Barriers to Point-of-Care Testing in India: Results from Qualitative Research across Different Settings,Users and Major Diseases

Background

Successful point-of-care testing, namely ensuring the completion of the test and treat cycle in the same encounter, has immense potential to reduce diagnostic and treatment delays, and impact patient outcomes. However, having rapid tests is not enough, as many barriers may prevent their successful implementation in point-of-care testing programs. Qualitative research on diagnostic practices may help identify such barriers across different points of care in health systems.

Methods

In this exploratory qualitative study, we conducted 78 semi-structured interviews and 13 focus group discussions in an urban and rural area of Karnataka, India, with healthcare providers (doctors, nurses, specialists, traditional healers, and informal providers), patients, community health workers, test manufacturers, laboratory technicians, program managers and policy-makers. Participants were purposively sampled to represent settings of hospitals, peripheral labs, clinics, communities and homes, in both the public and private sectors.

Results

In the Indian context, the onus is on the patient to ensure successful point-of-care testing across homes, clinics, labs and hospitals, amidst uncoordinated providers with divergent and often competing practices, in settings lacking material, money and human resources. We identified three overarching themes affecting point-of-care testing: the main theme is ‘relationships’ among providers and between providers and patients, influenced by the cross-cutting theme of ‘infrastructure’. Challenges with both result in ‘modified practices’ often favouring empirical (symptomatic) treatment over treatment guided by testing.

Conclusions

Even if tests can be conducted on the spot and infrastructure challenges have been resolved, relationships among providers and between patients and providers are crucial for successful point-of-care testing. Furthermore, these barriers do not act in isolation, but are interlinked and need to be examined as such. Also, a test alone has only limited power to overcome those difficulties. Test developers, policy-makers, healthcare providers and funders need to use these insights in overcoming barriers to point-of-care testing programs.     

Diagnosis of Leptospirosis: Comparison between Microscopic Agglutination Test,IgM-ELISA and IgM Rapid Immunochromatography Test

Background

Leptospirosis is diagnosed on clinical grounds, and confirmed by microscopic agglutination test (MAT). IgM-ELISA (Serion-Virion) and immunochromatography test (Leptocheck-WB) are two immunodiagnostic assays for leptospirosis. Their sensitivity, specificity and applicability in Sri Lanka have not been systematically evaluated.

Methods

Clinically diagnosed leptospirosis patients (n = 919) were recruited from three hospitals in the Western Province of Sri Lanka, during June 2012 to December 2013. MAT, IgM-ELISA and Leptocheck-WB were performed on all patient sera. MAT titer of ≥400 in single sample, four-fold rise or seroconversion ≥100 in paired samples were considered as positive for MAT. For diagnostic confirmation, MAT was performed during both acute and convalescent phases. Anti-leptospiral IgM ≥20 IU/ml and appearance of a band in the test window were considered as positive for IgM-ELISA and Leptocheck-WB test respectively. Patients with an alternative diagnosis (n = 31) were excluded. Data analysis was performed using two methods, i) considering MAT as reference standard and ii) using Bayesian latent class model analysis (BLCM) which considers each test as imperfect.

Results

MAT, IgM-ELISA and Leptocheck-WB positivity were 39.8%, 45.8% and 38.7% respectively during the acute phase. Acute-phase MAT had specificity and sensitivity of 95.7% and 55.3% respectively, when compared to overall MAT positivity. IgM-ELISA and Leptocheck-WB had similar diagnostic sensitivity when compared with acute-phase MAT as the gold standard, although IgM-ELISA showed higher specificity (84.5%) than Leptocheck-WB (73.3%). BLCM analysis showed that IgM-ELISA and Leptocheck-WB had similar sensitivities (86.0% and 87.4%), while acute-phase MAT had the lowest sensitivity (77.4%). However, acute-phase MAT had high specificity (97.6%), while IgM-ELISA and Leptocheck-WB showed similar but lower specificity (84.5% and 82.9%).

Conclusions

Both IgM-ELISA and Leptocheck-WB shows similar sensitivities and specificities. IgM-ELISA may be superior to MAT during the acute phase and suitable for early diagnosis of leptospirosis. Leptocheck-WB is suitable as a rapid immunodiagnostic screening test for resource limited settings.     

Assessment of Haemostasis in Disseminated Intravascular Coagulation by Use of Point-of-Care Assays and Routine Coagulation Tests,in Critically Ill Patients; A Prospective Observational Study

Background

Disseminated intravascular coagulopathy (DIC) relates to the consumption of coagulation factors and platelets with bleeding and micro thrombosis events.

Aim

The aim of this study was to compare haemostasis parameters in critically ill patients with DIC versus patients without DIC, and in survivors versus non-survivors over time. Correlations between the DIC-score, the degree of organ failure and the haemostasis were assessed.

Method

Patients admitted to the intensive care unit with a condition known to be associated with DIC and with an expected length of stay of >3 days were included. Routine laboratory tests, prothrombin time, activated partial thromboplastin time, platelet count, fibrinogen concentration and D-dimer were measured. Coagulation and platelet function were assessed with two point-of-care devices; Multiplate and ROTEM. DIC scores were calculated according to the International Society on Thrombosis and Haemostasis and Japanese Association for Acute Medicine.

Results

Blood was sampled on days 0–1, 2–3 and 4–10 from 136 patients with mixed diagnoses during 290 sampling events. The point-of-care assays indicated a hypocoagulative response (decreased platelet aggregation and reduced clot strength) in patients with DIC and, over time, in non-survivors compared to survivors. Patients with DIC as well as non-survivors had decreased fibrinolysis as shown by ROTEM. DIC scores were higher in non-survivors than in survivors.

Conclusions

Patients with DIC displayed signs of a hypocoagulative response and impaired fibrinolysis, which was also evident over time in non-survivors. Patients with DIC had a higher mortality rate than non-DIC patients, and DIC scores were higher in non-survivors than in survivors.     

The Role of Digital Rectal Examination for Diagnosis of Acute Appendicitis: A Systematic Review and Meta-Analysis

Background

Digital rectal examination (DRE) has been traditionally recommended to evaluate acute appendicitis, although several reports indicate its lack of utility for this diagnosis. No meta-analysis has examined DRE for diagnosis of acute appendicitis.

Objectives

To assess the role of DRE for diagnosis of acute appendicitis.

Data Sources

Cochrane Library, PubMed, and SCOPUS from the earliest available date of indexing through November 23, 2014, with no language restrictions.

Study Selection

Clinical studies assessing DRE as an index test for diagnosis of acute appendicitis.

Data Extraction and Synthesis

Two independent reviewers extracted study data and assessed the quality, using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Bivariate random-effects models were used for the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio (DOR) as point estimates with 95% confidence intervals (CI).

Main Outcomes and Measures

The main outcome measure was the diagnostic performance of DRE for diagnosis of acute appendicitis.

Results

We identified 19 studies with a total of 7511 patients. The pooled sensitivity and specificity were 0.49 (95% CI 0.42–0.56) and 0.61 (95% CI 0.53–0.67), respectively. The positive and negative likelihood ratios were 1.24 (95% CI 0.97–1.58) and 0.85 (95% CI 0.70–1.02), respectively. The DOR was 1.46 (0.95–2.26).

Conclusion and Relevance

Acute appendicitis cannot be ruled in or out through the result of DRE. Reconsideration is needed for the traditional teaching that rectal examination should be performed routinely in all patients with suspected appendicitis.     

Portuguese Family Physicians’ Awareness of Diagnostic and Laboratory Test Costs: A Cross-Sectional Study

Background

Physicians’ ability to make cost-effective decisions has been shown to be affected by their knowledge of health care costs. This study assessed whether Portuguese family physicians are aware of the costs of the most frequently prescribed diagnostic and laboratory tests.

Methods

A cross-sectional study was conducted in a representative sample of Portuguese family physicians, using computer-assisted telephone interviews for data collection. A Likert scale was used to assess physician’s level of agreement with four statements about health care costs. Family physicians were also asked to estimate the costs of diagnostic and laboratory tests. Each physician’s cost estimate was compared with the true cost and the absolute error was calculated.

Results

One-quarter (24%; 95% confidence interval: 23%–25%) of all cost estimates were accurate to within 25% of the true cost, with 55% (95% IC: 53–56) overestimating and 21% (95% IC: 20–22) underestimating the true actual cost. The majority (76%) of family physicians thought they did not have or were uncertain as to whether they had adequate knowledge of diagnostic and laboratory test costs, and only 7% reported receiving adequate education. The majority of the family physicians (82%) said that they had adequate access to information about the diagnostic and laboratory test costs. Thirty-three percent thought that costs did not influence their decision to order tests, while 27% were uncertain.

Conclusions

Portuguese family physicians have limited awareness of diagnostic and laboratory test costs, and our results demonstrate a need for improved education in this area. Further research should focus on identifying whether interventions in cost knowledge actually change ordering behavior, in identifying optimal methods to disseminate cost information, and on improving the cost-effectiveness of care.     

Quantification of Estrogen Receptor-Alpha Expression in Human Breast Carcinomas With a Miniaturized,Low-Cost Digital Microscope: A Comparison with a High-End Whole Slide-Scanner

Introduction

A significant barrier to medical diagnostics in low-resource environments is the lack of medical care and equipment. Here we present a low-cost, cloud-connected digital microscope for applications at the point-of-care. We evaluate the performance of the device in the digital assessment of estrogen receptor-alpha (ER) expression in breast cancer samples. Studies suggest computer-assisted analysis of tumor samples digitized with whole slide-scanners may be comparable to manual scoring, here we study whether similar results can be obtained with the device presented.

Materials and Methods

A total of 170 samples of human breast carcinoma, immunostained for ER expression, were digitized with a high-end slide-scanner and the point-of-care microscope. Corresponding regions from the samples were extracted, and ER status was determined visually and digitally. Samples were classified as ER negative (<1% ER positivity) or positive, and further into weakly (1–10% positivity) and strongly positive. Interobserver agreement (Cohen’s kappa) was measured and correlation coefficients (Pearson’s product-momentum) were calculated for comparison of the methods.

Results

Correlation and interobserver agreement (r = 0.98, p < 0.001, kappa = 0.84, CI95% = 0.75–0.94) were strong in the results from both devices. Concordance of the point-of-care microscope and the manual scoring was good (r = 0.94, p < 0.001, kappa = 0.71, CI95% = 0.61–0.80), and comparable to the concordance between the slide scanner and manual scoring (r = 0.93, p < 0.001, kappa = 0.69, CI95% = 0.60–0.78). Fourteen (8%) discrepant cases between manual and device-based scoring were present with the slide scanner, and 16 (9%) with the point-of-care microscope, all representing samples of low ER expression.

Conclusions

Tumor ER status can be accurately quantified with a low-cost imaging device and digital image-analysis, with results comparable to conventional computer-assisted or manual scoring. This technology could potentially be expanded for other histopathological applications at the point-of-care.     

Differential Diagnosis of Malaria on Truelab Uno?, a Portable,Real-Time,MicroPCR Device for Point-Of-Care Applications

Background

Sensitive and specific detection of malarial parasites is crucial in controlling the significant malaria burden in the developing world. Also important is being able to identify life threatening Plasmodium falciparum malaria quickly and accurately to reduce malaria related mortality. Existing methods such as microscopy and rapid diagnostic tests (RDTs) have major shortcomings. Here, we describe a new real-time PCR-based diagnostic test device at point-of-care service for resource-limited settings.

Methods

Truenat^® Malaria, a chip-based microPCR test, was developed by bigtec Labs, Bangalore, India, for differential identification of Plasmodium falciparum and Plasmodium vivax parasites. The Truenat Malaria tests runs on bigtec’s Truelab Uno^® microPCR device, a handheld, battery operated, and easy-to-use real-time microPCR device. The performance of Truenat^® Malaria was evaluated versus the WHO nested PCR protocol. The Truenat^® Malaria was further evaluated in a triple-blinded study design using a sample panel of 281 specimens created from the clinical samples characterized by expert microscopy and a rapid diagnostic test kit by the National Institute of Malaria Research (NIMR). A comparative evaluation was done on the Truelab Uno^® and a commercial real-time PCR system.

Results

The limit of detection of the Truenat Malaria assay was found to be <5 parasites/μl for both P. falciparum and P. vivax. The Truenat^® Malaria test was found to have sensitivity and specificity of 100% each, compared to the WHO nested PCR protocol based on the evaluation of 100 samples. The sensitivity using expert microscopy as the reference standard was determined to be around 99.3% (95% CI: 95.5–99.9) at the species level. Mixed infections were identified more accurately by Truenat Malaria (32 samples identified as mixed) versus expert microscopy and RDTs which detected 4 and 5 mixed samples, respectively.

Conclusion

The Truenat^® Malaria microPCR test is a valuable diagnostic tool and implementation should be considered not only for malaria diagnosis but also for active surveillance and epidemiological intervention.     

Design,Development and Evaluation of rK28-Based Point-of-Care Tests for Improving Rapid Diagnosis of Visceral Leishmaniasis

Background

Visceral leishmaniasis (VL) is diagnosed by microscopic confirmation of the parasite in bone marrow, spleen or lymph node aspirates. These procedures are unsuitable for rapid diagnosis of VL in field settings. The development of rK39-based rapid diagnostic tests (RDT) revolutionized diagnosis of VL by offering high sensitivity and specificity in detecting disease in the Indian subcontinent; however, these tests have been less reliable in the African subcontinent (sensitivity range of 75–85%, specificity of 70–92%). We have addressed limitations of the rK39 with a new synthetic polyprotein, rK28, followed by development and evaluation of two new rK28-based RDT prototype platforms.

Methodology/Principal Findings

Evaluation of 62 VL-confirmed sera from Sudan provided sensitivities of 96.8% and 93.6% (95% CI = K28: 88.83–99.61%; K39: 84.30–98.21%) and specificities of 96.2% and 92.4% (95% CI = K28: 90.53–98.95%; K39: 85.54–96.65%) for rK28 and rK39, respectively. Of greater interest was the observation that individual VL sera with low rK39 reactivity often had much higher rK28 reactivity. This characteristic of the fusion protein was exploited in the development of rK28 rapid tests, which may prove to be crucial in detecting VL among patients with low rK39 antibody levels. Evaluation of two prototype lateral flow-based rK28 rapid tests on 53 VL patients in Sudan and 73 VL patients in Bangladesh provided promisingly high sensitivities (95.9% [95% CI = 88.46–99.1 in Sudan and 98.1% [95% CI = 89.93–99.95%] in Bangladesh) compared to the rK39 RDT (sensitivities of 86.3% [95% CI = 76.25–93.23%] in Sudan and 88.7% [95% CI = 76.97–95.73%] in Bangladesh).

Conclusions/Significance

Our study compares the diagnostic accuracy of rK39 and rK28 in detecting active VL cases and our findings indicate that rK28 polyprotein has great potential as a serodiagnostic tool. A new rK28-based RDT will prove to be a valuable asset in simplifying VL disease confirmation at the point-of-care.     

Evaluation of a Rapid Point of Care Test for Detecting Acute and Established HIV Infection,and Examining the Role of Study Quality on Diagnostic Accuracy: A Bayesian Meta-Analysis

Introduction

Fourth generation (Ag/Ab combination) point of care HIV tests like the FDA-approved Determine HIV1/2 Ag/Ab Combo test offer the promise of timely detection of acute HIV infection, relevant in the context of HIV control. However, a synthesis of their performance has not yet been done. In this meta-analysis we not only assessed device performance but also evaluated the role of study quality on diagnostic accuracy.

Methods

Two independent reviewers searched seven databases, including conferences and bibliographies, and independently extracted data from 17 studies. Study quality was assessed with QUADAS-2. Data on sensitivity and specificity (overall, antigen, and antibody) were pooled using a Bayesian hierarchical random effects meta-analysis model. Subgroups were analyzed by blood samples (serum/plasma vs. whole blood) and study designs (case-control vs. cross-sectional).

Results

The overall specificity of the Determine Combo test was 99.1%, 95% credible interval (CrI) [97.3–99.8]. The overall pooled sensitivity for the device was at 88.5%, 95% [80.1–93.4]. When the components of the test were analyzed separately, the pooled specificities were 99.7%, 95% CrI [96.8–100] and 99.6%, 95% CrI [99.0–99.8], for the antigen and antibody components, respectively. Pooled sensitivity of the antibody component was 97.3%, 95% CrI [60.7–99.9], and pooled sensitivity for the antigen component was found to be 12.3%, 95% (CrI) [1.1–44.2]. No significant differences were found between subgroups by blood sample or study design. However, it was noted that many studies restricted their study sample to p24 antigen or RNA positive specimens, which may have led to underestimation of overall test performance. Detection bias, selection (spectrum) bias, incorporation bias, and verification bias impaired study quality.

Conclusions

Although the specificity of all test components was high, antigenic sensitivity will merit from an improvement. Besides the accuracy of the device itself, study quality, also impacts the performance of the test. These factors must be kept in mind in future evaluations of an improved device, relevant for global scale up and implementation.     

Are Treponema pallidum Specific Rapid and Point-of-Care Tests for Syphilis Accurate Enough for Screening in Resource Limited Settings? Evidence from a Meta-Analysis

Background

Rapid and point-of-care (POC) tests for syphilis are an invaluable screening tool, yet inadequate evaluation of their diagnostic accuracy against best reference standards limits their widespread global uptake. To fill this gap, a systematic review and meta-analysis was conducted to evaluate the sensitivity and specificity of rapid and POC tests in blood and serum samples against Treponema pallidum (TP) specific reference standards.

Methods

Five electronic databases (1980–2012) were searched, data was extracted from 33 articles, and Bayesian hierarchical models were fit.

Results

In serum samples, against a TP specific reference standard point estimates with 95% credible intervals (CrI) for the sensitivities of popular tests were: i) Determine, 90.04% (80.45, 95.21), ii) SD Bioline, 87.06% (75.67, 94.50), iii) VisiTect, 85.13% (72.83, 92.57), and iv) Syphicheck, 74.48% (56.85, 88.44), while specificities were: i) Syphicheck, 99.14% (96.37, 100), ii) Visitect, 96.45% (91.92, 99.29), iii) SD Bioline, 95.85% (89.89, 99.53), and iv) Determine, 94.15% (89.26, 97.66). In whole blood samples, sensitivities were: i) Determine, 86.32% (77.26, 91.70), ii) SD Bioline, 84.50% (78.81, 92.61), iii) Syphicheck, 74.47% (63.94, 82.13), and iv) VisiTect, 74.26% (53.62, 83.68), while specificities were: i) Syphicheck, 99.58% (98.91, 99.96), ii) VisiTect, 99.43% (98.22, 99.98), iii) SD Bioline, 97.95%(92.54, 99.33), and iv) Determine, 95.85% (92.42, 97.74).

Conclusions

Rapid and POC treponemal tests reported sensitivity and specificity estimates comparable to laboratory-based treponemal tests. In resource limited settings, where access to screening is limited and where risk of patients lost to follow up is high, the introduction of these tests has already been shown to improve access to screening and treatment to prevent stillbirths and neonatal mortality due to congenital syphilis. Based on the evidence, it is concluded that rapid and POC tests are useful in resource limited settings with poor access to laboratories or screening for syphilis.     

Intestinal Fatty Acid-Binding Protein as a Diagnostic Marker for Complicated and Uncomplicated Necrotizing Enterocolitis: A Prospective Cohort Study

Background

Early NEC symptoms are non-specific and diagnostic tests lack discriminative power. Intestinal fatty acid-binding protein (I-FABP), mainly located in small bowel enterocytes, is released into the blood following NEC-associated enterocyte disruption. Aim of this prospective cohort trial was to determine the diagnostic value of I-FABP measured in plasma (I-FABPp) and urine (I-FABPu) for the presence of NEC, to evaluate I-FABP levels during NEC development, and to assess its prognostic value for the progression from suspected to complicated disease.

Methods

Between 2010 and 2012 we prospectively enrolled neonates with suspected NEC. We measured I-FABP levels eight-hourly from onset of suspected NEC for at least 48 hours, or until surgery. NEC diagnosis was confirmed radiologically or during operation. We defined NEC as complicated if it resulted in surgery and/or death. We determined disease course and diagnostic I-FABP cut-off points.

Results

The study comprised 37 neonates (24M, 13F), gestational age 28 (24–36) weeks, birth weight 1190 (570–2,400) grams. We found significantly higher I-FABPp and I-FABPu levels in NEC patients (n = 22) than in patients with other diagnoses (n = 15). Cut-off values for diagnosing NEC were 9 ng/mL I-FABPp and 218 ng/mL I-FABPu, with corresponding likelihood ratios (LRs) of 5.6 (95% CI 0.89–35) and 5.1 (95% CI 0.73–36), respectively. I-FABP levels were highest in the first eight hours after symptom onset and gradually decreased over time. Cut-off values for complicated disease were 19 ng/mL I-FABPp and 232 ng/mL I-FABPu, with LRs of 10 (95% CI 1.6–70) and 11 (95% CI 1.6–81), respectively.

Conclusions

Both plasma and urinary I-FABP levels specifically identify NEC in preterm infants prior to appearance of diagnostic radiological signs suggestive for NEC. Moreover, serial I-FABP measurements accurately predict development of complicated disease.     

Identifying Patients with Bacteremia in Community-Hospital Emergency Rooms: A Retrospective Cohort Study

Objectives

(1) To develop a clinical prediction rule to identify patients with bacteremia, using only information that is readily available in the emergency room (ER) of community hospitals, and (2) to test the validity of that rule with a separate, independent set of data.

Design

Multicenter retrospective cohort study.

Setting

To derive the clinical prediction rule we used data from 3 community hospitals in Japan (derivation). We tested the rule using data from one other community hospital (validation), which was not among the three “derivation” hospitals.

Participants

Adults (age ≥ 16 years old) who had undergone blood-culture testing while in the ER between April 2011 and March 2012. For the derivation data, n = 1515 (randomly sampled from 7026 patients), and for the validation data n = 467 (from 823 patients).

Analysis

We analyzed 28 candidate predictors of bacteremia, including demographic data, signs and symptoms, comorbid conditions, and basic laboratory data. Chi-square tests and multiple logistic regression were used to derive an integer risk score (the “ID-BactER” score). Sensitivity, specificity, likelihood ratios, and the area under the receiver operating characteristic curve (i.e., the AUC) were computed.

Results

There were 241 cases of bacteremia in the derivation data. Eleven candidate predictors were used in the ID-BactER score: age, chills, vomiting, mental status, temperature, systolic blood pressure, abdominal sign, white blood-cell count, platelets, blood urea nitrogen, and C-reactive protein. The AUCs was 0.80 (derivation) and 0.74 (validation). For ID-BactER scores ≥ 2, the sensitivities for derivation and validation data were 98% and 97%, and specificities were 20% and 14%, respectively.

Conclusions

The ID-BactER score can be computed from information that is readily available in the ERs of community hospitals. Future studies should focus on developing a score with a higher specificity while maintaining the desired sensitivity.     

Modifiable Prognostic Factors of Hepatocellular Carcinoma in Patients with Non-Surgical Treatment

Background & aims

Current hepatocellular carcinoma (HCC) staging systems only use baseline characteristics to predict outcome. We aimed to explore modifiable factors of the prognosis in HCC cases had undergone non-surgical treatment.

Methods

All HCC cases in Kaohsiung Chang Gung Memorial hospital in southern Taiwan from 2002 to 2012 must met all below criteria: (1) met international diagnostic guidelines, (2) underwent the initial treatments in our hospital (3) treated by non-surgical treatment modalities and (4) survived more than two years, with follow-up time longer than five years.

Results

A total 698 patients were enrolled: 451 (24.6%, group A) survivied between 2 to 5 years, and 247 (13.5%, group B) had survived > 5 years. Aside from liver function reserve and BCLC stages, four interventional factors: initial treatment modality, outcomes of 1^st or 2^nd treatment, and anti-viral therapy to chronic viral hepatitis were associated with prognosis. After propensity score matching, multiple logistic regression of 223 well-matched pairs showed that recurrence within one year after 1^st treatment (OR: 2.17, 95% CI: 1.35–3.48), incomplete 2^nd treatment (2.01, 1.27–3.17) and absence of anti-viral agents (1.68, 1.09–2.59) were independent poor prognostic factors.

Conclusion

Complete treatment and anti-viral agents to chronic hepatitis were both independent modifiable prognostic factors of HCC patients had undergone non-surgical treatment. Based on these findings, timely treatment to achieve maximal locoregional control and anti-viral treatment should be provided as possible.     

Inaccurate Diagnosis of HIV-1 Group M and O Is a Key Challenge for Ongoing Universal Access to Antiretroviral Treatment and HIV Prevention in Cameroon

Background

Increased access to HIV testing is essential in working towards universal access to HIV prevention and treatment in resource-limited countries. We here evaluated currently used HIV diagnostic tests and algorithms in Cameroon for their ability to correctly identify HIV infections.

Methods

We estimated sensitivity, specificity, and positive and negative predictive values of 5 rapid/simple tests, of which 3 were used by the national program, and 2 fourth generation ELISAs. The reference panel included 500 locally collected samples; 187 HIV -1 M, 10 HIV-1 O, 259 HIV negative and 44 HIV indeterminate plasmas.

Results

None of the 5 rapid assays and only 1 ELISA reached the current WHO/UNAIDS recommendations on performance of HIV tests of at least 99% sensitivity and 98% specificity. Overall, sensitivities ranged between 94.1% and 100%, while specificities were 88.0% to 98.8%. The combination of all assays generated up to 9% of samples with indeterminate HIV status, because they reacted discordantly with at least one of the different tests. Including HIV indeterminate samples in test efficiency calculations significantly decreased specificities to a range from 77.9% to 98.0%. Finally, two rapid assays failed to detect all HIV-1 group O variants tested, with one rapid test detecting only 2 out of 10 group O specimens.

Conclusion

In the era of ART scaling-up in Africa, significant proportions of false positive but also false negative results are still observed with HIV screening tests commonly used in Africa, resulting in inadequate treatment and prevention strategies. Depending on tests or algorithms used, up to 6% of HIV-1 M and 80% of HIV-1 O infected patients in Cameroon do not receive ART and adequate counseling to prevent further transmission due to low sensitivities. Also, the use of tests with low specificities could imply inclusion of up to 12% HIV negative people in ART programs and increase budgets in addition to inconveniences caused to patients.     

Diffusion-Weighted Imaging in 3.0 Tesla Breast MRI: Diagnostic Performance and Tumor Characterization Using Small Subregions vs. Whole Tumor Regions of Interest

Introduction

Apparent diffusion coefficient (ADC) values are increasingly reported in breast MRI. As there is no standardized method for ADC measurements, we evaluated the effect of the size of region of interest (ROI) to diagnostic utility and correlation to prognostic markers of breast cancer.

Methods

This prospective study was approved by the Institutional Ethics Board; the need for written informed consent for the retrospective analyses of the breast MRIs was waived by the Chair of the Hospital District. We compared diagnostic accuracy of ADC measurements from whole-lesion ROIs (WL-ROIs) to small subregions (S-ROIs) showing the most restricted diffusion and evaluated correlations with prognostic factors in 112 consecutive patients (mean age 56.2±11.6 years, 137 lesions) who underwent 3.0-T breast MRI.

Results

Intra- and interobserver reproducibility were substantial (κ = 0.616–0.784; Intra-Class Correlation 0.589–0.831). In receiver operating characteristics analysis, differentiation between malignant and benign lesions was excellent (area under curve 0.957–0.962, cut-off ADC values for WL-ROIs: 0.87×10⁻³ mm²s^-1; S-ROIs: 0.69×10⁻³ mm²s^-1, P<0.001). WL-ROIs/S-ROIs achieved sensitivities of 95.7%/91.3%, specificities of 89.5%/94.7%, and overall accuracies of 89.8%/94.2%. In S-ROIs, lower ADC values correlated with presence of axillary metastases (P = 0.03), high histological grade (P = 0.006), and worsened Nottingham Prognostic Index Score (P<0.05). In both ROIs, ADC values correlated with progesterone receptors and advanced stage (P<0.01), but not with HER2, estrogen receptors, or Ki-67.

Conclusions

ADC values assist in breast tumor characterization. Small ROIs were more accurate than whole-lesion ROIs and more frequently associated with prognostic factors. Cut-off values differed significantly depending on measurement procedure, which should be recognized when comparing results from the literature. Instead of using a whole lesion covering ROI, a small ROI could be advocated in diffusion-weighted imaging.     

Diagnostic Accuracy of Natriuretic Peptides for Heart Failure in Patients with Pleural Effusion: A Systematic Review and Updated Meta-Analysis

Background

Previous studies have reported that natriuretic peptides in the blood and pleural fluid (PF) are effective diagnostic markers for heart failure (HF). These natriuretic peptides include N-terminal pro-brain natriuretic peptide (NT-proBNP), brain natriuretic peptide (BNP), and midregion pro-atrial natriuretic peptide (MR-proANP). This systematic review and meta-analysis evaluates the diagnostic accuracy of blood and PF natriuretic peptides for HF in patients with pleural effusion.

Methods

PubMed and EMBASE databases were searched to identify articles published in English that investigated the diagnostic accuracy of BNP, NT-proBNP, and MR-proANP for HF. The last search was performed on 9 October 2014. The quality of the eligible studies was assessed using the revised Quality Assessment of Diagnostic Accuracy Studies tool. The diagnostic performance characteristics (sensitivity, specificity, and other measures of accuracy) were pooled and examined using a bivariate model.

Results

In total, 14 studies were included in the meta-analysis, including 12 studies reporting the diagnostic accuracy of PF NT-proBNP and 4 studies evaluating blood NT-proBNP. The summary estimates of PF NT-proBNP for HF had a diagnostic sensitivity of 0.94 (95% confidence interval [CI]: 0.90–0.96), specificity of 0.91 (95% CI: 0.86–0.95), positive likelihood ratio of 10.9 (95% CI: 6.4–18.6), negative likelihood ratio of 0.07 (95% CI: 0.04–0.12), and diagnostic odds ratio of 157 (95% CI: 57–430). The overall sensitivity of blood NT-proBNP for diagnosis of HF was 0.92 (95% CI: 0.86–0.95), with a specificity of 0.88 (95% CI: 0.77–0.94), positive likelihood ratio of 7.8 (95% CI: 3.7–16.3), negative likelihood ratio of 0.10 (95% CI: 0.06–0.16), and diagnostic odds ratio of 81 (95% CI: 27–241). The diagnostic accuracy of PF MR-proANP and blood and PF BNP was not analyzed due to the small number of related studies.

Conclusions

BNP, NT-proBNP, and MR-proANP, either in blood or PF, are effective tools for diagnosis of HF. Additional studies are needed to rigorously evaluate the diagnostic accuracy of PF and blood MR-proANP and BNP for the diagnosis of HF.     

Role of QuantiFERON-TB Gold,Interferon Gamma Inducible Protein-10 and Tuberculin Skin Test in Active Tuberculosis Diagnosis

Background

The measurement of Interferon gamma or Interferon gamma inducible protein (IP)-10 in antigen stimulated blood samples is suggested as an alternative method for latent tuberculosis (TB) diagnosis. Nonetheless, their role in active TB diagnosis, particularly in TB endemic settings is yet to be defined. In this study, the sensitivities and specificities of Interferon gamma release assay (IGRA), IP-10 assay and tuberculin skin test (TST) in detecting active TB cases were assessed in human immunodeficiency virus (HIV) sero-negative TB patients and healthy controls respectively.

Methods/Principal Findings

A total of 177 adult TB patients and 100 healthy controls were included for this study. QuantiFERON-TB Gold In-tube (QFT-IT) method was used to analyze the sensitivity and specificity of IGRA. QFT-IT, IP-10 and TST yielded the diagnostic sensitivities of 90.6% (95%CI: 86.3%–94.9%), 92.5% (95%CI: 88.6%–96.4%) and 68.9% (95%CI: 60.6%–77.2%) and specificities of 55% (95% CI: 35.2%–54.8%), 48% (95% CI: 38.2%–57.8%) and 75.5% (95% CI: 66.8%–84.2%), respectively. The extent of pulmonary involvement or presence of diabetes mellitus did not appear to influence the sensitivities of any of these tests. The combination of any of the two tests among QFT-IT, IP-10 and TST showed >98% sensitivity among smear negative cases and particularly the combination of IP-10, TST and smear microscopy showed 100% sensitivity, however, the specificity was decreased to 44.8%.

Conclusions/Significance

QFT-IT and IP-10 were highly sensitive in detecting active TB cases. The combination with TST improved the sensitivity of QFT-IT and IP-10 significantly. Although the higher sensitivity of combination of QFT-IT/IP-10 and TST may be useful in active TB diagnosis, they are limited by their poor specificity due to the high prevalence of latent TB in our settings.     

Evaluation of Multiparametric Magnetic Resonance Imaging in Detection and Prediction of Prostate Cancer

Background

Although European Society of Urogenital Radiology proposed the potential of multiparametric magnetic resonance imaging (MP-MRI) as a tool in the diagnostic pathway for prostate cancer (PCa) and published a unified scoring system named Prostate Imaging Reporting and Data System (PI-RADS version 1), these still need to be validated by real-life studies.

Objective

To evaluate the role of MP-MRI in detection and prediction of PCa.

Methods

Patients with clinical suspicion of PCa who underwent prebiopsy MP-MRI from 2002 to 2009 were recruited. MP-MRI results were retrospectively assigned as overall scores using PI-RADS by two radiologists. Patients were followed and the end point was the diagnosis of PCa. Receiver operating characteristics (ROC) curve was performed to test diagnostic efficacy of MP-MRI, under results of biopsy within three months. The cox proportional hazards model was used to identify independent variables for the detection of PCa.

Results

Finally, 1113 of the 1806 enrolled patients were included for analysis. The median follow-up was 56.0 months (1–137 mo). For 582 patients biopsied within three months, area under the curve for the detection of PCa with MP-MRI was 0.88 (95% confidence interval [CI], 0.75–1.00) in group of baseline prostate specific antigen (PSA) 0.01–4.00 ng/ml (n = 31), 0.90 (95% CI, 0.84–0.95) in PSA 4.01–10.00 ng/ml (n = 142), and 0.91 (95% CI, 0.87–0.94) in PSA >10.00 ng/ml (n = 409), respectively. In the cox model adjusted for age and baseline PSA level, for the detection rate of PCa, compared with PI-RADS 1–2 (reference), the hazard ratio was 6.43 (95% CI, 4.29–9.65) for PI-RADS 3, 18.58 (95% CI, 13.36–25.84) for PI-RADS 4–5 (p < 0.001).

Conclusions

Prebiopsy MP-MRI with PI-RADS is demonstrated as a valuable diagnostic and predictive tool for PCa.     

Diagnostic Efficacy of Magnifying Endoscopy with Narrow-Band Imaging for Gastric Neoplasms: A Meta-Analysis

Background

Magnifying endoscopy with narrow-band imaging (ME-NBI) is a novel, image-enhanced endoscopic technique for differentiating gastrointestinal neoplasms and potentially enabling pathological diagnosis.

Objectives

The aim of this analysis was to assess the diagnostic performance of ME-NBI for gastric neoplasms.

Methods

We performed a systematic search of the PubMed, EMbase, Web of Science, and Cochrane Library databases for relevant studies. Meta-DiSc (version 1.4) and STATA (version 11.0) software were used for the data analysis. Random effects models were used to assess diagnostic efficacy. Heterogeneity was tested by the Q statistic and I² statistic. Meta-regression was used to analyze the sources of heterogeneity.

Results

A total of 10 studies, with 2151 lesions, were included. The pooled characteristics of these studies were as follows: sensitivity 0.85 (95% confidence interval [CI]: 0.81–0.89), specificity 0.96 (95% confidence interval [CI]: 0.95–0.97), and area under the curve (AUC) 0.9647. In the subgroup analysis, which compared the diagnostic efficacy of ME-NBI and white light imaging (WLI), the pooled sensitivity and specificity of ME-NBI were 0.87 (95% CI: 0.80–0.92) and 0.93 (95% CI: 0.90–0.95), respectively, and the area under the curve (AUC) was 0.9556. In contrast, the pooled sensitivity and specificity of WLI were 0.61 (95% CI: 0.53–0.69) and 0.65 (95% CI: 0.60–0.69), respectively, and the area under the curve (AUC) was 0.6772.

Conclusions

ME-NBI presents a high diagnostic value for gastric neoplasms and has a high specificity.