Primary Health Care Laboratory Research Articles

AI-Supported Digital Microscopy Diagnostics in Primary Health Care Laboratories: Protocol for a Scoping Review.

Digital microscopy combined with artificial intelligence (AI) is increasingly being implemented in health care, predominantly in advanced laboratory settings. However, AI-supported digital microscopy could be especially advantageous in primary health care settings, since such methods could improve access to diagnostics via automation and lead to a decreased need for experts on site. To our knowledge, no scoping or systematic review had been published on the use of AI-supported digital microscopy within primary health care laboratories when this scoping review was initiated. A scoping review can guide future research by providing insights to help navigate the challenges of implementing these novel methods in primary health care laboratories. The objective of this scoping review is to map peer-reviewed studies on AI-supported digital microscopy in primary health care laboratories to generate an overview of the subject. A systematic search of the databases PubMed, Web of Science, Embase, and IEEE will be conducted. Only peer-reviewed articles in English will be considered, and no limit on publication year will be applied. The concept inclusion criteria in the scoping review include studies that have applied AI-supported digital microscopy with the aim of achieving a diagnosis on the subject level. In addition, the studies must have been performed in the context of primary health care laboratories, as defined by the criteria of not having a pathologist on site and using simple sample preparations. The study selection and data extraction will be performed by 2 independent researchers, and in the case of disagreements, a third researcher will be involved. The results will be presented in a table developed by the researchers, including information on investigated diseases, sample collection, preparation and digitization, AI model used, and results. Furthermore, the results will be described narratively to provide an overview of the studies included. The proposed methodology is in accordance with the JBI methodology for scoping reviews. The scoping review was initiated in January 2023, and a protocol was published in the Open Science Framework in January 2024. The protocol was completed in March 2024, and the systematic search will be performed after the protocol has been peer reviewed. The scoping review is expected to be finalized by the end of 2024. A systematic review of studies on AI-supported digital microscopy in primary health care laboratories is anticipated to identify the diseases where these novel methods could be advantageous, along with the shared challenges encountered and approaches taken to address them. PRR1-10.2196/58149.

How to compare point-of-care testing results with hospital laboratory results: Recommendations for primary healthcare laboratories

How to compare point-of-care testing results with hospital laboratory results: Recommendations for primary healthcare laboratories

Diagnosis of soil-transmitted helminth infections with digital mobile microscopy and artificial intelligence in a resource-limited setting.

Infections caused by soil-transmitted helminths (STHs) are the most prevalent neglected tropical diseases and result in a major disease burden in low- and middle-income countries, especially in school-aged children. Improved diagnostic methods, especially for light intensity infections, are needed for efficient, control and elimination of STHs as a public health problem, as well as STH management. Image-based artificial intelligence (AI) has shown promise for STH detection in digitized stool samples. However, the diagnostic accuracy of AI-based analysis of entire microscope slides, so called whole-slide images (WSI), has previously not been evaluated on a sample-level in primary healthcare settings in STH endemic countries. Stool samples (n = 1,335) were collected during 2020 from children attending primary schools in Kwale County, Kenya, prepared according to the Kato-Katz method at a local primary healthcare laboratory and digitized with a portable whole-slide microscopy scanner and uploaded via mobile networks to a cloud environment. The digital samples of adequate quality (n = 1,180) were split into a training (n = 388) and test set (n = 792) and a deep-learning system (DLS) developed for detection of STHs. The DLS findings were compared with expert manual microscopy and additional visual assessment of the digital samples in slides with discordant results between the methods. Manual microscopy detected 15 (1.9%) Ascaris lumbricoides, 172 (21.7%) Tricuris trichiura and 140 (17.7%) hookworm (Ancylostoma duodenale or Necator americanus) infections in the test set. Importantly, more than 90% of all STH positive cases represented light intensity infections. With manual microscopy as the reference standard, the sensitivity of the DLS as the index test for detection of A. lumbricoides, T. trichiura and hookworm was 80%, 92% and 76%, respectively. The corresponding specificity was 98%, 90% and 95%. Notably, in 79 samples (10%) classified as negative by manual microscopy for a specific species, STH eggs were detected by the DLS and confirmed correct by visual inspection of the digital samples. Analysis of digitally scanned stool samples with the DLS provided high diagnostic accuracy for detection of STHs. Importantly, a substantial number of light intensity infections were missed by manual microscopy but detected by the DLS. Thus, analysis of WSIs with image-based AI may provide a future tool for improved detection of STHs in a primary healthcare setting, which in turn could facilitate monitoring and evaluation of control programs.

Using three external quality assurance schemes to achieve equivalent international normalized ratio results in primary and secondary healthcare

Accurate prothrombin time international normalized ratio (INR) results are essential for safe anticoagulation treatment. Patients are treated both in primary and secondary healthcare, therefore equivalence of INR results from point-of-care (POC) and hospital measurement procedures (MPs) are important. It is not possible to evaluate this equivalence in traditional external quality assessment (EQA). The aim of this paper is to describe a special quality assurance system consisting of three different EQA schemes to monitor the harmonization of INR results in Norway. The EQA scheme for hospital laboratories uses commutable control materials and evaluates participant performance and the equivalence of hospital MPs. The EQA scheme for primary healthcare laboratories uses non-commutable control materials and evaluates participant performance. A third EQA scheme for selected primary healthcare laboratories uses native patient split samples and evaluates the equivalence between POC and hospital MPs. The relationship between the three EQA schemes ispresented. The split sample EQA scheme provides a link between the hospital scheme and the scheme for primary healthcare. Results from 2017 to 2022 are presented for all three schemes. When aberrant EQA results occur Noklus takes actions to be able to have a sustainable equivalence between INR results. All three EQA schemes are important for monitoring the harmonization of INR results in Norway. This quality assurance system, including help and guidance of the participants, will reduce the risk of harm to patients due to non-equivalence of results from different MPs.

Assessing CD4 rejections across a national laboratory service for 2018 in South Africa: highlighting the importance of adherence to national handbook guidelines.

The National Health Laboratory Service as the preferred pathology service provider for the public health sector in South Africa, developed a national laboratory handbook to improve the clinic-laboratory-interface. A separate primary health care laboratory handbook was developed as part of the ideal clinic initiative by the National Department of Health. This study aimed to assess adherence to these guidelines using CD4 rejections the indicator. The retrospective crosssectional study design was used to analyse national laboratory data for the period from January to December 2019. Data were analysed using SAS 9.4. Lookup tables assigned the origin (health facility/laboratory), rejection reason, and sub-reason based on the populated rejection description that was captured in the laboratory information system. The rejection rate [RR = (rejections/total volume) ´ 100] was reported at the national, provincial and district levels. There were 85,378 rejections reported for 2,844,242 tests (RR 3.0%). Data was reported for 4136 health facilities across nine provinces. The RR was higher for an origin defined as health facility (2.9%) than laboratories (0.1%). The most common rejection reason was unsuitable specimen received (RR=2.3%), representing 75% of all rejections. This rejection criteria included using the incorrect anticoagulant, clotted sample and haemolysis. The provincial RR ranged from 2.2% to 4.0%. Three districts had an elevated RR ≥6% (organisational cut-off set at RR ≤5%). This study demonstrated the value of laboratory data to assess specimen rejections and identify causes to facilitate targeted training.

Medical laboratory accreditation in a resource-limited district health centre laboratory, Addis Ababa, Ethiopia.

BackgroundImproving the quality of medical laboratory services is a high priority in many countries. However, quality management systems for laboratories in resource-limited settings are often inadequate.ObjectivesThis article shares the experiences, benefits and challenges of the laboratory journey towards accreditation in a primary healthcare laboratory in Addis Ababa, Ethiopia.MethodsA retrospective review of laboratory records in Addis Ketema Health Center was conducted from 2012 to 2015. The study was supplemented by observations from some of the authors of this article who worked in the laboratory.ResultsThe laboratory journey towards accreditation began with a baseline assessment in 2012 using the World Health Organization African Region Stepwise Laboratory Quality Improvement Process Towards Accreditation; the baseline score was 78 points (0 stars). After mentorship support, the laboratory improved to 198 points (3 stars) in 2013 and 249 points (5 stars) in 2014. The laboratory scaled up to International Organization for Standardization 15189 requirements and received limited-scope accreditation for tuberculosis sputum microscopy and hematology tests in 2015. After adopting and implementing the standards, steady improvement was observed in the reliability of the laboratory services. Lack of resources was the major challenge the laboratory encountered.ConclusionEven though a remarkable quality performance improvement was observed over the entire process, inadequate skilled personnel was the major challenge identified in the road towards accreditation. Therefore, an appropriate, workload-based staffing structure should be developed to improve and sustain medical laboratory quality standards in resource-limited settings.

How well do Croatian laboratories adhere to national recommendations for laboratory diagnostics of chronic kidney disease (CKD)?

Background In 2014, the Joint Croatian Working Group (JCWG) for laboratory diagnostic of chronic kidney disease (CKD) conducted a survey across medical-biochemistry laboratories which demonstrated a large heterogeneity in this area of laboratory medicine. To ensure the tools for the standardization process, in 2017 the JCWG-CKD published the first Croatian recommendations for laboratory diagnostics of CKD. To assess the implementation process, we have repeated a survey to explore how well laboratories adhere to the recommendations. Methods An invitation to the survey was sent to all Croatian medical-biochemistry laboratories (n = 196). The questionnaire was designed in a form of 19 questions and statements, with possible multiple answers. Results The response rate was 98/196 (50.0%). The predominant method for serum creatinine measurement was the standardized compensated Jaffe method (79.2%). There was substantial decrease in the number of laboratories which measure creatinine with the non-standardized uncompensated Jaffe method, compared with the initial 2014 assessment; 7% vs. 40%, respectively. The number of the laboratories that did not report estimated glomerular filtration rate (eGFR) values decreased almost by half compared to the initial data (37.6% vs. 74.4%). However, compared to the 2014 initial assessment, a similar number of laboratories (54/98 vs. 58/80) did not measure urine albumin or protein. Conclusions The collected data showed a substantial improvement in the standardization of the serum creatinine measurement, as well as in the reporting of eGFR. However, albuminuria or proteinuria assessment is still not implemented nationwide, mainly in primary health care laboratories. This demonstrates the importance of promoting and monitoring implementation of guidelines after publication.

Harmonization activities of Noklus – a quality improvement organization for point-of-care laboratory examinations

Noklus is a non-profit quality improvement organization that focuses to improve all elements in the total testing process. The aim is to ensure that all medical laboratory examinations are ordered, performed and interpreted correctly and in accordance with the patients' needs for investigation, treatment and follow-up. For 25 years, Noklus has focused on point-of-care (POC) testing in primary healthcare laboratories and has more than 3100 voluntary participants. The Noklus quality system uses different tools to obtain harmonization and improvement: (1) external quality assessment for the pre-examination, examination and postexamination phase to monitor the harmonization process and to identify areas that need improvement and harmonization, (2) manufacturer-independent evaluations of the analytical quality and user-friendliness of POC instruments and (3) close interactions and follow-up of the participants through site visits, courses, training and guidance. Noklus also recommends which tests that should be performed in the different facilities like general practitioner offices, nursing homes, home care, etc. About 400 courses with more than 6000 delegates are organized annually. In 2017, more than 21,000 e-learning programs were completed.

Evaluation of Laboratory Biosafety in Khartoum State Primary Health Care Centers, Sudan

Background: This study was designed to assess the biosafety precautions in primary care health centers in Khartoum state. Diagnostic laboratories in seven localities were selected by stratified simple random sampling technique was assessed by using a designed questionnaire and a check list. Results: Among 33 laboratories, 0 (0.0%) were appointing a biosafety officer. 0 (0.0%) supplied with an alarm system, have trained personnel, and have fire exit. Provision of personnel protection, 12 (36.4%), always wearied laboratory coat, 6 (18.2%) personnel used gloves with every procedure, 25 (75.8%) washed their hands regularly. All laboratories, 33 (100%) have cleaning personnel, and in 21 (63.3%) removal of infectious material waste was done daily. Vaccination program for hepatitis and tuberculosis were identified in 16 (48.5%) of the laboratories. Conclusion: There is a great need to establish and implement biosafety precautions program in governmental reference primary health care laboratories.

Reference Intervals of Reticulated Platelets and Other Platelet Parameters and Their Associations

Reticulated platelets are platelets recently released from the bone marrow, and they can serve as a noninvasive indicator of recent megakaryopoietic activity. Widespread clinical use has been hampered by laborious methods and lack of standardization. Recently, a fully automated method was released on the Abbott CELL-DYN Sapphire hematology analyzer. To establish reference ranges for reticulated platelets. Secondary aims were to investigate associations between reticulated platelets and other platelet parameters like mean platelet volume, plateletcrit, and platelet distribution width. Reticulated platelets and other platelet parameters were measured in an unselected cohort of 8089 subjects visiting a primary health care laboratory. The reticulated platelet data were analyzed using the Bhattacharya technique. In addition, a nonparametric method was used in selected subjects with normal platelet counts for providing reference ranges. Reticulated platelets ranged from 0.4% to 6.0% or from 1 to 18 × 10(3)/μL. Reticulated platelets increased significantly with the subjects' age. Statistically, males had slightly higher values than females, but the differences were negligible. Reticulated platelets were positively correlated with platelet count and negatively with mean platelet volume. Reference ranges have been established for reticulated platelets as measured on the CELL-DYN Sapphire hematology analyzer. There were no relevant differences between the sexes, but there was a clear effect of age. An individual's reticulated platelets are associated with the platelet count as well as mean platelet volume.

Reference intervals of extended erythrocyte and reticulocyte parameters

Optical analysis of erythrocytes can provide information on the hemoglobin concentration and content of reticulocytes and mature erythrocytes. Such parameters have proven clinical utility in anemia diagnosis and therapy monitoring. For interpretation, reliable reference ranges are needed. The aim of this study was to establish reference intervals for extended erythrocyte and reticulocyte parameters as measured with the Abbott CELL-DYN Sapphire hematology analyzer. Secondary aims were to study sample stability and to investigate gender- and age dependency of the reference ranges. Extended RBC parameters were measured in routine samples of a primary health care laboratory. The study cohort included 8161 samples of unique individuals, which were analyzed using Bhattacharya statistics. As a comparison, reference intervals were calculated in a subset of individuals without iron depletion. The majority of erythrocyte and reticulocyte parameters were normally distributed, allowing calculation of reference intervals. Only for hypo- and hyperchromic erythrocytes non-parametric statistics had to be used. The reference range for mean cellular hemoglobin content of reticulocytes (MCHr) was 28.5-34.5 pg (1.77-2.14 fmol) in the entire study group and 26.0-35.1 pg (1.60-2.17 fmol) in the non iron-depleted subgroup. No differences between sexes were found. Most parameters showed significant age effects in children and adolescents. Reference intervals have been established for extended RBC and reticulocyte parameters for the CELL-DYN Sapphire. Gender effects could not be demonstrated and age effects were of limited size, except for individuals younger than 18 years. Extended RBC parameters are stable for at least 6 h after blood collection.

Value of Additional CD19 Lymphocyte Counts for the Detection of B-CLL in a Primary Health Care Laboratory

Background: B-cell chronic lymphocytic leukaemia (B-CLL) is the most common type of lymphoma in the Western world and is often diagnosed by coincidence in patients with an increased absolute lymphocyte count (ALC). Although immunophenotyping is advised for all patients with an increased ALC of unknown aetiology, referral for immunophenotyping in all patients with increased ALC will result in high costs and inconvenience for patients, since a considerable number of patients with increased ALC has no B-CLL or other malignancy. On the other hand, early haematological consultation at diagnosis is becoming more important, since initiation of treatment of B-CLL is changing from a symptom-based strategy towards a strategy based on biological markers. In this context, an additional CD19 count might be a valuable laboratory test to reduce unnecessarily referrals and to facilitate early haematological consultation of patients with B-CLL.Aim: To investigate the value of an additional CD19 count in detecting B-CLL in patients with increased ALC in a primary care laboratory.Methods: In the period from March 2001 until October 2006, a CD 19 lymphocyte count was performed in all patients, living in a previously defined geographic area, aged ≥ 40 years with an abnormal White Blood Cell count (WBC), defined as absolute lymphocyte count (ALC) ≥ 6.0x109 cells/L, relative lymphocyte count (RLC) ≥ 60% or atypical lymphocytes (AL) ≥ 2+. WBC's were requested by general practitioners for any reason not further specified. Patients with positive EBV or CMV serology were excluded. CD19 lymphocyte counts were classified as negative (<1.0x109/L) or positive (≥1.0x109/L). In case of a positive test, referral to a haematologist was advised. A geographic area in which the contingency areas of SALTRO and the referral hospitals overlapped was based on postal codes in order to link patients in whom a CD19 lymphocyte count was performed to newly diagnosed B-CLL patients in the hospitals. In October 2007, all cases of B-CLL in this area were identified by a stepwise search-strategy with a survey among general practitioners, including two postal questionnaires and a telephone reminder and by consultation of three different databases. All data were collected anonymously and CD19 lymphocyte count cases and B-CLL cases were cross-referenced by postal code and date of birth.Results: A CD19 lymphocyte count was performed in 543 patients of 199,108 (0.3%) patients in whom a WBC was performed; 229 (42%) were positive and 314 (58%) were negative. In total, 120 patients with a B-CLL were identified; 119 in the positive test group en 1 in the negative group. This resulted in a sensitivity and Positive Predictive Value (PPV) of 99% (95%CI 97.9–99.7) and 52% (95%CI 47.6–56.2) respectively and specificity and Negative Predictive Value (NPV) of 74% (95%CI 70.1–77.7) and 100% (95%CI 98.7–100) respectively. This resulted in a Number Needed to Screen (NNS) of 1.9. The AUC for CD19 count and ALC, 0.92 (95% CI 0.90–0.94), was significantly higher than the AUC for ALC only; 0.85 (95% CI 0.81–0.88). The PPV of ALC only, 34% (118/348) was significantly lower compared to the PPV of the CD19 count and ALC combined; 52% (119/229).Conclusion: CD19 count is a valuable laboratory test in detecting B-CLL in a primary care setting with a high sensitivity and PPV. The CD19 count is superior to ALC only. Introduction of a CD19 count in a primary health care laboratory has additional value in the selection of patients with increased ALC for referral to haematologists. The value of early detection strategies for B-CLL, such as CD19 counts in a primary health laboratory, will depend on the outcome of ongoing studies of treatment, based on new biological markers indicative of a poor prognosis, in early stages of B-CLL.

Sputum Smear Microscopy: Evaluation of Impact of Training, Microscope Distribution, and Use of External Quality Assessment Guidelines for Resource-Poor Settings

Sputum smear microscopy is the main and often only laboratory technique used for the diagnosis of tuberculosis in resource-poor countries, making quality assurance (QA) of smear microscopy an important activity. We evaluated the effects of a 5-day refresher training course for laboratory technicians and the distribution of new microscopes on the quality of smear microscopy in 13 primary health care laboratories in Kinshasa, Democratic Republic of Congo. The 2002 external QA guidelines for acid-fast bacillus smear microscopy were implemented, and blinded rechecking of the slides was performed before and 9 months after the training course and microscope distribution. We observed that the on-site checklist was highly time-consuming but could be tailored to capture frequent problems. Random blinded rechecking by the lot QA system method decreased the number of slides to be reviewed. Most laboratories needed further investigation for possible unacceptable performance, even according to the least-stringent interpretation. We conclude that the 2002 external QA guidelines are feasible for implementation in resource-poor settings, that the efficiency of external QA can be increased by selecting sample size parameters and interpretation criteria that take into account the local working conditions, and that greater attention should be paid to the provision of timely feedback and correction of the causes of substandard performance at poorly performing laboratories.

Developing external quality assessment programmes for primary health: care level in resource limited countries

Laboratory services are an essential component of health care delivery in tropical countries and play a vital role in improving the accuracy of clinical diagnosis and the investigation of disease outbreaks. In developing countries, laboratories face numerous constraints to providing quality services, including poor selection of techniques, difficulties in equipment availability and maintenance, and shortages of supplies, staffing and supervision. Currently in the eastern African countries (Kenya, Tanzania and Uganda), internal quality control procedures are inconsistently carried out in most laboratories. National External Quality Assessment Schemes (EQAS) have been established in all countries addressing a limited number of tests, but are constrained by difficulties of sustainability and poor coverage. The Laboratory Programme of the African Medical and Research Foundation (AMREF) has been operating a simple EQAS for primary heath care laboratories since 1993. Tests addressed are those carried out in primary health care laboratories in eastern Africa. A total of 81 laboratories from 5 countries in the eastern African region have participated in the scheme since 1993 and 9 distributions were submitted since the start of the scheme. No laboratory participated in all distributions; 24 (30%) laboratories participated in 4 or more distributions. Of these, the hospital laboratories in Kenya and Tanzania showed improved average mean scores between the first two and subsequent distributions. The educational benefit of participation in the scheme is emphasised. There was an overall low rate of participation of laboratories (35%) once the scheme was expanded to include laboratories outside direct AMREF project activities. Contributing factors include shortages of staff and lack of time in busy rural laboratories, together with difficulties in communication; however, the voluntary nature and lack of appreciation of the benefits of participation may also play a role. To increase participation in the scheme and to address the quality of laboratory services throughout the region, AMREF is currently developing a Regional EQAS in collaboration with the Ministries of Health of Kenya, Tanzania and Uganda, in affiliation with the World Health Organisation (WHO). The approaches used to establish reference values for haemoglobin samples are discussed. The scheme has also been utilised to examine the performance of different techniques for haemoglobin estimation, demonstrating the inaccuracy of the visual comparator methods.

Evaluation of two methods for improving quality of diagnosis of bacteriuria by culture in primary healthcare

This study evaluates the effect of training on the results from Uricult Trio® and an established urine culture when used at primary healthcare laboratories in two Swedish counties, Uppsala and Värmland. Urine cultures and dipslides, Uricult Trio®, performed at these laboratories were interpreted a second time at central laboratories. Interpretation errors at the primary healthcare laboratories were calculated. Primary healthcare laboratories also received external control panels with urine cultures and dipslides. There was one study period each year for 3 years in Uppsala and for 2 years in Värmland. A training programme was completed between study periods in Värmland. In Uppsala, primary healthcare laboratory results could be reviewed, as interpretations by the central laboratory were returned to them. The main outcome measures were the percentage of interpretation errors which, in the first study period, was 33-39%. This dropped to 15-19% in the second study period. In the results from the external control panels there were no striking differences between the studied areas and Sweden as a whole, except that Uppsala showed a better result in reporting E. coli and failed in 10% compared to Sweden 46%. A method for both quality assessment and education is to ask the primary healthcare laboratories to send cultures to the central laboratory for interpretation requesting their return to the primary healthcare laboratory with the interpretation from the central laboratory attached.

Performance of Uricult Trio assessed by a comparison method and external control panels in primary healthcare

Using the comparison method, we have evaluated the technical performance of Uricult Trio® by culturing on Uricult Trio® and agar plates. Urine samples (477) from patients in primary healthcare were cultured in parallel in a microbiology laboratory. The result for Uricult Trio® evaluated using the comparison method was incorrect in 32% of the cultures. We also studied the performance of Uricult Trio® when used in primary healthcare by using external control panels. External control panels consisting of Uricult Trio®, inoculated with known concentrations of certain bacterial strains, were used to assess the performance of Uricult Trio® in primary healthcare during the period 1993-7. Aberrations in reports of concentration have ranged from 10% to 33%, failure in reporting of mixed culture from 0% to 91% and reporting of E. coli from 15% to 86%. There has been no sign of improvement over the years. The results indicate that Uricult Trio® is unsuitable for indications other than exclusion of urinary tract infection or diagnosis of urinary tract infection caused by E. coli. Further, there is need for quality assurance and training activities at primary healthcare laboratories, probably best carried out in collaboration with local clinical microbiology laboratories.

Laboratory Testing in Primary Health Care in Belgrade

This study aimed to (1) analyse the utilization of tests in 15 laboratories associated with primary health care centres in Belgrade between 1985 and 1992 and (2) assess differences and similarities concerning technologies and costs between two comparable laboratories. The number of tests performed at primary health care laboratories in Belgrade has decreased since 1987 with a drastic fall in 1992, corresponding with crisis and war in the country. The comparative analysis of costs between the two laboratories showed significant differences in the way laboratory technicians spent their time and a marked difference in direct and indirect costs between the two laboratories.