Screening for haemoglobin disorders: One size may not fit all.

Accurate laboratory screening for sickle cell disease and other haemoglobin disorders is expanding worldwide. Two new reports describe different methods and strategies for screening in Mali and Denmark, respectively, and their encouraging results suggest that countries should tailor their screening programmes according to local needs, resources and opportunities. Commentary on: Guindo et al. Potential for a large-scale newborn screening strategy for sickle cell disease in Mali: a comparative diagnostic performance study of two rapid diagnostic tests (SickleScan® and HemotypeSC®) on cord blood. Br J Haematol 2024;204:337-345 and Gravholt et al. The Danish national haemoglobinopathy screening programme: report from 16 years of screening in a low-prevalence, non-endemic region. Br J Haematol 2024;204:329-336.

Measurement of plasma total calcium before plasma free ionized calcium - a possibility with affordable pitfalls.

Free ionized calcium (fCa) is considered the gold standard for assessing calcium status in patients, but it is relatively expensive and is associated with several preanalytical and analytical error sources. We investigated the feasibility of using a reflex test that involves first measuring total calcium (tCa) and if out of reference range, then measure fCa, with expectation of reducing the number of fCa measurements. We used data from 1815 unique patients with concurrent measurement of fCa, tCa and albumin adjusted calcium (aCa). Patients were stratified by albumin level, and the association of fCa to tCa and aCa respectively was assessed with linear regression. The regression analysis showed the best linearity for tCa and aCa at albumin <35 g/L (R2: 0.80-0.90), and the poorest at albumin >40 g/L (R2: tCa 0.58; aCa 0.59). We examined the accuracy of hypo- and hypercalcemia classifications for tCa, aCa and the reflex test. aCa had more misclassifications of hypo- and hypercalcemia than tCa, with respectively 25% and 21%. Implementation of the reflex test would correct any false hypo- or hypercalcemia classified by tCa, leaving only false negative results corresponding to 9% of all tCa measurements. False negative results were on average 0.04 mmol/L above or below the reference range of fCa. Implementation of the reflex test reduces the number of fCa by 68% without major errors diagnosing hyper- or hypocalcemia.

New HIV infections from blood transfusions averted in 28 countries supported by PEPFAR blood safety programs, 2004-2015.

BACKGROUND: To quantify the impact of the US President's Emergency Plan for AIDS Relief (PEPFAR) on the risk of HIV transmission through infected blood donations in countries supported by PEPFAR blood safety programs. METHODS: Data reported to the World Health Organization Global Database on Blood Safety were analyzed from 28 countries in sub-Saharan Africa (SSA), Asia, and the Caribbean during 2004-2015. We used the Goals model of Spectrum Spectrum System Software, version 5.53, to perform the modeling, assuming laboratory quality for HIV testing had 91.9% sensitivity and 97.7% specificity irrespective of testing method based on results of two external quality assurance and proficiency testing studies of transfusion screening for HIV in SSA blood centers. We calculated the number of new HIV infections from the number of transfusions and the prevalence of HIV infection acquired from blood transfusions with infected blood donations. We determined the impact of laboratory testing programs by estimating the number of new HIV infections averted since PEPFAR implementation. RESULTS: Assuming that HIV testing would not be performed in any of these countries without PEPFAR funding, the number of new HIV infections acquired from blood transfusions averted by laboratory testing increased over time in all 28 countries. The total number of HIV infections averted was estimated at 229 278 out of 20 428 373 blood transfusions during 2004-2015. CONCLUSION: Our mathematical modeling suggests a positive impact achieved over 12 years of PEPFAR support for blood safety. Standardized HIV testing of donated blood has reduced the risk of HIV transmission through blood transfusions in SSA, Asia, and the Caribbean.

Clinical versus laboratory screening for sexually transmitted infections prior to insertion of intrauterine contraception among women living with HIV/AIDS: a randomized controlled trial.

STUDY QUESTION: Does laboratory testing after syndromic screening for sexually transmitted infections (STIs) reduce the rate of intrauterine contraception (IUC) removal among women living with HIV/AIDS (WLHA)? SUMMARY ANSWER: Additional laboratory testing after syndromic screening for STIs did not affect the likelihood that a woman would remove an IUC immediately or within 1 year of IUC use or the frequency of post-insertion unscheduled clinic visits. In low-risk WLHA, the incidence rate of IUC removal is low with or without laboratory testing. WHAT IS KNOWN ALREADY: Fear of infectious morbidity remains an obstacle to uptake of IUC by WLHA. The value of laboratory testing after syndromic screening for STI before the insertion of IUC remains uncertain. STUDY DESIGN, SIZE, DURATION: We enrolled WLHA from 2 September to 6 December 2013 and followed them up to 31 December 2014. After syndromic screening, 703 women free of STIs were randomized to either additional laboratory screening or no additional screening for STI before IUC insertion. The randomization sequence was generated by an independent statistician and randomization numbers placed in opaque sequentially numbered sealed envelopes. All women randomized had an IUC inserted and in all 672 participants completed the 1-year follow-up. The study staff who followed up the participants were blinded to the study allocation groups. Incidence rate ratios (IRRs) were used to compare the incidence rates of IUC removal, unscheduled clinic attendance and IUC continuation between the two groups. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women eligible to participate were 18-49 years old at study entry, in a relationship with a male partner, wanted to avoid pregnancy for at least 1 year and were undergoing HIV/AIDS care at Mulago Hospital, Uganda. Participants completed a baseline questionnaire and up to four follow-up questionnaires until discontinuation of IUC, loss to follow-up or end of study observation after 12 months. MAIN RESULTS AND THE ROLE OF CHANCE: The rate of IUC removal was 8.8% (29/331) in the no additional screening group and 8.0% (27/341) in the additional laboratory screening group [IRR 1.1 (95% CI 0.63-1.93)]. Unscheduled clinic attendances were similar in the two groups at 1 year of IUC insertion: 13.6% (45/331) in the no additional screening group and 12.3% (42/241) in the additional laboratory screening group. During the 1-year follow-up, only five women, three from the no additional screening group and two from the additional laboratory screening group, developed pelvic inflammatory disease (PID), as defined by established diagnostic criteria. LIMITATIONS, REASONS FOR CAUTION: We were not able to carry out STI risk assessment directly from the men thus women with high-risk partners could have been included in the study and this may be responsible for the lack of a demonstrable effect of additional laboratory screening on incidence rates of IUC removals and unscheduled clinic attendance. The diagnosis of PID was based on clinical signs and symptoms; therefore, subclinical PID could have been missed. WIDER IMPLICATIONS OF THE FINDINGS: Among WLHA, the incidence rate of IUC removal is low and IUC continuation high. Syndromic screening for STIs could be sufficient in indentifying WLHA who are suitable for IUC use. However, our findings are only generalizable to women in HIV/AIDS care who have access to good follow-up. STUDY FUNDING/COMPETING INTERESTS: The study was supported by Medical Education for Equitable Services to all Ugandans, a Medical Education Partnership Initiative grant number 5R24TW008886 from the office of Global AIDS Coordinator and the US Department of Health and Human Services, Health Resources and Services Administration and National Institutes of Health. Additional funding was from the Swedish International Development Agency, Swedish Research Council (SIDA/VR). The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: This trial was registered at Pan African Clinical Trial, Registry. PACTR 201308000561212.

Screening the mechanical stability of Escherichia coli biofilms through exposure to external, hydrodynamic shear forces.

The desire to attain a deeper understanding of the fundamental aspects governing the mechanical properties of biofilms has become more prominent in recent years. This has largely been due to the realization that these sessile microbial communities often withstand environments where hydrodynamic turbulence and shearing forces are considerable. In the present study, Escherichia coli K-12 was used as a model system to develop a laboratory technique that can be used to quickly screen the mechanical integrity or stability of laboratory cultivated bacterial biofilms when exposed to such external, hydrodynamic shear forces. The screening method utilizes a custom-built, automated water jetting apparatus to generate and precisely apply a pressurized stream of water directly to biofilms cultured in multi-well plates. An optimized set of water jetting parameters was determined to resolve subtle to moderate differences in the mechanical stability of isogenic strains of E. coli K-12 as a function of percent biofilm removal. Mutations in both flagella biosynthesis (fliA) and acetate metabolism (ackA and ackA pta) were shown to impair the mechanical integrity of 24-h biofilms, while a "housekeeping" strain deficient in arginine metabolism (argD) exhibited a mechanical stability profile comparable to the parent strain.

Implementation of Provider-Focused Education to Improve Laboratory Screening for Pediatric Patients With Elevated Body Mass Index in Primary Care: A Quality Improvement Project.

INTRODUCTION: Children with elevated body mass index (BMI) do not consistently receive recommended laboratory screenings. This project aimed to increase provider screening rates and knowledge of screening guidelines for this population. METHOD: This project utilized the Rosswurm and Larrabee evidence-based practice model. Providers completed education with pretest and posttest design. Laboratory screening rates were measured with retrospective chart reviews, and a project satisfaction survey was conducted. RESULTS: Nine (82%) of 11 providers showed an increase in knowledge of screening for children with elevated BMI. Laboratory screening increased (27% to 39%) above the preintervention median (25%) for children with obesity and was above the median (22%) for one month of the project (15% to 26%) for children with overweight. CONCLUSIONS: Project results suggest education improved knowledge and compliance with guidelines for laboratory screening of children with an elevated BMI. Asynchronous education and sharing of compliance rates are adaptable to similar quality improvement projects.

Infectious disease screening in a dedicated primary care clinic for children in foster care.

BACKGROUND: Children in foster care are considered at high risk for infectious diseases, and guidelines recommend screening for tuberculosis, hepatitis B and C, syphilis, gonorrhea and chlamydia. Little is known about the prevalence of infectious disease in children in foster care. OBJECTIVES: Describe infectious disease screening practices in a primary care clinic dedicated to caring for children in foster care. PARTICIPANTS AND SETTING: Patients evaluated at a foster care primary care clinic at a southwestern academic center. METHODS: Retrospective chart review. RESULTS: From January 1, 2017 through December 31, 2018, 2868 unique patients were evaluated (53 % male, 41 % white, 30 % black, 19 % Hispanic); 1638 (57 %) had any infectious disease laboratory screening done. About 50 % of children had completed screens for tuberculosis, HIV, syphilis and hepatitis C. Tuberculosis screens were positive in 3.6 % of children, 5.5 % of adolescents were positive for chlamydia and <1 % of children were positive for HIV, syphilis or hepatitis C. Increasing age and number of visits were associated with completed tuberculosis, HIV, syphilis and hepatitis C screenings (p < 0.01); female adolescents with completed labs were more likely to be screened for gonorrhea and chlamydia than male adolescents. CONCLUSIONS: Few positive infectious disease screenings were identified in children evaluated in a dedicated foster care primary care clinic despite presence of risk factors. Multiple visits to a primary care foster care clinic may increase the likelihood of completed screenings. Targeted infectious disease screening based on age and local epidemiology may be less traumatizing but still clinically appropriate.

Colonization and Authentication of the Pyrethroid-Resistant Anopheles gambiae s.s. Muleba-Kis Strain; an Important Test System for Laboratory Screening of New Insecticides.

BACKGROUND: The emergence and spread of insecticide resistance in malaria vectors to major classes of insecticides call for urgent innovation and application of insecticides with novel modes of action. When evaluating new insecticides for public health, potential candidates need to be screened against both susceptible and resistant mosquitoes to determine efficacy and to identify potential cross-resistance to insecticides currently used for mosquito control. The challenges and lessons learned from establishing, maintaining, and authenticating the pyrethroid-resistant An. gambiae s.s. Muleba-Kis strain at the KCMUCo-PAMVERC Test Facility are described in this paper. METHODS: Male mosquitoes from the F1 generation of wild-pyrethroid resistant mosquitoes were cross-bred with susceptible female An. gambiae s.s. Kisumu laboratory strain followed by larval selection using a pyrethroid insecticide solution. Periodic screening for phenotypic and genotypic resistance was done. WHO susceptibility tests and bottle bioassays were used to assess the phenotypic resistance, while Taqman™ assays were used to screen for known target-site resistance alleles (kdr and ace-1). Additionally, the strains were periodically assessed for quality control by monitoring adult weight and wing length. RESULTS: By out-crossing the wild mosquitoes with an established lab strain, a successful resistant insectary colony was established. Intermittent selection pressure using alphacypermethrin has maintained high kdr mutation (leucine-serine) frequencies in the selected colony. There was consistency in the wing length and weight measurements from the year 2016 to 2020, with the exception that one out of four years was significantly different. Mean annual wing length varied between 0.0142-0.0028 mm compared to values obtained in 2016, except in 2019 where it varied by 0.0901 mm. Weight only varied by approximately 0.001 g across four years, except in 2017 where it differed by 0.005 g. Routine phenotypic characterization on Muleba-Kis against pyrethroids using the WHO susceptibility test indicated high susceptibility when type I pyrethroids were used compared to type II pyrethroids. Dynamics on susceptibility status also depended on the lapse time when the selection was last done. CONCLUSIONS: This study described the procedure for introducing, colonizing, and maintaining a resistant An. gambiae s.s. strain in the laboratory with leucine to serine substitution kdr allele which reflects the features of the wild-resistant population in East Africa. Challenges in colonizing a wild-resistant mosquito strain were overcome by out-crossing between mosquito strains of desired traits followed by intermittent insecticide selection at the larval stage to select for the resistant phenotype.

The Experience of 2 Independent Schools With In-Person Learning During the COVID-19 Pandemic.

BACKGROUND: In 2020, US schools closed due to SARS-CoV-2 but their role in transmission was unknown. In fall 2020, national guidance for reopening omitted testing or screening recommendations. We report the experience of 2 large independent K-12 schools (School-A and School-B) that implemented an array of SARS-CoV-2 mitigation strategies that included periodic universal testing. METHODS: SARS-CoV-2 was identified through periodic universal PCR testing, self-reporting of tests conducted outside school, and contact tracing. Schools implemented behavioral and structural mitigation measures, including mandatory masks, classroom disinfecting, and social distancing. RESULTS: Over the fall semester, School-A identified 112 cases in 2320 students and staff; School-B identified 25 cases (2.0%) in 1400 students and staff. Most cases were asymptomatic and none required hospitalization. Of 69 traceable introductions, 63 (91%) were not associated with school-based transmission, 59 cases (54%) occurred in the 2 weeks post-thanksgiving. In 6/7 clusters, clear noncompliance with mitigation protocols was found. The largest outbreak had 28 identified cases and was traced to an off-campus party. There was no transmission from students to staff. CONCLUSIONS: Although school-age children can contract and transmit SARS-CoV-2, rates of COVID-19 infection related to in-person education were significantly lower than those in the surrounding community. However, social activities among students outside of school undermined those measures and should be discouraged, perhaps with behavioral contracts, to ensure the safety of school communities. In addition, introduction risks were highest following extended school breaks. These risks may be mitigated with voluntary quarantines and surveillance testing prior to reopening.

The value of routine laboratory screening in the neonatal intensive care unit.

BACKGROUND: Healthcare spending is expected to grow faster than the economy over the next decade, and the cost of prematurity increases annually. The aim of this study was to investigate the frequency of intervention after routine laboratory testing in preterm infants. METHODS: This was a retrospective study of preterm infants (≤34 weeks) admitted to the NYU Langone Health NICU from June 2013 to December 2014. Data collected included demographics, results of laboratory tests, and resulting interventions. Intervention after a hemogram was defined as a blood transfusion. Intervention after a hepatic panel was defined as initiation or termination of ursodiol or change in dose of vitamin D. Subjects were stratified into 3 groups based on gestation (<28 weeks, 28-31 6/7 weeks, 32-34 weeks). Chi-square analysis was used to compare the frequency of intervention between the groups. RESULTS: A total of 135 subjects were included in the study. The frequency of intervention after a hemogram was 8.4% in infants <28 weeks, 4.6% in infants 28-31 6/7 weeks, and 0% in infants 32-34 weeks; this difference was found to be statistically significant (p = 0.02). The frequency of intervention after a hepatic panel was 4.2% in infants <28 weeks, 5.7% in infants 28-31 6/7 weeks, and 0% in infants 32-34 weeks, which was not found to be a statistically significant different. CONCLUSION: No interventions were undertaken post-routine laboratory testing in any infant 32-34 weeks and routine testing in this population may be unnecessary. Further studies are needed to elucidate if routine testing affects neonatal outcomes.

TyG-er: An ensemble Regression Forest approach for identification of clinical factors related to insulin resistance condition using Electronic Health Records.

BACKGROUND: Insulin resistance is an early-stage deterioration of Type 2 diabetes. Identification and quantification of insulin resistance requires specific blood tests; however, the triglyceride-glucose (TyG) index can provide a surrogate assessment from routine Electronic Health Record (EHR) data. Since insulin resistance is a multi-factorial condition, to improve its characterisation, this study aims to discover non-trivial clinical factors in EHR data to determine where the insulin-resistance condition is encoded. METHODS: We proposed a high-interpretable Machine Learning approach (i.e., ensemble Regression Forest combined with data imputation strategies), named TyG-er. We applied three different experimental procedures to test TyG-er reliability on the Italian Federation of General Practitioners dataset, named FIMMG_obs dataset, which is publicly available and reflects the clinical use-case (i.e., not all laboratory exams are prescribed on a regular basis over time). RESULTS: Results detected non-conventional clinical factors (i.e., uricemia, leukocytes, gamma-glutamyltransferase and protein profile) and provided novel insight into the best combination of clinical factors for detecting early glucose tolerance deterioration. The robustness of these extracted clinical factors was confirmed by the high agreement (from 0.664 to 0.911 of Lin's correlation coefficient (rc)) of the TyG-er approach among different experimental procedures. Moreover, the results of the three experimental procedures outlined the predictive power of the TyG-er approach (up to a mean absolute error of 5.68% and rc=0.666,p<.05). CONCLUSIONS: The TyG-er approach is able to carry information about the identification of the TyG index, strictly correlated with the insulin-resistance condition, while extracting the most relevant non-glycemic features from routine data.

Development of a novel automated screening method for detection of FVIII Inhibitors.

INTRODUCTION: Factor VIII activity is routinely determined by measuring the activated partial thromboplastin time (aPTT) of a patient plasma sample and determining percent activity from a standard curve. To maximize the detection of a clotting factor inhibitor, a subjective assessment of parallelism of a patient curve compared with a standard curve is performed. We developed and validated an automated objective method to assess parallelism as a rapid screening tool for detection of an inhibitor to factor VIII during routine FVIII assays. METHODS: We performed FVIII assays on a subset of FVIII-deficient patients with hemophilia A with and without inhibitors. Utilizing a ratio of the slopes from parallelism curves obtained by an independent Microsoft excel program in patients compared with a normal standard curve, we determined a cutoff ratio predictive for presence of an inhibitor. RESULTS: A cutoff ratio of patient to control slopes of <0.45 for the detection of an inhibitor to FVIII was 100% sensitive and 91.6% specific, with a positive predictive value of 92.3% and a negative predictive value of 100%. CONCLUSION: Utilizing a ratio of the slopes from parallelism curves in patients with and without an inhibitor, we developed and validated a rapid, automated, and objective method to assess parallelism as an added screening tool for detection of an inhibitor to factor VIII during routine FVIII assays on a STAGO-based coagulation platform. This simple automated method has the potential to detect inhibitors to other clotting factors.

Temporal trends in the diagnosis and management of childhood obesity/overweight in primary care.

OBJECTIVE: To determine the temporal trends in diagnosis and management of pediatric overweight/obesity by primary care providers at a single medical center. PATIENTS: Children 2 to 18 years old undergoing a general medical examination during 3 calendar years (2003, 2006, and 2009). The number of visits for general medical examination were 6390 in 2003, 6646 in 2006, and 7408 in 2009. METHODS: We performed a retrospective review of the electronic medical records for weight related diagnostic and/or management terms and laboratory screening in children with body mass index at or greater than the 85th percentile (n = 1630 in 2003, 1495 in 2006, and 1730 in 2009). RESULTS: There was a significant increase in the diagnosis of obesity among obese children seen in 2009 (53.3%) compared with 2006 (36%, P < .001) and 2003 (24.3%, P < .001). Weight-related counseling was documented in a higher proportion of obese children in 2009 (49.4%) compared with 2006 (34.8%) and 2003 (26.6%). There was a significant increase in counseling regarding screen time in 2009 compared with 2006. A significant increase in screening for nonalcoholic fatty liver disease was also noted (30.5% in 2009 vs 21.9% in 2006, P = .018). CONCLUSIONS: There has been steady improvement in the rates of obesity diagnosis and obesity-related counseling by primary care providers. However, continued efforts to increase awareness of these issues are needed as nearly half of obese children remained undiagnosed and recommended laboratory screening for obesity-related comorbidities was performed in only a third of obese children.

Tuberculosis-Diagnostic Expert System: an architecture for translating patients information from the web for use in tuberculosis diagnosis.

BACKGROUND: Over 1.5-2 million tuberculosis deaths occur annually. Medical professionals are faced with a lot of challenges in delivering good health-care with unassisted automation in hospitals where there are several patients who need the doctor's attention. OBJECTIVE: To automate the pre-laboratory screening process against tuberculosis infection to aid diagnosis and make it fast and accessible to the public via the Internet. The expert system we have built is designed to also take care of people who do not have access to medical experts, but would want to check their medical status. METHODS: A rule-based approach has been used, and unified modeling language and the client-server architecture technique were applied to model the system and to develop it as a web-based expert system for tuberculosis diagnosis. Algorithmic rules in the Tuberculosis-Diagnosis Expert System necessitate decision coverage where tuberculosis is either suspected or not suspected. The architecture consists of a rule base, knowledge base, and patient database. These units interact with the inference engine, which receives patient' data through the Internet via a user interface. RESULTS: We present the architecture of the Tuberculosis-Diagnosis Expert System and its implementation. We evaluated it for usability to determine the level of effectiveness, efficiency and user satisfaction. The result of the usability evaluation reveals that the system has a usability of 4.08 out of a scale of 5. This is an indication of a more-than-average system performance. CONCLUSION: Several existing expert systems have been developed for the purpose of supporting different medical diagnoses, but none is designed to translate tuberculosis patients' symptomatic data for online pre-laboratory screening. Our Tuberculosis-Diagnosis Expert System is an effective solution for the implementation of the needed web-based expert system diagnosis.

Implications of medical screenings of patients arriving for dental treatment: the results of a comprehensive laboratory screening.

BACKGROUND: The authors conducted medical laboratory screenings in a dental setting to determine the relationships between the laboratory test results and self-reported medical health findings. METHODS: The authors collected serum, urine and medical histories from 171 patients (116 [68 percent] women; mean age, 43.4 years) who arrived for dental treatment as a component of a clinical trial and performed complete blood cell counts, standard blood chemistry panels and urinalysis on the samples. RESULTS: The authors found 414 abnormal laboratory test results (an average of 2.42 per patient). Eighty-three percent of participants had one or more abnormal test results, 83 percent had abnormal test results and did not indicate a relevant disease in their medical history, and 18 percent had laboratory test results outside the 99 percent reference range (that is, > three standard deviations from the mean). Abnormal test results were significantly associated with sex, age, race and medical history (P< .05). Abnormal test results associated with kidney disease were related to patients with cardiovascular disease and diabetes, as well as those who tended to be on average older than 50 years. CONCLUSIONS: The high frequency of significant abnormal laboratory test results detected in this study suggests that many patients may be unaware of their medical statuses. PRACTICAL IMPLICATIONS: Abnormal laboratory test results are detected frequently in the serum and urine of patients arriving for dental treatment, which could indicate undiagnosed disease and less than optimal medical management.