The RAPIDO trial-Reduction in disease-related treatment failure does not translate into improved overall survival: a mystery solved!

The initial publication of the RAPIDO trial resulted in widespread adoption of short-course radiotherapy and consolidation chemotherapy in locally advanced rectal cancer. The impressive reduction in disease-related treatment failure did not, however, translate into any overall survival benefit. The recent update of the RAPIDO trial with its 5-year results provides much insight into the actual effect that this approach has on patient outcomes and the detriment in local control leads to the question as to whether this approach can still be considered as standard of care in high-risk rectal cancer.

In house-development of a rapid immunochromatographic test for the detection of Escherichia coli in urine samples.

Urinary tract infections (UTIs) are a common health concern. Urine culture is the "gold standard" for UTI diagnosis but takes 48h. Rapid methods like dipstick tests are used as point-of-care tests. However, their sensitivity and specificity are variable. In this work, a rapid immunochromatographic test (IT) for detecting Escherichia coli in urine was developed, and its performance was evaluated in urine samples from patients with suspected UTI. The "universal lateral flow assay kit" was employed using an E. coli capture antibody. One hundred and five (105) urine samples were analyzed using the IT, dipstick test, and urine culture. The sensitivity of the IT was 74.5%, specificity 88.9%, positive predictive value (PPV) 86.3%, and negative predictive value (NPV) 78.7%. The combination of the IT with the dipstick test increases sensitivity to 94.1%, specificity to 66.7%, PPV to 72.7%, and NPV to 92.3%. Using the IT for detecting E. coli in urine could be a valuable technique for UTI screening, showing better specificity and diagnostic precision but lower sensitivity than the dipstick test. Based on these results, we propose that the combined use of both screening techniques would allow a rapid and more precise diagnosis of UTI, rationalizing the indication for empirical antibiotics.

Is short-course radiotherapy and total neoadjuvant therapy the new standard of care in locally advanced rectal cancer? A sensitivity analysis of the RAPIDO clinical trial.

BACKGROUND: The results of the RAPIDO trial have been accepted as evidence in favour of short-course radiotherapy (SC-RT) followed by chemotherapy before total mesorectal excision in high-risk locally advanced rectal cancer. A noteworthy concern is that the RAPIDO trial did not ensure that all patients in the control arm received adjuvant chemotherapy. This may bias statistical estimates in favour of the experimental arm if adjuvant chemotherapy is active in rectal cancer. Moreover, the 5-year update revealed an increase in the risk of local relapse in the experimental arm. MATERIALS AND METHODS: We carried out sensitivity analyses to determine how plausible effects of adjuvant chemotherapy, adjusted by the proportion of patients in the standard arm receiving adjuvant treatment, would have influenced the observed treatment effect estimate of the RAPIDO trial. The most plausible values for the benefit of adjuvant chemotherapy were determined by Bayesian re-analysis of a prior meta-analysis. RESULTS: The meta-analysis suggested that oxaliplatin/fluorouracil-based adjuvant chemotherapy may improve disease-free survival (DFS) in rectal cancer although the signal is weak [hazard ratio (HR) 0.84, 95% credible interval, 0.57-1.15]; probability of benefit (HR <1) was 91.2%. In the sensitivity analysis, the HR for disease-related treatment failure would remain <1, thus favouring total neoadjuvant therapy (TNT), on most occasions, but the null hypothesis would not have been rejected in various credible settings. For the RAPIDO data to be consistent with the null effect, a moderate benefit of adjuvant chemotherapy (HR for DFS between 0.75 and 0.80) and 70%-80% of exposed participants would suffice. CONCLUSION: The decision to make adjuvant chemotherapy optional in the standard arm may have biased the results in favour of the experimental arm, in a scenario in which TNT does not offset the increase in local recurrences after SC-RT.

Rapid antigen tests for the detection of SARS-CoV-2: A narrative review.

The rapid identificationand isolation of COVID-19 patients has become the cornerstone for the control of the recent outbreak. Real-time quantitative polymerase chain reaction is routinely used to confirm COVID-19 diagnosis and is considered the gold standard due to high sensitivity and specificity. Nevertheless, it usually takes several days and a relatively higher cost. Antigen tests based have emerged to cope with such disadvantages, by offering rapid results, an easy-to-use procedure, and low costs. The objective of the narrative review was to provide up-to-date data about CE-marked rapid antigen tests (RATs) for COVID-19. Given their large number, the study only focused on representative and widely used in Spain (Standard Q, Nadal, Panbio, CerTest, and Wondfo). RATs have become a very useful and validated tool for controlling the spread of COVID-19 allowing the rapid identification of active infection and isolation of positive patients. The present revision of the literature has demonstrated that sensitivity and specificity of all available RATs in Spain are high and accomplish European regulations and WHO recommendations.

Incorporation of the rapid HIV test in a sexually-transmitted disease clinic in Buenos Aires: Dramatic increase in the frequency of HIV diagnosis.

Improving access to diagnosis constitutes a key step in the control of the Human immunodeficiency virus (HIV)/AIDS epidemic. Rapid testing is increasingly gaining interest as a powerful diagnostic tool to achieve this goal. The purpose of this study was to implement the rapid HIV test (RHT) in a clinical setting in order to evaluate its effectiveness in increasing HIV diagnosis and patient linkage to the healthcare system. The RHT was offered to all patients attending a sexually-transmitted disease clinic in the City of Buenos Aires between March and December 2015. A total of 593 RHT were performed. The implementation of the RHT yielded an increase in frequency of diagnosis from 6.9% to 31.4% (p<0.001). The first steps of the care cascade showed high retention rates around 90%. RHT yielded an HIV prevalence of 6.3% (95% CI: 4.2-8.5) in this population. HIV prevalence tended to be higher in individuals with no previous HIV testing (p=0.09). Linkage to the healthcare system was associated with a higher probability of having been tested for HIV (p=0.008). The incorporation of the RHT resulted in a high retention of patients and an increase in both frequency of diagnosis and results reception when compared to the classic methodology.

Molecular methods for septicemia diagnosis. / Métodos moleculares para el diagnóstico de septicemia.

Septicemia remains a major cause of hospital mortality. Blood culture remains the best approach to identify the etiological microorganisms when a bloodstream infection is suspected but it takes long time because it relies on bacterial or fungal growth. The introduction in clinical microbiology laboratories of the matrix-assisted laser desorption ionization time-of-flight mass spectrometry technology, DNA hybridization, microarrays or rapid PCR-based test significantly reduce the time to results. Tests for direct detection in whole blood samples are highly desirable because of their potential to identify bloodstream pathogens without waiting for blood cultures to become positive. Nonetheless, limitations of current molecular diagnostic methods are substantial. This article reviews these new molecular approaches (LightCycler SeptiFast, Magicplex sepsis real time, Septitest, VYOO, PCR/ESI-MS analysis, T2Candida).

Rapid methods for detection of bacterial resistance to antibiotics. / Métodos rápidos para la detección de la resistencia bacteriana a antibióticos.

The most widely used antibiotic susceptibility testing methods in Clinical Microbiology are based on the phenotypic detection of antibiotic resistance by measuring bacterial growth in the presence of the antibiotic being tested. These conventional methods take typically 24hours to obtain results. Here we review the main techniques for rapid determination of antibiotic susceptibility. Data obtained with different methods such as molecular techniques, microarrays, commercial methods used in work routine, immunochromatographic methods, colorimetric methods, image methods, nephelometry, MALDI-TOF mass spectrometry, flow cytometry, chemiluminescence and bioluminescence, microfluids and methods based on cell disruption are analysed in detail.

Estimated saving of antibiotics in pharyngitis and lower respiratory tract infections if general practitioners used rapid tests and followed guidelines.

INTRODUCTION: General practitioners (GP) in Spain do not have access to rapid tests and adherence to guidelines is usually suboptimal. The aim of the study is to evaluate the estimated number of antibiotics that could have been saved if GPs had appropriately used these tests and had followed the guidelines. DESIGN: Observational study. SETTING: Primary care centres from eight Autonomous Communities in Spain. PARTICIPANTS: GPs who had not participated in previous studies on rational use of antibiotics. INTERVENTION: GPs registered all the cases of pharyngitis and lower respiratory tract infections (LRTI) during 15 working days in 2015, by means of a 47-item audit. MAIN MEASUREMENTS: Actual GPs' antibiotic prescription and estimated number of antibiotics that could have been saved according to recent guidelines. RESULTS: A total of 126 GPs registered 1012 episodes of pharyngitis and 1928 LRTIs. Antibiotics were given or patients were referred in 497 patients with pharyngitis (49.1%) and 963 patients with LRTI (49.9%). If GPs had appropriately used rapid antigen detection tests and C-reactive protein tests and had strictly followed current guidelines, antibiotics would have been given to 7.6% and 15.1%, respectively, with an estimated saving of 420 antibiotics in patients with sore throat (estimated saving of 84.5%; 95% CI: 81.1-87.4%) and 672 antibiotics in LRTIs (estimated saving of 69.8%,95% CI: 67.1-72.5%). CONCLUSIONS: GP adherence to guidelines and a correct introduction of rapid tests in clinical practice in Spain could result in a considerable saving of unnecessary prescription of antibiotics in pharyngitis and LRTIs.

[Recommendations for the use of rapid diagnosis techniques in respiratory infections in primary care]. / Recomendaciones de utilización de técnicas de diagnóstico rápido en infecciones respiratorias en atención primaria.

Respiratory tract infections rank first as causes of adult and paediatric infectious morbidity in primary care in Spain. These infections are usually self-limiting and are mainly caused by viruses. However, a high percentage of unnecessary antibiotic prescription is reported. Point-of-care tests are biomedical tests, which can be used near the patient, without interference of a laboratory. The use of these tests, many of which have been recently developed, is rapidly increasing in general practice. Notwithstanding, we must mull over whether they always contribute to an effective and high-quality diagnostic process by primary care clinicians. We present a set of criteria that can be used by clinicians and discuss the pros and cons of the instruments available for the management of respiratory tract infections and how to use them appropriately.

Evaluation of two rapid screening assays for detecting hepatitis C antibodies in resource-constrained settings.

OBJECTIVE: To evaluate the diagnostic accuracy of the OraQuick HCV rapid antibody test from OraSure and the Multisure HCV antibody assay from MP Biomedicals. METHODS: Five seropanels from patients, intravenous drug users and blood donors with and without HCV infection were used on the two rapid immunochromatographic tests. Sensitivity, specificity and predictive values were calculated. In addition, seropanels from 10 seroconverters were used to assess early identification of HCV infection. The study was undertaken in a laboratory at Paul Ehrlich Institute in Germany. RESULTS: Panel 1 contained of 55 positive and 25 negative samples. The OraQuick HCV test had a sensitivity of 100% (95% CI: 93.5-100) and a specificity of 100% (95% CI: 86.3-100). The Multisure HCV test had a sensitivity of 100% (95% CI: 93.5-100) and a specificity of 96% (95% CI: 79.6-99.9). Panel 2 consisted of 193 pre-characterised anti-HCV-positive patient samples. The OraQuick HCV test identified 191 samples correctly and the Multisure HCV 192. The sensitivity was 99.0% (95% CI: 96.3-99.9) for the OraQuick HCV test and 99.5% (95% CI: 97.1-100) for the Multisure HCV test. Panel 3 was composed of seroconversion samples of 10 patients. The OraQuick HCV test detected all of these 10 infections while the Multisure HCV test detected six and was indeterminate on 2. Panel 4 included 53 anti-HCV negative blood samples from blood donors. Both tests correctly identified all 53. Panel 5 consisted of 26 samples of HCV/HIV co-infected patients. The sensitivity of the OraQuick HCV test was 65.2% (95% CI: 42.8-82.8) after 20 min and 73.9% (95% CI: 51.3-88.9) after 40 min of incubation. The Multisure HCV test had a sensitivity of 96.2% (95% CI: 80.4-99.9). CONCLUSION: This evaluation revealed good sensitivity for both rapid screening assays. The detection of seroconverters, however, was lower in the MutiSure HCV test. Therefore the MultiSure test should be used with hesitation in high incidence settings. The OraQuick gave HCV false-negative results in almost 25% of the HIV-positive sera. Therefore may the OraQuick be less suited in HIV prevalent areas.

A two-hour antibiotic susceptibility test by ATP-bioluminescence.

The antibiotic susceptibility test (AST) in Clinical Microbiology laboratories is still time-consuming, and most procedures take 24h to yield results. In this study, a rapid antimicrobial susceptibility test using ATP-bioluminescence has been developed. The design of method was performed using five ATCC collection strains of known susceptibility. This procedure was then validated against standard commercial methods on 10 strains of enterococci, 10 staphylococci, 10 non-fermenting gram negative bacilli, and 13 Enterobacteriaceae from patients. The agreement obtained in the sensitivity between the ATP-bioluminescence method and commercial methods (E-test, MicroScan and VITEK2) was 100%. In summary, the preliminary results obtained in this work show that the ATP-bioluminescence method could provide a fast and reliable AST in two hours.

Evaluation of a new rapid diagnostic test for the detection of influenza and RSV.

INTRODUCTION: Influenza viruses and respiratory syncytial virus (RSV) can cause an acute respiratory disease that occurs seasonally in epidemic waves. This retrospective study was conducted to evaluate the Sofia(®) Influenza A+B and the Sofia(®) RSV fluorescence immunoassays (FIAs), two novel rapid detection tests (RDTs) for influenza A and B and RSV. METHODS: Two hundred and nine breath samples were selected from patients with respiratory symptoms determined to be positive/negative for influenza A, influenza B or RSV using one of the reference diagnostic techniques, cell culture and/or RT-PCR (Simplexa™Flu A/B & RSV). The Sofia Influenza A+B FIA was tested on 123 samples (63 from children and 60 from adults) and the Sofia RSV FIA was tested on 86 pediatric samples. Sensitivity and specificity values of both assays were calculated assuming the reference techniques as the gold standard. RESULTS: Sensitivity and specificity values for the Sofia Influenza A+B FIA were 73.1% and 97.8%, respectively. Sensitivity and specificity values for the Sofia RSV FIA were 87.5% and 86.7%, respectively. CONCLUSION: The sensitivity results obtained for the two assays were considerably higher than those reported for other RDTs. In conclusion, the Sofia Influenza A+B and the Sofia RSV FIAs are appropriate tools for the rapid diagnosis of these viruses.

[Rapid antibiotic susceptibility test in Clinical Microbiology]. / Antibiograma rápido en Microbiología Clínica.

The most widely used antibiotic susceptibility testing methods in Clinical Microbiology are based on the phenotypic detection of antibiotic resistance by measuring bacterial growth in the presence of the antibiotic being tested. These conventional methods take typically 24hours to obtain results. A review is presented here of recently developed techniques for the rapid determination of antibiotic susceptibility. Data obtained with different methods such as molecular techniques, flow cytometry, chemiluminescence, mass spectrometry, commercial methods used in routine work, colorimetric methods, nephelometry, microarrays, microfluids, and methods based on cell disruption and sequencing, are analyzed and discussed in detail.

[Use of MALDI-TOF in the rapid diagnosis of sepsis]. / Utilización de MALDI-TOF en el diagnóstico rápido de la sepsis.

The introduction of mass spectrometry through MALDI-TOF (matrix-assisted laser desorption ionization time-of-flight) in the diagnosis of bacteraemia and fungaemia has represented a revolution due to the rapidity and reliability of the results that it can offer to microbiology services and laboratories through analysis of the mass spectrum of the bacterial protein directly from positive blood culture bottles. These data are more useful if they are used in conjunction with other techniques able to identify the antibiotic resistance pattern of the microorganism. There is a need for a process of standardising sample processing protocols and for perfecting the identification of the agents causing bacteraemia, especially in some species of Gram-positive cocci and in polymicrobial processes. The introduction of this methodology provides rapid information that is highly important for the clinical management of bacteraemia. The availability of a multidisciplinary working group that applies all this information quickly and correctly in hospitals will improve the quality of care, reduce antibiotic expenditure and hospital stay and help to control the serious problem of antibiotic resistance.

[Molecular diagnostic methods of respiratory infections. Has the scheme diagnosis changed?]. / Métodos moleculares de diagnóstico de infecciones respiratorias. ¿Ha cambiado el esquema diagnóstico?

Lower respiratory tract infections remain one of the most common causes of mortality worldwide, which is why early diagnosis is crucial. Traditionally the microbiological diagnosis of these infections has been based on conventional methods including culture on artificial media for isolation of bacteria and fungi and cell cultures for virus and antibody or antigen detection using antigen-antibody reactions. The main drawback of the above mentioned methods is the time needed for an etiological diagnosis of the infection. The techniques based on molecular biology have drawn much attention in recent decades as tools for rapid diagnosis of infections. Some techniques are very expensive, especially those that can detect various microorganisms in the same reaction, therefore the question that arises is whether the cost of such testing is justified by the information obtained and by the clinical impact that its implementation will determine. In this article we make a review of the various techniques of molecular biology applied to the diagnosis of pneumonia and focus primarily on analysing the impact they may have on the management of patients with acute respiratory tract infections.

Diagnostic performance of rapid diagnostic tests for the diagnosis of malaria at public health facilities in north-west Ethiopia.

OBJECTIVE: To assess the performance of RDTs against nested polymerase chain reaction (nPCR) for the diagnosis of malaria in public health facilities in north-western Ethiopia. METHODS: Cross-sectional study at public health facilities in North Gondar, Ethiopia, of 359 febrile patients with signs and symptoms consistent with malaria. Finger prick blood samples were collected for testing in a P. falciparum/pan-malaria RDTs and for molecular analysis. Sensitivity, specificity and predictive values were determined for the RDTs using nPCR as reference diagnostic method. Kappa value was determined to demonstrate the consistency of the results between the diagnostic tools. RESULTS: By RDTs, 22.28% (80/359) of patients tested positive for malaria, and by nPCR, 27.02% (97/359) did. In nPCR, 1.67% (6/359) and 0.28% (1/359) samples were positive for P. ovale and P. malariae, which had almost all tested negative in the RDTs. The sensitivity, specificity, positive and negative predictive values of RDTs for the diagnosis of malaria were 62.9%, 92.7%, 76.3% and 87.1%, respectively, with 0.589 measurement agreement between RDTs and nPCR. The sensitivity and specificity of RDTs for P. falciparum identification only were 70.8% and 95.2%, and 65.2% and 93.1% for P. vivax. CONCLUSION: Although RDTs are commonly used at health posts in resource-limited environments, their sensitivity and specificity for the detection and species identification of Plasmodium parasites were poor compared to nPCR, suggesting caution in interpreting RDTs results. Particularly, in the light of expanded efforts to eliminate malaria in the country, more sensitive diagnostic procedures will be needed.

The diagnostic accuracy of three rapid diagnostic tests for typhoid fever at Chittagong Medical College Hospital, Chittagong, Bangladesh.

OBJECTIVE: To determine the diagnostic accuracy of three rapid diagnostic tests (RDTs) for typhoid fever in febrile hospitalised patients in Bangladesh. METHODS: Febrile adults and children admitted to Chittagong Medical College Hospital, Bangladesh, were investigated with Bact/Alert(®) blood cultures and real-time PCR to detect Salmonella enterica Typhi and Paratyphi A and assays for Rickettsia, leptospirosis and dengue fever. Acute serum samples were examined with the LifeAssay (LA) Test-it™ Typhoid IgM lateral flow assay detecting IgM antibodies against S. Typhi O antigen, CTKBiotech Onsite Typhoid IgG/IgM Combo Rapid-test cassette lateral flow assay detecting IgG and IgM antibodies against S. Typhi O and H antigens and SD Bioline line assay for IgG and IgM antibodies against S. Typhi proteins. RESULTS: In 300 malaria smear-negative febrile patients [median (IQR) age of 13.5 (5-31) years], 34 (11.3%) had confirmed typhoid fever: 19 positive by blood culture for S. Typhi (three blood PCR positive) and 15 blood culture negative but PCR positive for S. Typhi in blood. The respective sensitivity and specificity of the three RDTs in patients using a composite reference standard of blood culture and/or PCR-confirmed typhoid fever were 59% and 61% for LifeAssay, 59% and 74% for the CTK IgM and/or IgG, and 24% and 96% for the SD Bioline RDT IgM and/or IgG. The LifeAssay RDT had a sensitivity of 63% and a specificity of 91% when modified with a positive cut-off of ≥2+ and analysed using a Bayesian latent class model. CONCLUSIONS: These typhoid RDTs demonstrated moderate diagnostic accuracies, and better tests are needed.

[Rapid identification of microorganisms by mass spectrometry in a blood culture system. Comparison of two procedures]. / Identificación rápida de microorganismos de frascos de hemocultivos por espectrometría de masas. Comparación de 2 procedimientos diagnósticos.

Rapid identification of microorganisms is critical in hospitalized infected patients. Blood culture is currently the gold standard for detecting and identifying microorganisms causing bacteremia or sepsis. The introduction of mass spectrometry by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF MS) in microbiology laboratories, especially in microorganisms growing in blood culture bottles, provides rapid identification. This study evaluates the performance of the Maldi Sepsityper Biotyper procedure (hereinafter, MS) compared to that of an in-home method (hereinafter, HF). Eight hundred and forty (840) positive blood culture bottles were processed using the HF procedure, 542 of which were also processed using MS. The organisms were identified in 670 (79.76%) and 391 (72.14%) bottles respectively (p = 0,0013). This study demonstrates the effectiveness of both procedures for identifying microorganisms directly from positive blood culture bottles. However, the HF procedure proved to be more effective than MS, especially in the presence of Gram positive organisms.

Rapid diagnostic tests for dengue would reduce hospitalizations, healthcare costs and antibiotic prescriptions in Spain: A cost-effectiveness analysis.

BACKGROUND: Current gold standard diagnostic techniques for dengue are expensive and time-consuming. Rapid diagnostic tests (RDTs) have been proposed as alternatives, although data about their potential impact in non-endemic areas is scarce. METHODS: We performed a cost-effectiveness analysis comparing the costs of dengue RDTs to the current standard of care for the management of febrile returning travelers in Spain. Effectiveness was measured in terms of potential averted hospital admissions and reduction of empirical antibiotics, based on 2015-2020 dengue admissions at Hospital Clinic Barcelona (Spain). RESULTS: Dengue RDTs were associated with 53.6% (95% CI: 33.9-72.5) reduction of hospital admissions and were estimated to save 289.08-389.31€ per traveler tested. Moreover, RDTs would have avoided the use of antibiotics in 46.4% (95% CI: 27.5-66.1) of dengue patients. DISCUSSION: Implementation of dengue RDTs for the management of febrile travelers is a cost-saving strategy that would lead to a reduction of half of dengue admissions and a reduction of inappropriate antibiotics in Spain.

Evaluation of FebriDx® for the management of children with acute febrile respiratory infection.

INTRODUCTION: Acute respiratory infections (ARI) are a common cause of inappropriate antibiotic prescription (ATB) in pediatrics. FebriDx® is a rapid diagnostic test that differentiates between viral and bacterial infections. The objective is to analyse the impact of FebriDx® on ATB prescription when managing febrile ARI. METHODS: Prospective study carried out in patients aged 1-<18 years with febrile ARI in the emergency department. FebriDx® was performed and the impact on management was evaluated at follow-up. RESULTS: A total of 216 patients were included. Clinical assessment and FebriDx® result coincided coincided in 174 (80.5%) cases. A modification of the initial therapeutic plan was made in 22 (52.4%) of the 42 discordant ones (10.2% of the overall patients). In pneumonia the impact was 34.5%; in all cases it involved not prescribing ATB. CONCLUSIONS: FebriDx® could be a useful tool in the management of pediatric patients with febrile ARI to optimize ATB prescription.