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1.
Malar J ; 23(1): 120, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38664678

ABSTRACT

BACKGROUND: The increased availability and use of malaria rapid diagnostic test (RDT) by primary healthcare (PHC) workers has made universal diagnostic testing before malaria treatment more feasible. However, to meaningfully resolve the problem of over-treatment with artemisinin-based combination therapy and the heightened risk of selection pressure and drug resistance, there should be appropriate response (non-prescription of anti-malarial drugs) following a negative RDT result by PHC workers. This study explored the determinants of the use of RDT and anti-malarial drug prescription practices by PHC workers in Ebonyi state, Nigeria. METHODS: Between March 2 and 10, 2020, three focus group discussions were conducted in English with 23 purposively-selected consenting PHC workers involved in the diagnosis and treatment of malaria. Data was analysed thematically as informed by the method by Braun and Clarke. RESULTS: The determinants of the use of RDT for malaria diagnosis were systemic (RDT availability and patient load), provider related (confidence in RDT and the desire to make correct diagnosis, PHC worker's knowledge and training, and fear to prick a patient), client related (fear of needle prick and refusal to receive RDT, and self-diagnosis of malaria, based on symptoms, and insistence on not receiving RDT), and RDT-related (the ease of conducting and interpreting RDT). The determinants of anti-malarial drug prescription practices were systemic (drug availability and cost) and drug related (effectiveness and side-effects of the drugs). The determinants of the prescription of anti-malarial drugs following negative RDT were provider related (the desire to make more money and limited confidence in RDT) and clients' demand while unnecessary co-prescription of antibiotics with anti-malarial drugs following positive RDT was determined by the desire to make more money. CONCLUSIONS: This evidence highlights many systemic, provider, client, and RDT/drug related determinants of PHC workers' use of RDT and anti-malarial drug prescription practices that should provide tailored guidance for relevant health policy actions in Ebonyi state, Nigeria, and similar settings.


Subject(s)
Antimalarials , Diagnostic Tests, Routine , Health Personnel , Malaria , Primary Health Care , Nigeria , Antimalarials/therapeutic use , Diagnostic Tests, Routine/statistics & numerical data , Malaria/drug therapy , Malaria/diagnosis , Humans , Health Personnel/statistics & numerical data , Male , Female , Adult , Middle Aged , Drug Prescriptions/statistics & numerical data , Focus Groups , Qualitative Research , Rapid Diagnostic Tests
2.
PLoS Negl Trop Dis ; 18(4): e0012077, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38598549

ABSTRACT

BACKGROUND: Fever is the most frequent symptom in patients seeking care in South and Southeast Asia. The introduction of rapid diagnostic tests (RDTs) for malaria continues to drive patient management and care. Malaria-negative cases are commonly treated with antibiotics without confirmation of bacteraemia. Conventional laboratory tests for differential diagnosis require skilled staff and appropriate access to healthcare facilities. In addition, introducing single-disease RDTs instead of conventional laboratory tests remains costly. To overcome some of the delivery challenges of multiple separate tests, a multiplexed RDT with the capacity to diagnose a diverse range of tropical fevers would be a cost-effective solution. In this study, a multiplex lateral flow immunoassay (DPP Fever Panel II Assay) that can detect serum immunoglobulin M (IgM) and specific microbial antigens of common fever agents in Asia (Orientia tsutsugamushi, Rickettsia typhi, Leptospira spp., Burkholderia pseudomallei, Dengue virus, Chikungunya virus, and Zika virus), was evaluated. METHODOLOGY/PRINCIPAL FINDINGS: Whole blood (WB) and serum samples from 300 patients with undefined febrile illness (UFI) recruited in Vientiane, Laos PDR were tested using the DPP Fever Panel II, which consists of an Antibody panel and Antigen panel. To compare reader performance, results were recorded using two DPP readers, DPP Micro Reader (Micro Reader 1) and DPP Micro Reader Next Generation (Micro Reader 2). WB and serum samples were run on the same fever panel and read on both micro readers in order to compare results. ROC analysis and equal variance analysis were performed to inform the diagnostic validity of the test compared against the respective reference standards of each fever agent (S1 Table). Overall better AUC values were observed in whole blood results. No significant difference in AUC performance was observed when comparing whole blood and serum sample testing, except for when testing for R. typhi IgM (p = 0.04), Leptospira IgM (p = 0.02), and Dengue IgG (p = 0.03). Linear regression depicted R2 values had ~70% agreement across WB and serum samples, except when testing for leptospirosis and Zika, where the R2 values were 0.37 and 0.47, respectively. No significant difference was observed between the performance of Micro Reader 1 and Micro Reader 2, except when testing for the following pathogens: Zika IgM, Zika IgG, and B pseudomallei CPS Ag. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that the diagnostic accuracy of the DPP Fever Panel II is comparable to that of commonly used RDTs. The optimal cut-off would depend on the use of the test and the desired sensitivity and specificity. Further studies are required to authenticate the use of these cut-offs in other endemic regions. This multiplex RDT offers diagnostic benefits in areas with limited access to healthcare and has the potential to improve field testing capacities. This could improve tropical fever management and reduce the public health burden in endemic low-resource areas.


Subject(s)
Immunoglobulin M , Sensitivity and Specificity , Humans , Immunoglobulin M/blood , Female , Male , Laos , Adult , Fever/diagnosis , Antibodies, Bacterial/blood , Diagnostic Tests, Routine/methods , Middle Aged , Adolescent , Young Adult , Antibodies, Viral/blood , Antigens, Bacterial/immunology , Antigens, Bacterial/analysis , Immunoassay/methods , Immunoassay/standards
3.
Biom J ; 66(3): e2300175, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38637326

ABSTRACT

In screening large populations a diagnostic test is frequently used repeatedly. An example is screening for bowel cancer using the fecal occult blood test (FOBT) on several occasions such as at 3 or 6 days. The question that is addressed here is how often should we repeat a diagnostic test when screening for a specific medical condition. Sensitivity is often used as a performance measure of a diagnostic test and is considered here for the individual application of the diagnostic test as well as for the overall screening procedure. The latter can involve an increasingly large number of repeated applications, but how many are sufficient? We demonstrate the issues involved in answering this question using real data on bowel cancer at St Vincents Hospital in Sydney. As data are only available for those testing positive at least once, an appropriate modeling technique is developed on the basis of the zero-truncated binomial distribution which allows for population heterogeneity. The latter is modeled using discrete nonparametric maximum likelihood. If we wish to achieve an overall sensitivity of 90%, the FOBT should be repeated for 2 weeks instead of the 1 week that was used at the time of the survey. A simulation study also shows consistency in the sense that bias and standard deviation for the estimated sensitivity decrease with an increasing number of repeated occasions as well as with increasing sample size.


Subject(s)
Colorectal Neoplasms , Humans , Colorectal Neoplasms/diagnosis , Occult Blood , Sample Size , Diagnostic Tests, Routine , Mass Screening/methods
4.
BMC Infect Dis ; 24(1): 404, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38622499

ABSTRACT

Severe malaria is not routinely considered when evaluating a febrile patient in the postoperative setting. Common bacterial infections, along with adverse drug reactions, are the usual differential concerns. We present a case of severe malaria emerging unexpectedly eight days after routine craniotomy.


Subject(s)
Malaria , Humans , New York , Malaria/diagnosis , Malaria/drug therapy , Fever/microbiology , Patients , Diagnostic Tests, Routine
5.
Malar J ; 23(1): 108, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38632640

ABSTRACT

BACKGROUND: Rapid diagnostic tests (RDTs) play a significant role in expanding case management in peripheral healthcare systems. Histidine-rich protein-2 (HRP2) antigen detection RDTs are predominantly used to diagnose Plasmodium falciparum infection. However, the evolution and spread of P. falciparum parasite strains with deleted hrp2/3 genes, causing false-negative results, have been reported. This study assessed the diagnostic performance of HRP2-detecting RDTs for P. falciparum cases and the prevalence of pfhrp2/3 deletions among symptomatic patients seeking malaria diagnosis at selected health facilities in southern Ethiopia. METHODS: A multi-health facilities-based cross-sectional study was conducted on self-presenting febrile patients seeking treatment in southern Ethiopia from July to September 2022. A purposive sampling strategy was used to enroll patients with microscopically confirmed P. falciparum infections. A capillary blood sample was obtained to prepare a blood film for microscopy and a RDT using the SD Bioline™ Malaria Pf/Pv Test. Dried blood spot samples were collected for further molecular analysis. DNA was extracted using gene aid kits and amplification was performed using nested PCR assay. Exon 2 of hrp2 and hrp3, which are the main protein-coding regions, was used to confirm its deletion. The diagnostic performance of RDT was evaluated using PCR as the gold standard test for P. falciparum infections. RESULTS: Of 279 P. falciparum PCR-confirmed samples, 249 (89.2%) had successful msp-2 amplification, which was then genotyped for hrp2/3 gene deletions. The study revealed that pfhrp2/3 deletions were common in all health centres, and it was estimated that 144 patients (57.8%) across all health facilities had pfhrp2/3 deletions, leading to false-negative PfHRP2 RDT results. Deletions spanning exon 2 of hrp2, exon 2 of hrp3, and double deletions (hrp2/3) accounted for 68 (27.3%), 76 (30.5%), and 33 (13.2%) of cases, respectively. The study findings revealed the prevalence of P. falciparum parasites lacking a single pfhrp2-/3-gene and that both genes varied across the study sites. This study also showed that the sensitivity of the SD Bioline PfHRP2-RDT test was 76.5% when PCR was used as the reference test. CONCLUSION: This study confirmed the existence of widespread pfhrp2/3- gene deletions, and their magnitude exceeded the WHO-recommended threshold (> 5%). False-negative RDT results resulting from deletions in Pfhrp2/3- affect a country's attempts at malaria control and elimination. Therefore, the adoption of non-HRP2-based RDTs as an alternative measure is required to avoid the consequences associated with the continued use of HRP-2-based RDTs, in the study area in particular and in Ethiopia in general.


Subject(s)
Malaria, Falciparum , Protozoan Proteins , Humans , Protozoan Proteins/genetics , Antigens, Protozoan/genetics , Plasmodium falciparum/genetics , Histidine/genetics , Cross-Sectional Studies , Ethiopia , Diagnostic Tests, Routine/methods , Malaria, Falciparum/epidemiology , Gene Deletion
7.
Sci Rep ; 14(1): 8158, 2024 04 08.
Article in English | MEDLINE | ID: mdl-38589477

ABSTRACT

Plasmodium falciparum with the histidine rich protein 2 gene (pfhrp2) deleted from its genome can escape diagnosis by HRP2-based rapid diagnostic tests (HRP2-RDTs). The World Health Organization (WHO) recommends switching to a non-HRP2 RDT for P. falciparum clinical case diagnosis when pfhrp2 deletion prevalence causes ≥ 5% of RDTs to return false negative results. Tanzania is a country of heterogenous P. falciparum transmission, with some regions approaching elimination and others at varying levels of control. In concordance with the current recommended WHO pfhrp2 deletion surveillance strategy, 100 health facilities encompassing 10 regions of Tanzania enrolled malaria-suspected patients between February and July 2021. Of 7863 persons of all ages enrolled and providing RDT result and blood sample, 3777 (48.0%) were positive by the national RDT testing for Plasmodium lactate dehydrogenase (pLDH) and/or HRP2. A second RDT testing specifically for the P. falciparum LDH (Pf-pLDH) antigen found 95 persons (2.5% of all RDT positives) were positive, though negative by the national RDT for HRP2, and were selected for pfhrp2 and pfhrp3 (pfhrp2/3) genotyping. Multiplex antigen detection by laboratory bead assay found 135/7847 (1.7%) of all blood samples positive for Plasmodium antigens but very low or no HRP2, and these were selected for genotyping as well. Of the samples selected for genotyping based on RDT or laboratory multiplex result, 158 were P. falciparum DNA positive, and 140 had sufficient DNA to be genotyped for pfhrp2/3. Most of these (125/140) were found to be pfhrp2+/pfhrp3+, with smaller numbers deleted for only pfhrp2 (n = 9) or only pfhrp3 (n = 6). No dual pfhrp2/3 deleted parasites were observed. This survey found that parasites with these gene deletions are rare in Tanzania, and estimated that 0.24% (95% confidence interval: 0.08% to 0.39%) of false-negative HRP2-RDTs for symptomatic persons were due to pfhrp2 deletions in this 2021 Tanzania survey. These data provide evidence for HRP2-based diagnostics as currently accurate for P. falciparum diagnosis in Tanzania.


Subject(s)
Blood Group Antigens , Malaria, Falciparum , Humans , Plasmodium falciparum/genetics , Protozoan Proteins/genetics , Gene Deletion , Tanzania/epidemiology , Diagnostic Tests, Routine/methods , Antigens, Protozoan/genetics , Malaria, Falciparum/diagnosis , Malaria, Falciparum/epidemiology , Malaria, Falciparum/genetics , Health Facilities , DNA
8.
World J Gastroenterol ; 30(6): 579-598, 2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38463019

ABSTRACT

BACKGROUND: Helicobacter pylori (H. pylori) infection has been well-established as a significant risk factor for several gastrointestinal disorders. The urea breath test (UBT) has emerged as a leading non-invasive method for detecting H. pylori. Despite numerous studies confirming its substantial accuracy, the reliability of UBT results is often compromised by inherent limitations. These findings underscore the need for a rigorous statistical synthesis to clarify and reconcile the diagnostic accuracy of the UBT for the diagnosis of H. pylori infection. AIM: To determine and compare the diagnostic accuracy of 13C-UBT and 14C-UBT for H. pylori infection in adult patients with dyspepsia. METHODS: We conducted an independent search of the PubMed/MEDLINE, EMBASE, and Cochrane Central databases until April 2022. Our search included diagnostic accuracy studies that evaluated at least one of the index tests (13C-UBT or 14C-UBT) against a reference standard. We used the QUADAS-2 tool to assess the methodological quality of the studies. We utilized the bivariate random-effects model to calculate sensitivity, specificity, positive and negative test likelihood ratios (LR+ and LR-), as well as the diagnostic odds ratio (DOR), and their 95% confidence intervals. We conducted subgroup analyses based on urea dosing, time after urea administration, and assessment technique. To investigate a possible threshold effect, we conducted Spearman correlation analysis, and we generated summary receiver operating characteristic (SROC) curves to assess heterogeneity. Finally, we visually inspected a funnel plot and used Egger's test to evaluate publication bias. RESULTS: The titles and abstracts of 4621 studies were screened; 79 articles were retrieved and selected for full-text reading. Finally, 60 studies were included in the diagnostic test accuracy meta-analysis. Our analysis demonstrates superior diagnostic accuracy of 13C-UBT over 14C-UBT, indicated by higher sensitivity (96.60% vs 96.15%), specificity (96.93% vs 89.84%), likelihood ratios (LR+ 22.00 vs 10.10; LR- 0.05 vs 0.06), and area under the curve (AUC; 0.979 vs 0.968). Notably, 13C-UBT's DOR (586.47) significantly outperforms 14C-UBT (DOR 226.50), making it the preferred diagnostic tool for dyspeptic individuals with H. pylori infection. Correlation analysis revealed no threshold effect (13C-UBT: r = 0.48; 14C-UBT: r = -0.01), and SROC curves showed consistent accuracy. Both 13C-UBT and 14C-UBT showed high AUC values (13C-UBT 0.979; 14C-UBT 0.968) near 1.00, reinforcing their excellent accuracy and endorsing both as reliable diagnostic tools in clinical practice. CONCLUSION: In summary, our study has demonstrated that 13C-UBT has been found to outperform the 14C-UBT, making it the preferred diagnostic approach. Additionally, our results emphasize the significance of carefully considering urea dosage, assessment timing, and measurement techniques for both tests to enhance diagnostic precision. Nevertheless, it is crucial for researchers and clinicians to evaluate the strengths and limitations of our findings before implementing them in practice.


Subject(s)
Helicobacter Infections , Helicobacter pylori , Adult , Humans , Helicobacter Infections/diagnosis , Urea , Reproducibility of Results , Sensitivity and Specificity , Breath Tests/methods , Diagnostic Tests, Routine
9.
Lancet Microbe ; 5(4): e366-e378, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38467130

ABSTRACT

BACKGROUND: Accurate diagnosis is pivotal for implementing strategies for surveillance, control, and elimination of schistosomiasis. Despite their low sensitivity in low-endemicity areas, microscopy-based urine filtration and the Kato-Katz technique are considered as reference diagnostic tests for Schistosoma haematobium and Schistosoma mansoni infections, respectively. We aimed to collate all available evidence on the accuracy of other proposed diagnostic techniques. METHODS: In this systematic review and meta-analysis, we searched PubMed, Embase, the Cochrane Library, and LILACS for studies published from database inception to Dec 31, 2022, investigating the sensitivity and specificity of diagnostic tests for S haematobium and S mansoni infections against Kato-Katz thick smears or urine microscopy (reference tests) involving adults (aged ≥18 years), school-aged children (aged 7 to 18 years), or preschool-aged children (aged 1 month to 7 years). We extracted raw data on true positives, true negatives, false positives, and false negatives for the diagnostic tests and data on the number of participants, study authors, publication year, journal, study design, participants' age and sex, prevalence of Schistosoma infection, and treatment status. To account for imperfect reference tests, we used a hierarchical Bayesian latent class meta-analysis to model test accuracy. FINDINGS: Overall, we included 121 studies, assessing 28 different diagnostic techniques. Most studies (103 [85%] of 121) were done in Africa, 14 (12%) in South America, one (1%) in Asia, and one (1%) in an unknown country. Compared with the reference test, Kato-Katz thick smears, circulating cathodic antigen urine cassette assay version 1 (CCA1, 36 test comparisons) had excellent sensitivity (95% [95% credible interval 88-99]) and reasonable specificity (74% [63-83]) for S mansoni. ELISA-based tests had a performance comparable to circulating cathodic antigen, but there were few available test comparisons. For S haematobium, proteinuria (42 test comparisons, sensitivity 73% [62-82]; specificity 94% [89-98]) and haematuria (75 test comparisons, sensitivity 85% [80-90]; specificity 96% [92-99]) reagent strips showed high specificity, with haematuria reagent strips having better sensitivity. Despite limited data, nucleic acid amplification tests (NAATs; eg, PCR or loop-mediated isothermal amplification [LAMP]) showed promising results with sensitivity estimates above 90%. We found an unclear risk of bias of about 70% in the use of the reference or index tests and of 50% in patient selection. All analyses showed substantial heterogeneity (I2>80%). INTERPRETATION: Although NAATs and immunological diagnostics show promise, the limited information available precludes drawing definitive conclusions. Additional research on diagnostic accuracy and cost-effectiveness is needed before the replacement of conventional tests can be considered. FUNDING: WHO and Luxembourg Institute of Health.


Subject(s)
Schistosoma mansoni , Schistosomiasis haematobia , Child , Child, Preschool , Adult , Animals , Humans , Adolescent , Schistosoma haematobium , Hematuria/diagnosis , Reagent Strips , Microscopy , Bayes Theorem , Feces , Antigens, Helminth/urine , Urinalysis , Schistosomiasis haematobia/diagnosis , Diagnostic Tests, Routine/methods
10.
Lancet Child Adolesc Health ; 8(5): 358-368, 2024 May.
Article in English | MEDLINE | ID: mdl-38499017

ABSTRACT

BACKGROUND: Febrile infants presenting in the first 90 days of life are at higher risk of invasive and serious bacterial infections than older children. Modern clinical practice guidelines, mostly using procalcitonin as a diagnostic biomarker, can identify infants who are at low risk and therefore suitable for tailored management. C-reactive protein, by comparison, is widely available, but whether C-reactive protein and procalcitonin have similar diagnostic accuracy is unclear. We aimed to compare the test accuracy of procalcitonin and C-reactive protein in the prediction of invasive or serious bacterial infections in febrile infants. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, Web of Science, and The Cochrane Library for diagnostic test accuracy studies up to June 19, 2023, using MeSH terms "procalcitonin", and "bacterial infection" or "fever" and keywords "invasive bacterial infection*" and "serious bacterial infection*", without language or date restrictions. Studies were selected by independent authors against eligibility criteria. Eligible studies included participants aged 90 days or younger presenting to hospital with a fever (≥38°C) or history of fever within the preceding 48 h. The primary index test was procalcitonin, and the secondary index test was C-reactive protein. Test kits had to be commercially available, and test samples had to be collected upon presentation to hospital. Invasive bacterial infection was defined as the presence of a bacterial pathogen in blood or cerebrospinal fluid, as detected by culture or quantitative PCR; authors' definitions of serious bacterial infection were used. Data were extracted from selected studies, and the detection of invasive or serious bacterial infections was analysed with two models for each biomarker. Diagnostic accuracy was determined against internationally recognised cutoff values (0·5 ng/mL for procalcitonin, 20 mg/L for C-reactive protein) and pooled to calculate partial area under the curve (pAUC) values for each biomarker. Optimum cutoff values were identified for each biomarker. This study is registered with PROSPERO, CRD42022293284. FINDINGS: Of 734 studies derived from the literature search, 14 studies (n=7755) were included in the meta-analysis. For the detection of invasive bacterial infections, pAUC values were greater for procalcitonin (0·72, 95% CI 0·56-0·79) than C-reactive protein (0·28, 0·17-0·61; p=0·016). Optimal cutoffs for detecting invasive bacterial infections were 0·49 ng/mL for procalcitonin and 13·12 mg/L for C-reactive protein. For the detection of serious bacterial infections, procalcitonin and C-reactive protein had similar pAUC values (0·55, 0·44-0·69 vs 0·54, 0·40-0·61; p=0·92). For serious bacterial infections, the optimal cutoffs for procalcitonin and C-reactive protein were 0·17 ng/mL and 16·18 mg/L, respectively. Heterogeneity was low for studies investigating the test accuracy of procalcitonin in detecting invasive bacterial infection (I2=23·5%), high for studies investigating procalcitonin for serious bacterial infection (I2=75·5%), and moderate for studies investigating C-reactive protein for invasive bacterial infection (I2=49·5%) and serious bacterial infection (I2=28·3%). The absence of a single definition of serious bacterial infection across studies was the greatest source of interstudy variability and potential bias. INTERPRETATION: Within a large cohort of febrile infants, a procalcitonin cutoff of 0·5 ng/mL had a superior pAUC value to a C-reactive protein cutoff of 20 mg/L for identifying invasive bacterial infections. In settings without access to procalcitonin, C-reactive protein should therefore be used cautiously for the identification of invasive bacterial infections, and a cutoff value below 20 mg/L should be considered. C-reactive protein and procalcitonin showed similar test accuracy for the identification of serious bacterial infection with internationally recognised cutoff values. This might reflect the challenges involved in confirming serious bacterial infection and the absence of a universally accepted definition of serious bacterial infection. FUNDING: None.


Subject(s)
Bacterial Infections , C-Reactive Protein , Infant , Child , Humans , Adolescent , C-Reactive Protein/analysis , Procalcitonin , Fever/diagnosis , Biomarkers , Bacterial Infections/diagnosis , Diagnostic Tests, Routine
11.
Stat Methods Med Res ; 33(5): 875-893, 2024 May.
Article in English | MEDLINE | ID: mdl-38502023

ABSTRACT

The empirical likelihood is a powerful nonparametric tool, that emulates its parametric counterpart-the parametric likelihood-preserving many of its large-sample properties. This article tackles the problem of assessing the discriminatory power of three-class diagnostic tests from an empirical likelihood perspective. In particular, we concentrate on interval estimation in a three-class receiver operating characteristic analysis, where a variety of inferential tasks could be of interest. We present novel theoretical results and tailored techniques studied to efficiently solve some of such tasks. Extensive simulation experiments are provided in a supporting role, with our novel proposals compared to existing competitors, when possible. It emerges that our new proposals are extremely flexible, being able to compete with contestants and appearing suited to accommodating several distributions, such, for example, mixtures, for target populations. We illustrate the application of the novel proposals with a real data example. The article ends with a discussion and a presentation of some directions for future research.


Subject(s)
ROC Curve , Likelihood Functions , Humans , Diagnostic Tests, Routine/statistics & numerical data , Models, Statistical , Computer Simulation
12.
PLoS One ; 19(3): e0295049, 2024.
Article in English | MEDLINE | ID: mdl-38530827

ABSTRACT

Malaria rapid diagnostic tests (mRDTs) are an essential diagnostic tool in low-resource settings; however, administration and interpretation errors reduce their effectiveness. HealthPulse, a smartphone mRDT reader application, was developed by Audere to aid health workers in mRDT administration and interpretation, with an aim to improve the mRDT testing process and facilitate timely decision making through access to digitized results. Audere partnered with PSI and PS Kenya to conduct a pilot study in Busia County, Kenya between March and September 2021 to assess the feasibility and acceptability of HealthPulse to support malaria parasitological diagnosis by community health volunteers (CHVs) and private clinic health workers (private clinic HWs). Metadata was interpreted to assess adherence to correct use protocols and health worker perceptions of the app. Changes to mRDT implementation knowledge were measured through baseline and endline surveys. The baseline survey identified clear mRDT implementation gaps, such as few health workers correctly knowing the number of diluent drops and minimum and maximum wait times for mRDT interpretation, although health worker knowledge improved after using the app. Endline survey results showed that 99.6% of health workers found the app useful and 90.1% found the app easy to use. Process control data showed that most mRDTs (89.2%) were photographed within the recommended 30-minute time frame and that 91.4% of uploaded photos passed the app filter quality check on the first submission. During 154 encounters (3.5% of all encounters) a health worker dispensed an artemisinin-based combination therapy (ACT) to their patient even with a negative mRDT readout. Overall, study results indicated that HealthPulse holds potential as a mobile tool for use in low-resource settings, with future supportive supervision, diagnostic, and surveillance benefits. Follow-up studies will aim to more deeply understand the utility and acceptance of the HealthPulse app.


Subject(s)
Antimalarials , Malaria , Mobile Applications , Humans , Kenya , Feasibility Studies , Pilot Projects , Malaria/diagnosis , Diagnostic Tests, Routine/methods , Antimalarials/therapeutic use
13.
PLoS Negl Trop Dis ; 18(3): e0012054, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38484012

ABSTRACT

BACKGROUND: The parasitic disease loiasis is associated with significant morbidity and mortality. Individuals with hyper-microfilaremia (greater than 20,000 microfilariae per mL of blood) may suffer from serious treatment-related or spontaneous adverse events. Diagnosing loiasis remains complex and primarily relies on direct parasite detection. In this study, we analyzed the performance of various diagnostic tests and the influence of parasitological and clinical factors on test outcomes in samples from individuals living in an endemic region. METHODS: Data and samples were collected from rural Gabon. Loiasis was defined as either detectable microfilaremia, or a positive history of eyeworm as assessed by the RAPLOA questionnaire. Diagnostic testing included a quantitative PCR (qPCR) for detection of Loa loa DNA in blood samples, an in-house crude L. loa antigen IgG ELISA, and a rapid test for antibodies against the Ll-SXP-1 antigen (RDT). Sensitivity and specificity were determined for each test and factors potentially influencing outcomes were evaluated in an exploratory analysis. RESULTS: ELISA, RDT and qPCR results were available for 99.8%, 78.5%, and 100% of the 1,232 participants, respectively. The ELISA and RDT had only modest diagnostic accuracy. qPCR was specific for L. loa microfilaremia and Cycle threshold values correlated with microfilarial density. Anti-L. loa IgG levels were highest in occult loiasis, and antibody levels correlated inversely with L. loa microfilarial density as did RDT line intensities. Only 84.6% and 16.7% of hyper-microfilaremic individuals tested positive by ELISA (11/13) and RDT (2/12), respectively. CONCLUSION: None of the tests demonstrated high sensitivity and specificity for loiasis. Indirect diagnostic assays were characterized by low specificity. Additionally, hyper-microfilaremic individuals often tested negative by RDT and ELISA, indicating that these tests are not suitable for individual case management in endemic populations.


Subject(s)
Loiasis , Animals , Humans , Loiasis/parasitology , Loa/genetics , Microfilariae , Serologic Tests , Antibodies, Helminth , Immunoglobulin G , Diagnostic Tests, Routine
14.
Stat Methods Med Res ; 33(4): 669-680, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38490184

ABSTRACT

Diagnostic accuracy studies assess the sensitivity and specificity of a new index test in relation to an established comparator or the reference standard. The development and selection of the index test are usually assumed to be conducted prior to the accuracy study. In practice, this is often violated, for instance, if the choice of the (apparently) best biomarker, model or cutpoint is based on the same data that is used later for validation purposes. In this work, we investigate several multiple comparison procedures which provide family-wise error rate control for the emerging multiple testing problem. Due to the nature of the co-primary hypothesis problem, conventional approaches for multiplicity adjustment are too conservative for the specific problem and thus need to be adapted. In an extensive simulation study, five multiple comparison procedures are compared with regard to statistical error rates in least-favourable and realistic scenarios. This covers parametric and non-parametric methods and one Bayesian approach. All methods have been implemented in the new open-source R package cases which allows us to reproduce all simulation results. Based on our numerical results, we conclude that the parametric approaches (maxT and Bonferroni) are easy to apply but can have inflated type I error rates for small sample sizes. The two investigated Bootstrap procedures, in particular the so-called pairs Bootstrap, allow for a family-wise error rate control in finite samples and in addition have a competitive statistical power.


Subject(s)
Diagnostic Tests, Routine , Bayes Theorem , Data Interpretation, Statistical , Computer Simulation , Sample Size
15.
Clin Oral Investig ; 28(3): 186, 2024 Mar 02.
Article in English | MEDLINE | ID: mdl-38430334

ABSTRACT

OBJECTIVES: Temporomandibular disorders (TMDs) are the second most common musculoskeletal condition which are challenging tasks for most clinicians. Recent research used machine learning (ML) algorithms to diagnose TMDs intelligently. This study aimed to systematically evaluate the quality of these studies and assess the diagnostic accuracy of existing models. MATERIALS AND METHODS: Twelve databases (Europe PMC, Embase, etc.) and two registers were searched for published and unpublished studies using ML algorithms on medical images. Two reviewers extracted the characteristics of studies and assessed the methodological quality using the QUADAS-2 tool independently. RESULTS: A total of 28 studies (29 reports) were included: one was at unclear risk of bias and the others were at high risk. Thus the certainty of evidence was quite low. These studies used many types of algorithms including 8 machine learning models (logistic regression, support vector machine, random forest, etc.) and 15 deep learning models (Resnet152, Yolo v5, Inception V3, etc.). The diagnostic accuracy of a few models was relatively satisfactory. The pooled sensitivity and specificity were 0.745 (0.660-0.814) and 0.770 (0.700-0.828) in random forest, 0.765 (0.686-0.829) and 0.766 (0.688-0.830) in XGBoost, and 0.781 (0.704-0.843) and 0.781 (0.704-0.843) in LightGBM. CONCLUSIONS: Most studies had high risks of bias in Patient Selection and Index Test. Some algorithms are relatively satisfactory and might be promising in intelligent diagnosis. Overall, more high-quality studies and more types of algorithms should be conducted in the future. CLINICAL RELEVANCE: We evaluated the diagnostic accuracy of the existing models and provided clinicians with much advice about the selection of algorithms. This study stated the promising orientation of future research, and we believe it will promote the intelligent diagnosis of TMDs.


Subject(s)
Diagnostic Imaging , Machine Learning , Temporomandibular Joint Disorders , Humans , Diagnostic Tests, Routine , Radiography , Sensitivity and Specificity , Temporomandibular Joint Disorders/diagnostic imaging
16.
JAMA Netw Open ; 7(2): e240649, 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38421646

ABSTRACT

Importance: Systematic reviews of medical imaging diagnostic test accuracy (DTA) studies are affected by between-study heterogeneity due to a range of factors. Failure to appropriately assess the extent and causes of heterogeneity compromises the interpretability of systematic review findings. Objective: To assess how heterogeneity has been examined in medical imaging DTA studies. Evidence Review: The PubMed database was searched for systematic reviews of medical imaging DTA studies that performed a meta-analysis. The search was limited to the 40 journals with highest impact factor in the radiology, nuclear medicine, and medical imaging category in the InCites Journal Citation Reports of 2021 to reach a sample size of 200 to 300 included studies. Descriptive analysis was performed to characterize the imaging modality, target condition, type of meta-analysis model used, strategies for evaluating heterogeneity, and sources of heterogeneity identified. Multivariable logistic regression was performed to assess whether any factors were associated with at least 1 source of heterogeneity being identified in the included meta-analyses. Methodological quality evaluation was not performed. Data analysis occurred from October to December 2022. Findings: A total of 242 meta-analyses involving a median (range) of 987 (119-441 510) patients across a diverse range of disease categories and imaging modalities were included. The extent of heterogeneity was adequately described (ie, whether it was absent, low, moderate, or high) in 220 studies (91%) and was most commonly assessed using the I2 statistic (185 studies [76%]) and forest plots (181 studies [75%]). Heterogeneity was rated as moderate to high in 191 studies (79%). Of all included meta-analyses, 122 (50%) performed subgroup analysis and 87 (36%) performed meta-regression. Of the 242 studies assessed, 189 (78%) included 10 or more primary studies. Of these 189 studies, 60 (32%) did not perform meta-regression or subgroup analysis. Reasons for being unable to investigate sources of heterogeneity included inadequate reporting of primary study characteristics and a low number of included primary studies. Use of meta-regression was associated with identification of at least 1 source of variability (odds ratio, 1.90; 95% CI, 1.11-3.23; P = .02). Conclusions and Relevance: In this systematic review of assessment of heterogeneity in medical imaging DTA meta-analyses, most meta-analyses were impacted by a moderate to high level of heterogeneity, presenting interpretive challenges. These findings suggest that, despite the development and availability of more rigorous statistical models, heterogeneity appeared to be incomplete, inconsistently evaluated, or methodologically questionable in many cases, which lessened the interpretability of the analyses performed; comprehensive heterogeneity assessment should be addressed at the author level by improving personal familiarity with appropriate statistical methodology for assessing heterogeneity and involving biostatisticians and epidemiologists in study design, as well as at the editorial level, by mandating adherence to methodologic standards in primary DTA studies and DTA meta-analyses.


Subject(s)
Data Analysis , Diagnostic Imaging , Humans , Systematic Reviews as Topic , Databases, Factual , Diagnostic Tests, Routine
17.
Int J Cardiol ; 402: 131889, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38382857

ABSTRACT

OBJECTIVE: To evaluate the diagnostic sensitivity and specificity of ST-segment elevation on a 12­lead ECG in detecting ACO across any coronary artery, challenging the current STEMI-NSTEMI paradigm. METHODS: Studies from MEDLINE and Scopus (2012-2023) comparing ECG findings with coronary angiograms were systematically reviewed and analyzed following PRISMA-DTA guidelines. QUADAS-2 assessed the risk of bias. STUDY SELECTION: Studies included focused on AMI patients and provided data enabling the construction of contingency tables for sensitivity and specificity calculation, excluding those with non-ACS conditions, outdated STEMI criteria, or a specific focus on bundle branch blocks or other complex diagnoses. Data were extracted systematically and pooled test accuracy estimates were computed using MetaDTA software, employing bivariate analyses for within- and between-study variation. The primary outcomes measured were the sensitivity and specificity of ST-segment elevation in detecting ACO. RESULTS: Three studies with 23,704 participants were included. The pooled sensitivity of ST-segment elevation for detecting ACO was 43.6% (95% CI: 34.7%-52.9%), indicating that over half of ACO cases may not exhibit ST-segment elevation. The specificity was 96.5% (95% CI: 91.2%-98.7%). Additional analysis using the OMI-NOMI strategy showed improved sensitivity (78.1%, 95% CI: 62.7%-88.3%) while maintaining similar specificity (94.4%, 95% CI: 88.6%-97.3%). CONCLUSION: The findings reveal a significant diagnostic gap in the current STEMI-NSTEMI paradigm, with over half of ACO cases potentially lacking ST-segment elevation. The OMI-NOMI strategy could offer an improved diagnostic approach. The high heterogeneity and limited number of studies necessitate cautious interpretation and further research in diverse settings.


Subject(s)
Coronary Occlusion , Non-ST Elevated Myocardial Infarction , ST Elevation Myocardial Infarction , Humans , Coronary Occlusion/diagnosis , ST Elevation Myocardial Infarction/diagnosis , Heart , Electrocardiography , Diagnostic Tests, Routine
18.
Curr Urol Rep ; 25(5): 99-107, 2024 May.
Article in English | MEDLINE | ID: mdl-38416321

ABSTRACT

PURPOSE OF REVIEW: Uroflowmetry is widely used for initial non-invasive evaluation of lower urinary tract disorders. Current clinical use is mostly restricted to a scrutiny of the maximum flow rate and uroflow pattern recorded by a conventional flowmeter in a health care facility. There are several advancements in our understanding and in available technologies that promise to transform clinical utilization of this simple test. RECENT FINDINGS: Several aspects of the uroflow test in addition to maximum flow rate and uroflow pattern show potential diagnostic utility. This includes flow acceleration, uroflow indices, uroflow-electromyography including lag time, stop uroflow test, and uroflow-based nomograms. There are initial attempts to use artificial intelligence in analysis. There is also new data with regard to factors influencing variability of uroflow testing that might influence the diagnostic value in as yet uncertain ways including diurnal variability, postural variability, locational variability, and operator variability. There are new technologies for uroflow testing in a home environment allowing for easy repetition. However, there are several challenges owing to a paucity of clinical data and standardization. There are also critical lacunae in terminology that need to be addressed. There are exciting new advancements in the field of uroflowmetry. However, there is need to standardize and validate the newer uroflow tracing analyses and technologies.


Subject(s)
Artificial Intelligence , Urologic Diseases , Humans , Urodynamics , Urinary Bladder , Diagnostic Tests, Routine
19.
Sci Data ; 11(1): 155, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38302487

ABSTRACT

Urinary tract infection (UTI) is a common disorder. Its diagnosis can be made by microscopic examination of voided urine for markers of infection. This manual technique is technically difficult, time-consuming and prone to inter-observer errors. The application of computer vision to this domain has been slow due to the lack of a clinical image dataset from UTI patients. We present an open dataset containing 300 images and 3,562 manually annotated urinary cells labelled into seven classes of clinically significant cell types. It is an enriched dataset acquired from the unstained and untreated urine of patients with symptomatic UTI using a simple imaging system. We demonstrate that this dataset can be used to train a Patch U-Net, a novel deep learning architecture with a random patch generator to recognise urinary cells. Our hope is, with this dataset, UTI diagnosis will be made possible in nearly all clinical settings by using a simple imaging system which leverages advanced machine learning techniques.


Subject(s)
Deep Learning , Urinary Tract Infections , Humans , Diagnostic Tests, Routine , Machine Learning , Microscopy , Urinary Tract Infections/diagnosis , Urinary Tract Infections/drug therapy , Urinary Tract Infections/urine
20.
BMC Med Res Methodol ; 24(1): 28, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38302928

ABSTRACT

BACKGROUND: Selective reporting of results from only well-performing cut-offs leads to biased estimates of accuracy in primary studies of questionnaire-based screening tools and in meta-analyses that synthesize results. Individual participant data meta-analysis (IPDMA) of sensitivity and specificity at each cut-off via bivariate random-effects models (BREMs) can overcome this problem. However, IPDMA is laborious and depends on the ability to successfully obtain primary datasets, and BREMs ignore the correlation between cut-offs within primary studies. METHODS: We compared the performance of three recent multiple cut-off models developed by Steinhauser et al., Jones et al., and Hoyer and Kuss, that account for missing cut-offs when meta-analyzing diagnostic accuracy studies with multiple cut-offs, to BREMs fitted at each cut-off. We used data from 22 studies of the accuracy of the Edinburgh Postnatal Depression Scale (EPDS; 4475 participants, 758 major depression cases). We fitted each of the three multiple cut-off models and BREMs to a dataset with results from only published cut-offs from each study (published data) and an IPD dataset with results for all cut-offs (full IPD data). We estimated pooled sensitivity and specificity with 95% confidence intervals (CIs) for each cut-off and the area under the curve. RESULTS: Compared to the BREMs fitted to the full IPD data, the Steinhauser et al., Jones et al., and Hoyer and Kuss models fitted to the published data produced similar receiver operating characteristic curves; though, the Hoyer and Kuss model had lower area under the curve, mainly due to estimating slightly lower sensitivity at lower cut-offs. When fitting the three multiple cut-off models to the full IPD data, a similar pattern of results was observed. Importantly, all models had similar 95% CIs for sensitivity and specificity, and the CI width increased with cut-off levels for sensitivity and decreased with an increasing cut-off for specificity, even the BREMs which treat each cut-off separately. CONCLUSIONS: Multiple cut-off models appear to be the favorable methods when only published data are available. While collecting IPD is expensive and time consuming, IPD can facilitate subgroup analyses that cannot be conducted with published data only.


Subject(s)
Depression , Tool Use Behavior , Humans , Depression/diagnosis , Sensitivity and Specificity , Psychiatric Status Rating Scales , Diagnostic Tests, Routine
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