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Clinical Chemistry and Laboratory... Mar 2023The EU Diagnostic Device Regulation (IVDR) aims for transparent risk-and purpose-based validation of diagnostic devices, traceability of results to uniquely identified... (Review)
Review
ISO 15189 is a sufficient instrument to guarantee high-quality manufacture of laboratory developed tests for in-house-use conform requirements of the European -Diagnostics Regulation.
The EU Diagnostic Device Regulation (IVDR) aims for transparent risk-and purpose-based validation of diagnostic devices, traceability of results to uniquely identified devices, and post-market surveillance. The IVDR regulates design, manufacture and putting into use of devices, but not medical services using these devices. In the absence of suitable commercial devices, the laboratory can resort to laboratory-developed tests (LDT) for in-house use. Documentary obligations (IVDR Art 5.5), the performance and safety specifications of ANNEX I, and development and manufacture under an ISO 15189-equivalent quality system apply. LDTs serve specific clinical needs, often for low volume niche applications, or correspond to the translational phase of new tests and treatments, often extremely relevant for patient care. As some commercial tests may disappear with the IVDR roll-out, many will require urgent LDT replacement. The workload will also depend on which modifications to commercial tests turns them into an LDT, and on how national legislators and competent authorities (CA) will handle new competences and responsibilities. We discuss appropriate interpretation of ISO 15189 to cover IVDR requirements. Selected cases illustrate LDT implementation covering medical needs with commensurate management of risk emanating from intended use and/or design of devices. Unintended collateral damage of the IVDR comprises loss of non-profitable niche applications, increases of costs and wasted resources, and migration of innovative research to more cost-efficient environments. Taking into account local specifics, the legislative framework should reduce the burden on and associated opportunity costs for the health care system, by making diligent use of existing frameworks.
Topics: Humans; Reagent Kits, Diagnostic; European Union; Clinical Laboratory Services
PubMed: 36716120
DOI: 10.1515/cclm-2023-0045 -
Public Health Action Mar 2020Finding and treating all tuberculosis (TB) patients is crucial for ending TB. We investigated whether rapid diagnostic turnaround time (TAT) and patient tracking could...
Finding and treating all tuberculosis (TB) patients is crucial for ending TB. We investigated whether rapid diagnostic turnaround time (TAT) and patient tracking could increase TB treatment initiation in Maputo, Mozambique. Among 3329 TB patients newly diagnosed by the University Eduardo Mondlane-Anti-Persoonsmijnen Ontmijnende Product Ontwikkeling/Anti-Personnel Landmines Detection Product Development (APOPO) Laboratory between 2013 and 2018, on average 61% were verifiably linked to care. This proportion increased from 54% (first half 2013) to 79% (second half 2018) after introducing a 24-hour TAT in 2015 and patient tracking conducted by a community-based partner, Associação Kenguelekezé, in 2017. Rapid, well-connected TB diagnostic services can reduce pre-treatment loss to follow-up and support the joint initiative of WHO, Stop TB and Global Fund to 'FIND.TREAT.ALL.#EndTB'.
PubMed: 32368516
DOI: 10.5588/pha.19.0037 -
BMJ Open Dec 2021Waiting times in the UK for an autism diagnostic assessment have increased rapidly in the last 5 years. This review explored research (including 'grey' literature) to... (Review)
Review
OBJECTIVES
Waiting times in the UK for an autism diagnostic assessment have increased rapidly in the last 5 years. This review explored research (including 'grey' literature) to uncover the current evidence base about autism diagnostic pathways and what works best, for whom and in what circumstances, to deliver high quality and timely diagnosis.
DESIGN
We performed a Rapid Realist Review consistent with recognised standards for realist syntheses. We collected 129 grey literature and policy/guidelines and 220 articles from seven databases (January 2011-December 2019). We developed programme theories of how, why and in what contexts an intervention worked, based on cross comparison and synthesis of evidence. The focus was on identifying factors that contributed to a clearly defined intervention (the diagnostic pathway), associated with specific outcomes (high quality and timely), within specific parameters (Autism diagnostic services in Paediatric and Child & Adolescent Mental Health services in the UK). Our Expert Stakeholder Group, including representatives from local parent forums, national advocacy groups and clinicians, was integral to the process.
RESULTS
Based on 45 relevant articles, we identified 7 programme theories that were integral to the process of diagnostic service delivery. Four were related to the clinical pathway: initial recognition of possible autism; referral and triaging; diagnostic model; and providing feedback to parents. Three programme theories were pertinent to all stages of the referral and diagnostic process: working in partnership with families; interagency working; and training, service evaluation and development.
CONCLUSIONS
This theory informed review of childhood autism diagnostic pathways identified important aspects that may contribute to efficient, high quality and family-friendly service delivery. The programme theories will be further tested through a national survey of current practice and in-depth longitudinal case studies of exemplar services.
TRIAL REGISTRATION NUMBER
NCT04422483.
Topics: Adolescent; Autistic Disorder; Child; Humans; Parents; Referral and Consultation
PubMed: 34907053
DOI: 10.1136/bmjopen-2021-051241 -
JAMA Network Open Aug 2022Delayed engagement in tuberculosis (TB) services is associated with ongoing transmission and poor clinical outcomes.
IMPORTANCE
Delayed engagement in tuberculosis (TB) services is associated with ongoing transmission and poor clinical outcomes.
OBJECTIVE
To assess whether patients with TB have differential preferences for strategies to improve the public health reach of TB diagnostic services.
DESIGN, SETTING, AND PARTICIPANTS
A cross-sectional study was undertaken in which a discrete choice experiment (DCE) was administered between September 18, 2019, and January 17, 2020, to 401 adults (>18 years of age) with microbiologically confirmed TB in Lusaka, Zambia. The DCE had 7 attributes with 2 to 3 levels per attribute related to TB service enhancements. Latent class analysis was used to identify segments of participants with unique preferences. Multiscenario simulations were used to estimate shares of preferences for different TB service improvement strategies.
MAIN OUTCOMES AND MEASURES
The main outcomes were patient preference archetypes and estimated shares of preferences for different strategies to improve TB diagnostic services. Collected data were analyzed between January 3, 2022, to July 2, 2022.
RESULTS
Among 326 adults with TB (median [IQR] age, 34 [27-42] years; 217 [66.8%] male; 158 [48.8%] HIV positive), 3 groups with distinct preferences for TB service improvements were identified. Group 1 (192 participants [58.9%]) preferred a facility that offered same-day TB test results, shorter wait times, and financial incentives for testing. Group 2 (83 participants [25.4%]) preferred a facility that provided same-day TB results, had greater privacy, and was closer to home. Group 3 (51 participants [15.6%]) had no strong preferences for service improvements and had negative preferences for receiving telephone-based TB test results. Groups 1 and 2 were more likely to report at least a 4-week delay in seeking health care for their current TB episode compared with group 3 (29 [51.3%] in group 1, 95 [35.8%] in group 2, and 10 [19.6%] in group 3; P < .001). Strategies to improve TB diagnostic services most preferred by all participants were same-day TB test results alone (shares of preference, 69.9%) and combined with a small financial testing incentive (shares of preference, 79.3%), shortened wait times (shares of preference, 76.1%), or greater privacy (shares of preference, 75.0%). However, the most preferred service improvement strategies differed substantially by group.
CONCLUSIONS AND RELEVANCE
In this study, patients with TB had heterogenous preferences for TB diagnostic service improvements associated with differential health care-seeking behavior. Tailored strategies that incorporate features most valued by persons with undiagnosed TB, including same-day results, financial incentives, and greater privacy, may optimize reach by overcoming key barriers to timely TB care engagement.
Topics: Adult; Cross-Sectional Studies; Diagnostic Services; Female; Humans; Male; Patient Preference; Tuberculosis; Zambia
PubMed: 36036933
DOI: 10.1001/jamanetworkopen.2022.29091 -
The Journal of Molecular Diagnostics :... Mar 2022Clinical laboratories offering genome sequencing have the opportunity to return pharmacogenomic findings to patients, providing the added benefit of preemptive testing...
Clinical laboratories offering genome sequencing have the opportunity to return pharmacogenomic findings to patients, providing the added benefit of preemptive testing that could help inform medication selection or dosing throughout the lifespan. Implementation of pharmacogenomic reporting must address several challenges, including inherent limitations in short-read genome sequencing methods, gene and variant selection, standardization of genotype and phenotype nomenclature, and choice of guidelines and drugs to report. An automated pipeline, lmPGX, was developed as an end-to-end solution that produces two versions of a pharmacogenomic report, presenting either Clinical Pharmacogenetics Implementation Consortium or US Food and Drug Administration guidelines for 12 genes. The pipeline was validated for performance using reference samples and pharmacogenetic data from the Genetic Testing Reference Materials Coordination Program. To determine performance and limitations, lmPGX was compared with three additional publicly available pharmacogenomic pipelines. The lmPGX pipeline offers clinical laboratories an opportunity for seamless integration of pharmacogenomic results with genome reporting.
Topics: Genetic Testing; Genotype; Humans; Pharmacogenetics; Pharmacogenomic Testing; Phenotype
PubMed: 35041930
DOI: 10.1016/j.jmoldx.2021.12.001 -
JAMA Network Open Nov 2022Cannabis use is prevalent and increasing, and frequent use intensifies the risk of cannabis use disorder (CUD). CUD is underrecognized in medical settings, but a...
IMPORTANCE
Cannabis use is prevalent and increasing, and frequent use intensifies the risk of cannabis use disorder (CUD). CUD is underrecognized in medical settings, but a validated single-item cannabis screen could increase recognition.
OBJECTIVE
To evaluate the Single-Item Screen-Cannabis (SIS-C), administered and documented in routine primary care, compared with a confidential reference standard measure of CUD.
DESIGN, SETTING, AND PARTICIPANTS
This diagnostic study included a sample of adult patients who completed routine cannabis screening between January 28 and September 12, 2019, and were randomly selected for a confidential survey about cannabis use. Random sampling was stratified by frequency of past-year use and race and ethnicity. The study was conducted at an integrated health system in Washington state, where adult cannabis use is legal. Data were analyzed from May 2021 to March 2022.
EXPOSURES
The SIS-C asks about frequency of past-year cannabis use with responses (none, less than monthly, monthly, weekly, daily or almost daily) documented in patients' medical records.
MAIN OUTCOMES AND MEASURES
The Diagnostic and Statistical Manual, Fifth Edition (DSM-5) Composite International Diagnostic Interview-Substance Abuse Module (CIDI-SAM) for past-year CUD was completed on a confidential survey and considered the reference standard. The SIS-C was compared with 2 or more criteria on the CIDI-SAM, consistent with CUD. All analyses were weighted, accounting for survey design and nonresponse, to obtain estimates representative of the health system primary care population.
RESULTS
Of 5000 sampled adult patients, 1688 responded to the cannabis survey (34% response rate). Patients were predominantly middle-aged (weighted mean [SD] age, 50.7 [18.1]), female or women (weighted proportion [SE], 55.9% [4.1]), non-Hispanic (weighted proportion [SE], 96.7% [1.0]), and White (weighted proportion [SE], 74.2% [3.7]). Approximately 6.6% of patients met criteria for past-year CUD. The SIS-C had an area under receiver operating characteristic curve of 0.89 (95% CI, 0.78-0.96) for identifying CUD. A threshold of less than monthly cannabis use balanced sensitivity (0.88) and specificity (0.83) for detecting CUD. In populations with a 6% prevalence of CUD, predictive values of a positive screen ranged from 17% to 34%, while predictive values of a negative screen ranged from 97% to 100%.
CONCLUSIONS AND RELEVANCE
In this diagnostic study, the SIS-C had excellent performance characteristics in routine care as a screen for CUD. While high negative predictive values suggest that the SIS-C accurately identifies patients without CUD, low positive predictive values indicate a need for further diagnostic assessment following positive results when screening for CUD in primary care.
Topics: Adult; Middle Aged; Humans; Female; Marijuana Abuse; Cannabis; Substance-Related Disorders; Diagnostic and Statistical Manual of Mental Disorders; Mass Screening
PubMed: 36318205
DOI: 10.1001/jamanetworkopen.2022.39772 -
PloS One 2022Information on laboratory test availability and current testing scope among general hospitals in Kenya is not readily available. We sought to explore the reporting...
INTRODUCTION
Information on laboratory test availability and current testing scope among general hospitals in Kenya is not readily available. We sought to explore the reporting trends and test availability within clinical laboratories in Kenya over a 24-months period through analysis of the laboratory data reported in the District Health Information System (DHIS2).
METHODS
Monthly hospital laboratory testing data were extracted from the Kenyan DHIS2 between January 2018 and December 2019. We used the national laboratory testing summary tool (MoH 706) to identify the tests of interest among 204 general hospitals in Kenya. A local practitioner panel consisting of individuals with laboratory expertise was used to classify the tests as common and uncommon. We compared the tests on the MoH 706 template with the Essential Diagnostic List (EDL) of the World Health Organisation and further reclassified them into test categories based on the EDL for generalisability of our findings. Evaluation of the number of monthly test types reported in each facility and the largest number of tests ever reported in any of the 24 months were used to assess test availability and testing scope, respectively.
RESULTS
Out of the 204 general hospitals assessed, 179 (179/204) reported at least one of the 80 tests of interest in any of the 24 months. Only 41% (74/179) of the reporting hospitals submitted all their monthly DHIS2 laboratory reports for the entire 24 months. The median testing capacity across the hospitals was 40% with a wide variation in testing scope from one hospital laboratory to another (% IQR: 33.8-51.9). Testing scope was inconsistent within facilities as indicated by often large monthly fluctuations in the total number of recommended and EDL tests reported. Tests of anatomical pathology and cancer were the least reported with 4 counties' hospitals not reporting any cancer or anatomical pathology tests for the entire 24 months.
CONCLUSION
The current reporting of laboratory testing information in DHIS2 is poor. Monitoring access and utilisation of laboratory testing across the country would require significant improvements in consistency and coverage of routine laboratory test reporting in DHIS2. Nonetheless, the available data suggest unequal and intermittent population access to laboratory testing provided by general hospitals in Kenya.
Topics: Diagnostic Services; Health Information Systems; Hospitals, General; Humans; Kenya; Laboratories
PubMed: 35395040
DOI: 10.1371/journal.pone.0266667 -
Autism : the International Journal of... Feb 2021With professional training and regular opportunities to observe children interacting with their peers, preschool teachers are in a good position to notice children's...
With professional training and regular opportunities to observe children interacting with their peers, preschool teachers are in a good position to notice children's autism spectrum disorder symptomatology. Yet even when a preschool teacher suspects that a child may have autism spectrum disorder, fear of false alarm may hold the teacher back from alerting the parents, let alone suggesting them to consider clinical assessment for the child. A valid and convenient screening tool can help preschool teachers make more informed and hence more confident judgment. We set out to develop a screening tool that capitalizes on peer interaction as a naturalistic "stress test" to identify children more likely than their peers to have autism spectrum disorder. A total of 304 3- to 4-year-olds were observed at school with an 84-item preliminary checklist; data-driven item reduction yielded a 13-item Classroom Observation Scale. The Classroom Observation Scale scores correlated significantly with Autism Diagnostic Observation Schedule-2 scores. To validate the scale, another 322 2- to 4-year-olds were screened using the Classroom Observation Scale. The screen-positive children and randomly selected typically developing peers were assessed for autism spectrum disorder 1.5 years later. The Classroom Observation Scale as used by teachers and researchers near preschool onset predicted autism spectrum disorder diagnoses 1.5 years later. This user-friendly 13-item Classroom Observation Scale enables teachers and healthcare workers with little or no clinical training to identify, with reliable and valid results, preschoolers more likely than their peers to have autism spectrum disorder.
Topics: Autism Spectrum Disorder; Autistic Disorder; Child, Preschool; Humans; Mass Screening; Parents; School Teachers
PubMed: 33153314
DOI: 10.1177/1362361320967529 -
Genome Medicine Sep 2023Many families and individuals do not meet criteria for a known hereditary cancer syndrome but display unusual clusters of cancers. These families may carry pathogenic...
BACKGROUND
Many families and individuals do not meet criteria for a known hereditary cancer syndrome but display unusual clusters of cancers. These families may carry pathogenic variants in cancer predisposition genes and be at higher risk for developing cancer.
METHODS
This multi-centre prospective study recruited 195 cancer-affected participants suspected to have a hereditary cancer syndrome for whom previous clinical targeted genetic testing was either not informative or not available. To identify pathogenic disease-causing variants explaining participant presentation, germline whole-genome sequencing (WGS) and a comprehensive cancer virtual gene panel analysis were undertaken.
RESULTS
Pathogenic variants consistent with the presenting cancer(s) were identified in 5.1% (10/195) of participants and pathogenic variants considered secondary findings with potential risk management implications were identified in another 9.7% (19/195) of participants. Health economic analysis estimated the marginal cost per case with an actionable variant was significantly lower for upfront WGS with virtual panel ($8744AUD) compared to standard testing followed by WGS ($24,894AUD). Financial analysis suggests that national adoption of diagnostic WGS testing would require a ninefold increase in government annual expenditure compared to conventional testing.
CONCLUSIONS
These findings make a case for replacing conventional testing with WGS to deliver clinically important benefits for cancer patients and families. The uptake of such an approach will depend on the perspectives of different payers on affordability.
Topics: Humans; Prospective Studies; Neoplastic Syndromes, Hereditary; Oncogenes; Genetic Testing; Germ Cells
PubMed: 37723522
DOI: 10.1186/s13073-023-01223-1 -
Genes Feb 2022Next-generation sequencing (NGS) has revealed large numbers of genetic variants in LGMD-related genes, with most of them classified as variants of uncertain significance... (Review)
Review
Next-generation sequencing (NGS) has revealed large numbers of genetic variants in LGMD-related genes, with most of them classified as variants of uncertain significance (VUSs). VUSs are genetic changes with unknown pathological impact and present a major challenge in genetic test interpretation and disease diagnosis. Understanding the phenotypic consequences of VUSs can provide clinical guidance regarding LGMD risk and therapy. In this review, we provide a brief overview of the subtypes of LGMD, disease diagnosis, current classification systems for investigating VUSs, and a potential deep mutational scanning approach to classify VUSs in LGMD-related genes.
Topics: Genetic Testing; High-Throughput Nucleotide Sequencing; Mutation
PubMed: 35205425
DOI: 10.3390/genes13020382