, as the patient is being treated at another facility. We wish her well in her leukemia treatments.

References

  1. Hasle H, Heim S, Schroeder H, et al. Transient pancytopenia preceding acute lymphoblastic leukemia (pre-ALL). Leukemia. 1995 Apr;9(4):605-608.
  2. Iacobucci I, Mullighan CG. Genetic Basis of Acute Lymphoblastic Leukemia. J Clin Oncol. 2017 Mar 20;35(9):975-983. doi: 10.1200/JCO.2016.70.7836. Epub 2017 Feb 13. PMID: 28297628; PMCID: PMC5455679
  3. Bone Marrow evaluation in new onset pancytopenia. Human Pathology. Vol 44, Issue 6. June 2013
  4. Hematology: Basic Principles and Practice, 7th Edition. Ronald Hoffman, Edward J. Benz, et al. 2018 Elsevier
Socha-small

-Becky Socha, MS, MLS(ASCP)CMBBCM 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 40 years and has taught as an adjunct faculty member at Merrimack College, UMass Lowell and Stevenson University for over 20 years.  She has worked in all areas of the clinical laboratory, but has a special interest in Hematology and Blood Banking. She currently works at Mercy Medical Center in Baltimore, Md. When she’s not busy being a mad scientist, she can be found outside riding her bicycle.

AIDS/HIV, the LGBTQ Community, and PRIDE Month: A Reflection

This reflection is dedicated with gratitude to the many LGBTQ activists who courageously engaged with politicians, scientists, and health leaders to advance the care of patients worldwide.

Forty years ago this month, near the end of my second year in Pathology Residency, Morbidity and Mortality Weekly Report reported a small case series in its June 5, 1981 issue describing Pneumocystis pneumonia in 5 homosexual men. Soon there were additional reports of gay men affected by P. carinii (now renamed P. jiroveci) pneumonia, Kaposi sarcoma, and other unusual opportunistic infections. These riveting descriptions signaled a new disease entity, soon known as Acquired Immunodeficiency Syndrome (AIDS). Initially some labeled AIDS “the gay disease” or “the gay cancer,” and the fear and stigma associated with AIDS led to discrimination, including evictions from housing, threats of evictions of clinics that served AIDS patients, and fear among some people of even casual contact with people affected by the disease.

At that time, I was training in a tight-knit cohort of residents who studied and socialized together. In those days we performed autopsies in street clothes, with only plastic aprons and gloves as “protective gear”- no masks, no face shields or goggles, no scrub suits. Within a few months of the MMR report, after AIDS fatalities in our training hospital, many of us went to the Autopsy room to observe the unusual findings at our gross organ review rounds, which were same-day examinations of fresh tissue. The next year, in the summer of 1982, I was married in a small ceremony that included only family and a few of my parents’ closest friends. Several years later two men who attended my wedding died of AIDS, and two of my fellow residents, and their partners, also died of AIDS.

By December, 1982, AIDS had been reported in a baby who had received multiple blood transfusions, and in January, 1983, AIDS was documented in women who had been sexual partners of men with AIDS and in people injecting drugs. These reports dispelled the idea that AIDS was unique to the gay community and suggested that the disease was likely due to an infectious agent that could be transmitted through blood, blood products, and sexual contact. Then in my Fellowship, still performing many autopsies, I was amazed at the dramatic change in protocols that appeared nearly overnight, as we were now required to use personal protective equipment for any work involving blood and fresh tissues. We gowned, double-gloved, wore masks and face shields, scrubs, and shoe covers when performing autopsies; and we were trained more diligently in managing needles and scalpel blades, as well as safety in procedures.

Pathologists and laboratory professionals soon learned to identify opportunistic infections that previously had been extremely rare outside the setting of severe immunosuppression. Multiple concurrent opportunistic infections were so common that it became second nature to scan any microscopic tissue section for cytomegalovirus, toxoplasmosis, fungal infection, atypical Mycobacteria, Kaposi sarcoma, and other findings. I learned from firsthand experience that there may not always be a single unifying diagnosis, in the sense that an immunocompromised patient may suffer with multiple infectious agents. By 1987, as a young attending pathologist on weekend call, I had to learn to perform by hand special rapid Gomori methenamine silver stains on any cases that required them. (As case numbers increased, the service began to employ histotechnologists to cover the weekends.)

Discovery of the causative infectious agent, Human Immunodeficiency Virus (HIV), by groups led by Montagnier (1983) and by Gallo (1984), was a critical step for the development of an accurate serologic test (1985) to detect pre-symptomatic disease. Publication of the retroviral sequence later facilitated the development of treatments, such as AZT, which was approved in 1987, and later to Highly Active Antiretroviral Therapy (HAART) in 1997. The development of effective antiretroviral therapies along with accurate and sensitive laboratory tests for HIV offered the opportunity to test and treat asymptomatic people before they developed severe immunosuppression and opportunistic infections.  

This abbreviated summary greatly understates the devastating toll that the pandemic has wreaked and continues to wreak. Millions of young and middle-aged people across the globe, of all nationalities, in all communities, have died. Many children were orphaned. Those of my generation continue to mourn the losses of the people we loved and wonder in grief at the creativity and potential contributions also lost to our society and culture.

And, sadly, HIV rages on. Intravenous drug users and men who have sex with men continue to face discrimination and abuse in many countries. Access to preventive therapy and lifesaving (but not yet curative) antiretroviral treatment is still denied or unavailable to many patients. Efforts to develop an effective vaccine have been unsuccessful to date. Work to address the global nature of this pandemic have required international cooperation and coordinated efforts, that continue to this day. The current extensive global health activities of ASCP stem greatly from the Society’s early invitation to set up HIV testing for the PEPFAR (President’s Emergency Plan for AIDS Relief) effort, which has also led to engagement in laboratory quality improvement efforts and workforce training worldwide. Finally, as we honor our LGBTQ colleagues, patients, and family members during PRIDE month, it is important to acknowledge that members of LGBTQ Community have been at the forefront of health care advocacy since the HIV pandemic first emerged. The tremendous progress in treatment, testing, and global strategies are results of their continuing energy, initially in the U.S. and now around the world to help other communities. We are all indebted to HIV/AIDS activists, such as the Gay Men’s Health Crisis and ACT UP, who have engaged politically, staged public awareness-building efforts, and challenged political and health care leaders and research scientists to address the emergency posed by the infection. Their efforts led to greatly accelerated treatment trials and effective treatments, and they have fought to have drug costs lowered to increase access. They can take great PRIDE in their lasting contributions to help patients everywhere.

-Dr. Upton is board certified in Anatomic Pathology and Cytology and directed an autopsy service and forensic pathology fellowship program at Beth Israel Deaconess Medical Center in Boston, Massachusetts. She has also practiced cytopathology and general surgical pathology, and has focused on genitourinary pathology, head and neck pathology, and gastroenterology (GI) and liver pathology. From 1982-85 and 1987-2002, Dr. Upton lived in Boston and taught at Tufts, Boston, and Harvard Universities. Since 2002, she has been at the University of Washington in Seattle, where she formerly directed the GI and Hepatic Pathology Service the Pathology Residency Program and the UW GI and Hepatic Pathology Fellowship. Currently Emeritus Professor of Pathology, she continues to practice Surgical Pathology, Autopsy Pathology, and Cytopathology, and she is one of the specialists at UW in the areas of GI, liver, and pancreatic pathology.

The Great Mimicker

I’ve witnessed that radiologists are often hesitant to perform a core biopsy on a spleen due to its vascularity, so when I attend spleen FNAs, I rarely push. Even when the oncology team requests both a core biopsy and FNA for a hematology workup, I will acquire as many passes as possible from an FNA to work up cytomorphology and flow cytometry before risking a core-induced hemorrhagic complication. When I was called to attend an ultrasound-guided spleen biopsy, I went in knowing two things: the patient has both splenic and brain lesions, and I was going to make the most of what I was given. When I arrived in ultrasound, the radiologist informed me that the patient had polycythemia vera (PV), which would explain the splenomegaly, but not the brain lesions. The patient, a 65 year old male, received the diagnosis in 2009 and was managed with phlebotomies for six years until a rising platelet and white blood cell count required an intervention of hydroxyurea. Within 18 months, the patient developed a PE and dizziness and began therapeutic anticoagulation. At the same time, the patient’s “metastatic lesions” were identified on imaging. The first state of business is finding out if his PV had progressed into myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). There was something… off… about this case though. It didn’t feel like a heme case (not that I prefer non-heme cases… well, okay, I’m a cytotech, so I kind of do). The brain lesions concerned me, and I didn’t know what to infer.

Let’s progress to the FNA. Here are the air-dried, Diff-Quik smears that changed everything.

Images 1-2: Splenic mass, fine needle asperation, DQ-stained smears.

What non-heme surprise is THIS?! Are these histiocytes? There’s no way, those nucleoli are aggressive! Look at the chromocenters! The variation in nuclear size! What epithelial beauty is this? Is it epithelial?! Is that a fibrovascular core? It can’t be sarcomatoid, could it? Twenty inner monologue questions later, “okay, it’s adequate,” I said to the radiologist. But wait… should I do it? Should I press for a core biopsy? The radiologist asked me if I needed anything else for the diagnosis. Perhaps she saw my puzzled expression, compelling her to tell me that she felt the imaging looked weird – she thought it wasn’t a heme case either. At least I’m not alone here. I took a deep breath, expecting the worst and hoping for the best, and I asked the radiologist to collect a core biopsy. She checked the ultrasound Doppler for excessive vascularity, and much to my surprise, she agreed to perform the core. After collecting more FNAs for my cell block and dropping the core biopsies off in surgical pathology, I showed the case to my attending pathologist. He also agreed that we don’t need to triage it for heme. He asked if the patient had any significant history other than PV, splenic lesions, and brain mets, and I told him nothing was reported in his chart. I checked the chart again for good measure while he was running through his differential diagnoses of lung, GI, prostate, etc., and saw the patient was scheduled to see dermatology later that week. I mentioned to that to my attending, and he suggested it could be a melanoma.

The following morning, I examined the pap-stained slide and began to second guess myself. Was I wrong? Could it be a heme case? Hodgkin’s wasn’t in the differential, and these cells look so much more aggressive than Reed-Sternberg cells. At least we have a core biopsy either way. We could run immunos on the cell block and save the cores for molecular. I screened the pap-stained slides a little longer, focusing on the macronucleoli, the owl-eye and eccentric nuclei, the poorly-differentiated nature of this… MELANOMA. YES! So, the cells might not contain any melanin pigment, but my attending’s inkling was exactly right. Waiting for my cell block to arrive, I listed melanoma as my primary diagnosis with a differential of lung or prostate cancer.

Images 3-4: Splenic mass, fine needle aspiration, Pap-stained smear.

The cell block confirmed my non-heme diagnosis and kept my differentials at bay. The attending pathologist ordered an immunohistochemistry profile of S100, HMB-45, and Melan A, as well as AE1/AE3. The first three immunostains (prior to our adoption of SOX-10) confirmed a diagnosis of metastatic malignant melanoma. Soon thereafter, the patient’s primary lesion was identified on his back, and he was treated with radiation and immunotherapy. Unfortunately, the metastases were not responding to the immunotherapy, and a few days after a clinical trial was offered, the patient passed away.

Images 5-8: Splenic mass, fine needle aspiration. 5 and 6, cell block, H&E; 7 and 8, Melan A+.

Melanoma is known as the great mimicker, especially in amelanotic form, and it should always be in the back of your mind as a differential diagnosis. Lack of melanin pigment and a large cherry red macronucleoli leads us to favor lung, prostate, or serous adenocarcinoma), renal cell carcinoma, hepatocellular carcinoma, Hodgkin’s lymphoma, or even an epithelioid sarcoma. This case highlights the need to remember that metastatic melanoma is always a possibility, even when you do not have a primary site or previous clinical history of the disease.

-Taryn Waraksa, MS, SCT(ASCP)CM, CT(IAC), has worked as a cytotechnologist at Fox Chase Cancer Center, in Philadelphia, Pennsylvania, since earning her master’s degree from Thomas Jefferson University in 2014. She is an ASCP board-certified Specialist in Cytotechnology with an additional certification by the International Academy of Cytology (IAC). She is also a 2020 ASCP 40 Under Forty Honoree.

The ABCs For Designing Sustainable Public Health Initiatives: A Simple Framework For Program Planners

If there is anything the COVID-19 pandemic has taught us, it is the fact that the world is a global village with no country being completely immune from the effects of disease and pathogens. With migration across borders along with its attendant effects of disease dissemination, public health initiatives aimed at improving the health outcomes of populations must be designed with the target population in mind and long-term sustainability prioritized. The health of a community is dependent on the overall health of its people. Public health initiatives are often designed to modify health and disease patterns within groups of people. A key measure of success of any health initiative is its long-term sustainability. Therefore, a framework to guide program planners at the design stage of any public health program is critical to success. This framework can be summed up as the ABCs for designing sustainable public health initiatives.

Appraisal: Appraisal is defined as an act of assessing something or someone. It is an evaluation of a process, system, or population. An appraisal of any given situation or entity is carried out to give the full picture, without redundancy or superfluity. When a thorough appraisal is carried out, it elaborates the situation on the ground, and the best approaches to tackle any challenges. For an appraisal of a public health problem, the following key activities should be included in the program design.

  1. Root Cause Analysis: A Root Cause Analysis (RCA) is a term that describes techniques and tools used to uncover the causes of a problem or failure.1 A RCA is often carried out to get to the bottom of a problem, and not to only focus on the offshoot of the problem-the observable symptom. A thorough RCA defines the problem, answers all the ‘why’ questions, and proffers solutions that lend themselves to evaluations which address the problems.
  2. Social Determinants of health: What makes one community healthy, and the other unhealthy? What factors contribute to the well-being of communities? The social determinants of health are a consortium of factors apart from medical care that can be influenced by social policies and shape health in powerful ways.2 It is important to note that what may positively impact the health of one community, may negatively impact the health of another. Public health practitioners must be able to determine the most important influencers to health and diseases in any community, to potentiate the cost-effectiveness of any intervention. The social determinants of health can be summed up as the 3 G’s:
  3. Geography-The physical environment and all the elements of nature. These include access to clean drinking water, healthy food portions, climate change, global warming, etc.
  4. Goods-These includes the social and economic environment. People’s relationships, income levels, social status, education levels, etc.
  5. Genes-These includes a person’s genetic make-up, which has been shown to have a great impact on health and certain diseases.

Therefore, a thorough analysis and understanding by public health practitioners on the most important contributor to health, and targeting resources to such areas, will increase the likelihood of success of any health intervention or campaign.

  • Influence of Community Stakeholders: A stakeholder’s analysis is a process of systematically gathering and analyzing qualitative information to determine whose interests should be taken into account when developing and/or implementing a policy or program.3 The stakeholders in a process are actors (persons or organizations) with a vested interest in the policy or program being implemented.3 After conducting a stakeholder analysis of the key interest groups, it is imperative to determine the influence of community stakeholders on the proposed public health initiative. Community leaders have a great influence on their constituents. Therefore, the success or ultimate failure of a project depends in part on the role of these key community actors. Vital questions must be asked and answered including but not limited to: what is their interest in the project? What is their knowledge of the project? Do they have an adequate understanding of the major root causes of the problem? Do they proffer alternate ways to address the problem? What is their voting power in the decision-making process? These are some of the key factors that may be considered when trying to determine the influence of community stakeholders on the proposed health intervention.
  • The Role of health models on disease causation, interpretation, and outcomes: The role of the models of health on disease incidence and survival cannot be overlooked. At the crux of any public health problem is the answer to some ‘why’ questions. It is a well-known fact that models of health including the religious, biomedical, psychosomatic, humanistic, existential and transpersonal all have a role to play in disease incidence and survival to varying degrees.4 While one model may play a more significant role in one community, the same may not be the case in another community. For example, while infections and communicable diseases are still a huge burden in many developing countries5 due to environmental and biophysical concerns including limited access to immunizations, the same is not the case in developed countries. Developed countries tend to grapple more with chronic diseases6 such as obesity, diabetes, hypertension, cancers. It is therefore the responsibility of program planners to determine during the design stages of projects, the models with greater impacts on disease causation and outcome. This approach may increase the likelihood of success than the failure of the intervention.

Budget: A budget is a financial statement detailing the income and expenditure of an entity over a given period. Proper budgeting encompasses adequate planning, both for foreseeable and unforeseeable expenditures. A budget should also include the fixed assets and in-kind or monetary contributions of the program to the execution of any public health initiative. A comprehensive budget should take into account direct and indirect costs including but not limited to personnel costs, travel costs, equipment/supplies, consultants, printing/duplication costs, postage, staff training, rent, telephone expenses, heavy machinery, etc. A project with an insufficient budget would be more likely to encounter challenges that may pose as threats to its sustainability, than one which is adequately funded. Therefore, program planners must ensure that their budgets are sufficient enough to run through the entire lifecycle of the projects.

Community buy-in: It would be an effort in futility if after going through the planning and design phases of a project, you discover that a community is not interested in that line of intervention. This would amount to a humungous waste of time and valuable resources. Therefore, program planners must ensure during the design phase of any project, to get the community’s perspective on that particular line of program approach. This is imperative because apart from getting the community’s perspective on a particular proposal, they may also be able to provide valuable pieces of information that may enhance the sustainability of any project. Community buy-in works in tandem with the role of the community’s stakeholders. Successful programs are designed for the people and with the people. In summary, at the crux of any planned public health intervention is the issue of long-term sustainability. Program planners should become familiar with addressing fundamental elements of successful program interventions. A good place to start is ensuring

References

  1. https://www.tableau.com/learn/articles/root-cause-analysis
  2. Braveman P, Gottlieb L. The social determinants of health: it’s time to consider the causes of the causes. Public Health Rep. 2014;129 Suppl 2(Suppl 2):19-31. doi:10.1177/00333549141291S206
  3. https://www.who.int/workforcealliance/knowledge/toolkit/33.pdf
  4. Tamm ME. Models of health and disease. Br J Med Psychol. 1993;66 ( Pt 3):213-228. doi:10.1111/j.2044-8341.1993.tb01745.x
  5. Tadesse GA, Javed H, Thanh NLN, et al. Multi-Modal Diagnosis of Infectious Diseases in the Developing World. IEEE J Biomed Health Inform. 2020;24(7):2131-2141. doi:10.1109/JBHI.2019.2959839
  6. Silvaggi F, Eigenmann M, Scaratti C, et al. Employment and Chronic Diseases: Suggested Actions for The Implementation of Inclusive Policies for The Participation of People with Chronic Diseases in the Labour Market. Int J Environ Res Public Health. 2020;17(3):820. Published 2020 Jan 28. doi:10.3390/ijerph17030820

-Evi Abada, MD, MS is a Resident Physician in anatomic and clinical pathology at the Wayne State University School of Medicine/Detroit Medical Center in Michigan. She earned her Masters of Science in International Health Policy and Management from Brandeis University in Massachusetts, and is a global health advocate. Dr. Abada has been appointed to serve on the ASCP’s Resident’s Council and was named one of ASCP’S 40 under Forty honorees for the year 2020. You can follow her on twitter @EviAbadaMD.