Characterizing the role of informal payments in the delivery of pathology and clinical laboratory services.

OBJECTIVES: Informal payments (IPs) are unofficial cash or in-kind payments for goods or services that should be covered by the health care system. They are a common but regressive method of financing health care in low- and lower-middle-income countries (LMICs). This study aims to characterize the prevalence and impact of IPs on pathology and laboratory medicine (PALM) services. METHODS: From September 2021 to September 2022, PALM staff were surveyed about the frequency, determinants, and impacts of IPs in their respective workplaces. RESULTS: In total, 268 responses were received, and 46.6% (125/268) reported experience with IPs. These 125 participants were more likely to work in the public sector and in LMICs. Approximately 65% reported accepting IPs to perform tests or release results. Obtaining faster results was the most commonly perceived reason for patients offering IPs. Overall, participants reported that IPs had more negative than positive impacts on their workplace. CONCLUSIONS: This represents a first step in characterizing IPs within PALM and how this practice may affect access to these services in LMICs. Specifically, the fact that faster turnaround time was the most frequently perceived reason for offering IPs uncovers a potential barrier to improving PALM capacity in these regions.

Corruption in the health sector: A problem in need of a systems-thinking approach.

Health systems are comprised of complex interactions between multiple different actors with differential knowledge and understanding of the subject and system. It is exactly this complexity that makes it particularly vulnerable to corruption, which has a deleterious impact on the functioning of health systems and the health of populations. Consequently, reducing corruption in the health sector is imperative to strengthening health systems and advancing health equity, particularly in low- and middle-income countries (LMICs). Although health sector corruption is a global problem, there are key differences in the forms of and motivations underlying corruption in health systems in LMICs and high-income countries (HICs). Recognizing these differences and understanding the underlying system structures that enable corruption are essential to developing anti-corruption interventions. Consequently, health sector corruption is a problem in need of a systems-thinking approach. Anti-corruption strategies that are devised without this understanding of the system may have unintended consequences that waste limited resources, exacerbate corruption, and/or further weaken health systems. A systems-thinking approach is important to developing and successfully implementing corruption mitigation strategies that result in sustainable improvements in health systems and consequently, the health of populations.

Pathologists Overseas: A volunteer-based model for building sustainable, high-quality pathology and laboratory medicine services in low- and middle-income countries.

For thirty years Pathologists Overseas (PO) has worked in low- and middle-income countries (LMICs) to provide affordable, sustainable, and high-quality pathology and laboratory medicine (PALM) services through strategic partnerships and the efforts of our large volunteer network. We address low quality diagnostic services by targeting the 3 pillars of PALM quality: human resources, systems, and quality and accreditation. To improve human resource capacity, PO and our partnering organizations provide virtual continuing education to pathologists and laboratory professionals in these countries. To improve systems, we provide laboratory information system installation and implementation support. Lastly, to improve quality and help laboratories progress toward accreditation, we support an external quality assurance program for laboratories in LMICs. As a relatively small organization, PO demonstrates that a network of dedicated volunteers, in partnership with corporations and professional organizations, can initiate sustainable change in the quality of PALM services in LMICs by focusing efforts on the core components of laboratory quality.

Corruption: An Impediment to Delivering Pathology and Laboratory Services in Resource-Limited Settings.

OBJECTIVES: Corruption is a widely acknowledged problem in the health sector of low- and middle-income countries (LMICs). Yet, little is known about the types of corruption that affect the delivery of pathology and laboratory medicine (PALM) services. This review is a first step at examining corruption risks in PALM. METHODS: We performed a critical review of medical literature focused on health sector corruption in LMICs. To provide context, we categorized cases of laboratory-related fraud and abuse in the United States. RESULTS: Forms of corruption in LMICs that may affect the provision of PALM services include informal payments, absenteeism, theft and diversion, kickbacks, self-referral, and fraudulent billing. CONCLUSIONS: Corruption represents a functional reality in many LMICs and hinders the delivery of services and distribution of resources to which individuals and entities are legally entitled. Further study is needed to estimate the extent of corruption in PALM and develop appropriate anticorruption strategies.

Immunophenotypic Characterization and Purification of Neoplastic Cells from Lymph Nodes Involved by T-Cell/Histiocyte-rich Large B-cell Lymphoma by Flow Cytometry and Flow Cytometric Cell Sorting.

BACKGROUND: T-cell/histiocyte rich large B-cell lymphoma (THRLBCL) is B-cell lymphoma in which rare neoplastic cells are embedded in a reactive infiltrate. We describe the first characterization of the neoplastic cells by flow cytometry (FC). METHODS: Using FC, we immunophenotyped the neoplastic cells of 11 cases of THRLBCL and 11 cases of DLBCL, NOS (controls). Neoplastic THRLBCL cells were also purified by flow cytometric cell sorting (FCCS). RESULTS: A neoplastic THRLBCL population was detected by FC in 9 of 11 cases (82%). Neoplastic THRLBCL cells demonstrated an aberrant germinal center B-cell immunophenotype (bright CD20, bright CD40; positive for Bcl-6 and CD75; weakly positive for CD32; negative for IgH). With regard to adhesion molecules, CD54 was overexpressed, CD58 expression varied between cases, and CD50 expression was intermediate. Evaluation of immunomodulatory receptors demonstrated that PD-L2 was weakly expressed and PD-L1 was variably expressed. Finally, FCCS of two cases showed large multi-lobated cells with morphology consistent with neoplastic cells of THRLBCL. CONCLUSIONS: The immunophenotype identified and the morphology of the FCCS purified cells confirms the FC defined populations are neoplastic cells from THRLBCL. While the cohort is small, neoplastic THRLBCL cells lack surface immunoglobulins. CD40, CD50, and CD54 were overexpressed in THRLBCL relative to DLBCL, NOS, perhaps contributing to the predominance of T cells in THRLBCL. Expression of CD32, PD-L1, and PD-L2 may be useful in distinguishing THRLBCL and NLPHL. Finally, the FC assays will be useful for purifying neoplastic cells of THRLBCL and for diagnostic immunophenotyping of THRLBCL. © 2019 International Clinical Cytometry Society.

Survey of Global Health Education and Training in Pathology Residency Programs in the United States.

OBJECTIVES: This study assessed the prevalence, general interest, and barriers to implementing global health curricula in pathology residency programs. METHODS: We conducted a survey of 166 US pathology residency programs. RESULTS: Thirty-two (195) of 166 programs responded. Of these, 13% have a formalized global health program (n = 4), and the majority indicated at least some general interest in global health among trainees (88%, n = 28) and faculty (94%, n = 30), albeit at a low to moderate level. Funding limitations, regulatory constraints, and insufficient knowledge of global health were frequently cited barriers to developing a global health program. CONCLUSIONS: Few US pathology departments incorporate global health education into postgraduate training. The importance of pathology in global health has been underappreciated, despite its critical role in the delivery of health care in resource-limited settings. One solution is for pathology departments to expand global health educational opportunities for trainees.

Flow Cytometry for Non-Hodgkin and Hodgkin Lymphomas.

Multiparametric flow cytometry is a powerful diagnostic tool that permits rapid assessment of cellular antigen expression to quickly provide immunophenotypic information suitable for disease classification. This chapter describes a general approach for the identification of abnormal lymphoid populations by flow cytometry, including B, T, NK, and Hodgkin lymphoma cells suitable for the clinical and research environment. Knowledge of the common patterns of antigen expression of normal lymphoid cells is critical to permit identification of abnormal populations at disease presentation and for minimal residual disease assessment. We highlight an overview of procedures for processing and immunophenotyping non-Hodgkin B- and T-cell lymphomas and also describe our strategy for the sensitive and specific diagnosis of classical Hodgkin lymphoma and nodular lymphocyte predominant Hodgkin lymphoma.

Role of p16 testing in cervical cancer screening among HIV-infected women.

BACKGROUND: p16 immunohistochemistry is used to evaluate for HPV-associated cervical intraepithelial neoplasia. The diagnostic performance of p16 in HIV infection is unclear. METHODS: Between June-December 2009, HIV-infected women underwent Papanicolaou (Pap) smear, human papillomavirus (HPV) testing, visual inspection with acetic acid (VIA), and colposcopy-directed biopsy as the disease gold standard at a HIV clinic in Kenya. Pap smears were evaluated for p16 expression. Sensitivity, specificity, positive predictive value (PPV), and area under the receiver operating characteristic curve (AUC) of p16 to detect CIN2/3 on histology and the impact of immunosuppression and ART was assessed. RESULTS: Of 331 cervical samples with p16 expression, p16 sensitivity and specificity to detect CIN2/3 was 54.1% and 72.4% respectively, which was lower than Pap and HPV in sensitivity, but higher in specificity than Pap, HPV, and VIA. Combining tests and p16 reduced sensitivity and increased specificity of Pap from 90.5% to 48.7% and 51.4% to 81.7%; of VIA from 59.5% to 37.8% and 67.6% to 89.9%; and of HPV from 82.4% to 50.0% and 55.3% to 84.8%. Combination p16 increased the PPV of Pap from 34.9% to 43.4%; of HPV from 34.7% to 48.7%; and VIA from 34.9% to 51.9%. Adjunctive p16 did not change AUC (P>0.05). P16 performance was not altered by immunosuppression or ART use. Combining p16 with HPV and VIA reduced the variation in HPV and VIA performance associated with CD4 and ART. CONCLUSION: As an adjunctive test in HIV-infected women, p16 immunohistochemistry increased specificity and PPV of HPV and VIA for CIN2/3, and was not altered in performance by immunosuppression, ART, or age.

Use of a computer-based provider order entry (CPOE) intervention to optimize laboratory testing in patients with suspected heparin-induced thrombocytopenia.

INTRODUCTION: Heparin-induced thrombocytopenia (HIT) is a rare but frequently considered diagnosis in hospitalized patients. Despite the availability of clinical prediction tools, HIT is often over-diagnosed and patients can be subjected to unnecessary and expensive testing. METHODS: A decision-support tool requiring providers to calculate the 4Ts (HIT risk) score prior to ordering laboratory-based tests for anti-PF4/heparin antibody enzyme-linked immunosorbent assay (ELISA) testing was implemented at our institution in January 2014. Charts of adult patients who underwent ELISA or serotonin release assay (SRA) testing during the 8-month time periods prior to and following this intervention were reviewed and 4Ts scores at the time of ELISA or SRA testing were calculated. RESULTS: A total of 443 ELISA and SRA tests were sent for 411 patients during the time periods studied. We observed a significant decrease from 43 tests/month before to 22 tests/month (p < 0.001) after the intervention. A total of 337 charts were reviewed. We observed a trend toward decrease in the proportion of tested patients with low 4Ts scores (66% vs 56%, p = 0.069), as well as an increase in the average 4Ts score of tested patients (3.0 vs 3.4, p = 0.010) following our intervention. DISCUSSION: Over-testing and treatment for HIT are frequent and potentially harmful occurrences in hospitalized patients. Our study demonstrates that a clinical decision support tool embedded within the electronic ordering process can decrease unnecessary testing for HIT.

Mosaicism of podocyte involvement is related to podocyte injury in females with Fabry disease.

BACKGROUND: Fabry disease. an X-linked deficiency of α-galactosidase A coded by the GLA gene, leads to intracellular globotriaosylceramide (GL-3) accumulation. Although less common than in males, chronic kidney disease, occurs in ∼ 15% of females. Recent studies highlight the importance of podocyte injury in Fabry nephropathy development and progression. We hypothesized that the greater the % of podocytes with active wild-type GLA gene (due to X-inactivation of the mutant copy) the less is the overall podocyte injury. METHODS: Kidney biopsies from 12 treatment-naive females with Fabry disease, ages 15 (8-63), median [range], years were studied by electron microscopy and compared with 4 treatment-naive male patients. RESULTS: In females, 51 (13-100)% of podocytes (PC) per glomerulus had no GL-3 inclusions, this consistent with a non-Fabry podocyte phenotype (NFPC). In PC with GL-3 inclusions [Fabry podocyte phenotype (FPC)], GL-3 volume density per podocyte was virtually identical in females and males, consistent with little or no cross-correction between FPC and NFPC. %NFPC per glomerulus (%NFPC/glom) correlated with age in females (r = 0.65, p = 0.02), suggesting a survival disadvantage for FPC over time. Age-adjusted %NFPC/glom was inversely related to foot process width (FPW) (r = -0.75, p = 0.007), an indicator of PC injury. GL-3 volume density in FPC in females correlated directly with FPW. CONCLUSIONS: These findings support important relationships between podocyte mosaicism and podocyte injury in female Fabry patients. Kidney biopsy, by providing information about podocyte mosaicism, may help to stratify females with Fabry disease for kidney disease risk and to guide treatment decisions.

The school nurse role in asthma management: can the action plan help?

Asthma is the most common chronic disorder in American schoolchildren, and school nurses play a valuable role in its management. A study was conducted in which school nurses were asked to describe their role in caring for students with asthma and their use of Asthma Action Plans (AAPs). The nurses indicated that they frequently provided direct care and education. They were comfortable with providing care to students with asthma and familiar with AAPs. Having an AAP increased their confidence in managing students with asthma. This emphasizes the need for continued education regarding the AAP and the development of policies that direct care and encourage use of an AAP at school.

Predictors of protocol adherence in a pediatric asthma clinical trial.

BACKGROUND: Declining protocol adherence can threaten the validity of a clinical trial. OBJECTIVE: We sought to explore patient and family factors important for protocol adherence in the 133 patients followed at one of the 8 Childhood Asthma Management Program (CAMP) clinical centers. Difficulties with timely return of diary cards (diary card problem), with keeping or frequently rescheduling appointments (appointment problem), and with commitment to all aspects of the trial (commitment problem) were tracked prospectively during the treatment phase of CAMP, which ranged from 20 to 40 months at the time of the analysis. METHODS: We performed a cross-sectional analysis. RESULTS: During the course of this investigation, no St Louis CAMP patients dropped out of the study, although signs of eroding participation were observed in 44% of patients. For this cross-sectional analysis, the percentage of patients exhibiting protocol-adherence problems was greater the longer patients had been in the trial: 33.3% at 20 to 25 months, 39.5% at 26 to 30 months, 51.4% at 31 to 35 months, and 69.2% at 36 to 40 months (P <.01). The diary card problem was present in 22.2% of the patients enrolled in the trial for 20 to 25 months compared with 66.7% for patients enrolled for 36 to 40 months (P <.005). Appointment and commitment problems were present in smaller percentages of patients and did not change by time in the trial (P =.41 and.22, respectively). A logistic regression analysis of demographic characteristics indicated that age at randomization and time in the trial were significant factors: for every 2-year increase in age, a child was twice as likely to have a commitment problem (odds ratio [OR], 1.96; 95% CI, 1.50-2.57), and for each additional 5 months of participation in the study, a child was twice as likely to have a diary card problem (OR, 1.91; 95% CI, 1.76-2.07). There was no influence of family income, patient race, or patient sex on the occurrence of any of the 3 protocol-adherence problems. A similar analysis of psychologic characteristics of the child and family indicated (1) a 2-fold increase in the risk of a diary card problem with a 10% increase in the percentage of total commissions on the attention scale of the Gordon Diagnostic Study (OR, 2.18; 95% CI, 2.02-2.35), (2) a 2-fold decrease in the risk of an appointment problem with a 10-unit increase in the Child Manifest Anxiety Scale (OR, 0.46; 95% CI, 0.44-0.49), (3) a 2-fold decrease in risk of an appointment problem with a 10-unit increase in the cohesion subscale of the Family Environment Scale (OR, 0.58; 95% CI, 0.55-0.60), and (4) a 5-fold decrease in the risk of a commitment problem with a 10-unit increase in the Child Depression Index score (OR, 0.21; 95% CI, 0.18-0.24). CONCLUSIONS: Adherence and retention problems commonly occur in longer clinical trials. CAMP patients and families were selected in part on the basis of likelihood of being able to participate in the trial to enhance the conclusions of the trial. Despite this selection process, adherence problems were noted. Problems increased with duration of participation, increasing child age, and the presence of less family cohesion or attention problems in the child. In contrast, the presence of mild emotional distress (anxiety and depression) in the child was associated with fewer protocol-adherence problems. Incorporating procedures that help anticipate and identify adherence problems early might improve continued participation in all aspects of a trial and even retention in long-term clinical trials.