Can "oral fluid" be used instead of "urine" for rapid screening of drug of abuse: a prospective pilot study

Transcription

1 Hong Kong Journal of Emergency Medicine Can "oral fluid" be used instead of "urine" for rapid screening of drug of abuse: a prospective pilot study ATY Chow, VCH Ng, FL Lau Introduction: Spot urine tests are commonly employed by emergency physicians in Hong Kong to detect recent abusive drug exposure. Spot tests utilising oral fluid are gaining its popularity in other parts of the world. There was lack of evidence about employment of rapid oral fluid test () in the local emergency medical settings. The objective of this study is to determine the operating characteristics of, and to compare its agreement with the bedside urine immunoassay test (BUIT). Setting: The emergency department and the substance abuse clinic of a regional hospital. Methods: This was a single-centered cross-sectional study of diagnostic test. Patients suspected to have drug abuse were tested using either one or both of the commercially available and BUIT. The sensitivity, specificity and accuracy of both tests were calculated with reference to the laboratory urine toxicology screening results. The agreement between and BUIT was calculated. Results: For the detection of ketamine and methamphetamine (the two most prevalent abusive substances), had % sensitivity and % specificity, which were comparable to that of BUIT (74-100% sensitivity and 100% specificity). The overall observed agreement of and BUIT results was at least 96%. There was good agreement between and BUIT with kappa values of Conclusion: In this pilot study, the operating characteristics of are comparable with that of BUIT, with both tests showing good agreements in the detection of ketamine and methamphetamine uses. can potentially be employed as an alternative investigation for rapid diagnosis of patients with suspected drug abuse. (Hong Kong j.emerg.med. 2015;22: ) BUIT BUIT BUIT % % BUIT % 100% BUIT 96% BUIT BUIT Keywords: Bedside testings, diagnosis, drug abuse testing, substance abuse detection, saliva Correspondence to: Chow Tin Yat, Anthony, MBBS United Christian Hospital, Hong Kong Poison Information Centre, K3A, 130 Hip Wo Street, Kwun Tong, Kowloon, Hong Kong anthony666@gmail.com Ng Chun Ho, Vember, FHKAM(Emergency Medicine), Dip Clin Tox(HKPIC & HKCEM) Lau Fei Lung, FRCS(Edin), FHKAM(Emergency Medicine)

2 266 Hong Kong j. emerg. med. Vol. 22(5) Sep 2015 Introduction In Hong Kong, urine sample for laboratory analysis remains the major medium for detection of abusive drug exposure. Bedside urine immunoassay test (BUIT) (e.g. ACON, ABON, etc) are commonly used clinically as rapid means for evaluating patients suspected to have recent drug abuse. Compared with urine test, oral fluid testing had lower refusal rates and was generally more acceptable to the respondents. 1 Also, oral fluid is less likely to be adulterated or substituted, and more easily collected compared with urine samples. 2,3 Currently, there is no data concerning the accuracy of rapid oral fluid test () in the local population. Furthermore, is not commonly employed in other parts of the world to detect ketamine abuse. This pilot study serves as the first study worldwide to investigate such usage. The objective of this study was to evaluate the operating characteristics and diagnostic performance of in detecting different abusive substances in Hong Kong, in particular ketamine. Moreover, results were used to compare with that of BUIT, and their agreement would be determined. Materials and methods This study was a cross-sectional diagnostic study carried out in a single centre from 1st April 2014 to 31st January Patients at least 18 years old with suspected substance abuse, attending the Accident and Emergency Department (AED) or the AED substance abuse clinic of the United Christian Hospital, were recruited by convenient sampling. Exclusion criteria were patients less than 18 years old, unable to give consent, pregnant women, and those with no urine for laboratory toxicology screening saved (which served as the reference standard). This study was approved by the Hospital Authority Clinical Research Ethics Committee. Procedure After obtaining written consent, oral fluid was collected from patients and were performed, with the results recorded by an investigator. Urine sample was also collected for BUIT and was sent to the cluster laboratory for abusive drug screening using Liquid Chromatography Mass Spectrometry (LCMS) by independent trained personnel. Recent and past drug abusive history would then be collected using a standardised form. The kits used were subject to availability and supplied by the police. Data collection included demographics (sex, age), reported type of abusive drugs, date and time, amount, and route of administration of last abusive drugs used, date and time of oral fluid and urine collection, and urinalysis results, and patient's past drug abusive history. kits Two kits, named Securetec DrugWipe 5 S (kit 1), manufactured by Securetec Detektions-System AG in Neubiberg of Germany, and SalivaScreen DOA Oral-Fluid 008AS601 (kit 2), manufactured by ulti med Products (Deutschland) GmbH in Ahrensburg of Germany, were used in this study. The BUIT used were ABON Multi-Drug One Step Multi-Line Screen Test Device (Urine) REF DOA-1105 and ABON KET One Step Ketamine Test Device (Urine) REF DKE-102, manufactured by ABON Biopharm (Hangzhou) Co., Ltd in Hangzhou of China. The sample collector of Securetec DrugWipe 5 S consists of 3 small sampling pads, and oral fluid is collected by wiping this sample collector to the saliva from the tongue or the oral mucosa. A positive result is indicated by the presence of a red test line. The Securetec DrugWipe 5 S in this study can detect four abusive drugs: Cannabis, Amphetamine/ Methamphetamines, Ketamine and Cocaine. The sample collector of SalivaScreen DOA Oral-Fluid consists of a collector swab. The oral fluid is collected by sweeping the swab inside the mouth for several times, until the colour on the saturation indicator strip appears in the indicator window. A positive result is indicated by the absence of test line. The SalivaScreen DOA Oral-Fluid in this study can detect six different types of abusive drugs: Cocaine, Ketamine, Marijuana, Methamphetamine, 3,4-methylenedioxy-methamphetamine (MDMA) and 6-monoacetylmorphine (6-MAM).

3 Chow et al./rapid oral fluid test () study 267 Statistical analysis Data were reported as means or median with corresponding standard deviations or interquartile range (IQR). Categorical variables were expressed as proportions and percentages. The sensitivities, specificities, positive and negative likelihood ratios were calculated with reference standard of the laboratory urine assay by spectrometry. Agreements between different diagnostic tests were expressed as observed agreement percentage and by the Kappa statistic. All statistical calculations were performed using R Results In this study, 46 patients were recruited during the study period. One of them failed to provide urine for laboratory toxicology screening and was excluded from the study. The remaining 45 patients were included in the analysis, with 29 male (64%) and a median age of 31 years (IQR 29-38). The number of carried out and the number of invalid test results is shown in Table 1. All patients had BUIT carried out. The prevalence of ketamine, methamphetamine, opioid, cocaine, cannabis and MDMA abuse was 42.2%, 33.3%, 15.7%, 4.4%, 2.2% and 2.2% respectively. The operating characteristics of BUIT, kit 1 and kit 2 in detecting ketamine and methamphetamine, the two most prevalent abusive substances used locally, are summarised in Table 2. The agreement of with BUIT results are shown in Table 3. Comparing the results of with BUIT, the overall percentage agreement ranged from %, while the kappa values ranged from , indicating a very good agreement between them. Discussion This study served as the first local study to determine the performance of in the detection of recent use of abusive drugs in AED. It was also the first reported study in the literature to investigate its usage in ketamine abuse detection. In order to calculate the accuracy of different, the corresponding drug concentration in that oral fluid sample should ideally be used as the 'gold standard'. However, practically, the laboratory tests on drug concentration in oral fluid sample are not available in medical practices in Hong Kong. Urine for laboratory toxicology screening obtained by LCMS is commonly used as alternative to screen for recent abusive drugs exposure, and was therefore being used as a reference standard in this study. LCMS for drug screening is highly sensitive and specific, 4 and thus considered a suitable reference standard. Despite limited by a small sample size, this study showed a very good agreement between and BUIT, with kappa value at least also had comparable sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ration (NLR) and Table 1. Number of kit 1 and 2 carried out and number of invalid results No. of No. of No. of No. of No. of No. of tests done invalid tests successful tests (%) tests done invalid tests successful tests (%) Kit 1 Kit 2 Ket (100%) (83%) Met (100%) (93%) Coc (100%) (83%) THC (100%) (83%) Mor (80%) MDMA (83%) Ket: Ketamine; Met: Methamphetamine; Coc: Cocaine; THC: Cannabis; Mor: Opioid; MDMA: 3,4-methylenedioxy-methamphetamine *Invalid test: Test in which no control test line appeared.

4 268 Hong Kong j. emerg. med. Vol. 22(5) Sep 2015 accuracy with that of BUIT in detecting ketamine and methamphetamine abuse. Further study with targeted patients for the specific substances and larger sample size are required in order to determine its use in the detection of cocaine, cannabis, opioid and MDMA, etc. for ketamine had a good specificity 93-96% but a moderate sensitivity 72-79% in our study. The sensitivity calculated for ketamine was substantially lower than that of the other commonly abused drugs as shown in previous study. 5-7 This was not only limited to but was also observed for BUIT. One reason to account for this was the presence of spectrum bias for ketamine which was absence for the other drugs, as this study also recruited subjects from AED substance abuse clinic whose patients mainly consist of chronic ketamine abusers who were not in acute intoxication state. As a result of this, a majority of the false negative results (4 out of 5 for kit 2 and BUIT, and 3 out of 4 for kit 1) arose from subjects from the clinic. Further study including solely acutely intoxicated ketamine abuser from AED should provide results with higher sensitivity and better accuracy. Limitations The number of cases enrolled is inadequate for sensitivity calculation in this study. The estimated sample size required for adequate sensitivity and specificity for ketamine detection should be 177 and 39 respectively, using a method as described previously by Buderer, 8 assuming 90% sensitivity, 97% specificity (averaged from a previous study of other abusive Table 2. Operating characteristics of BUIT & (kit 1 & 2) for ketamine and methamphetamine Sensitivity (95% CI) Specificity (95% CI) PLR (95% CI) NLR (95% CI) Accuracy (95% CI) Ketamine BUIT 74% (49-91%) 100% (81-100%) * 0.26 ( ) 89% (76-96%) Kit 1 79% (54-94%) 96% (80-100%) 21 (3-142) 0.22 ( ) 89% (76-96%) Kit 2 72% (47-90%) 93% (68-100%) 11 (2-74) 0.30 ( ) 82% (65-93%) Methamphetamine BUIT 100% (70-100%) 100% (83-100%) * % (88-100%) Kit 1 87% (60-98%) 100% (83-100%) * 0.13 ( ) 96% (85-99%) Kit 2 100% (62-100%) 100% (81-100%) * % (86-100%) PLR: Positive likelihood ratio; NLR: Negative likelihood ratio *Since the specificity is 100%, PLR = sensitivity / (1-specificity) = (infinity) Table 3. Measures of agreement (percentage agreement and Kappa agreement) between with BUIT in detection of ketamine and methamphetamine P pos P neg P overall Kappa value (95%CI) Ketamine Kit 1 vs BUIT 94% 94% 96% 0.90 ( ) Kit 2 vs BUIT 97% 95% 97% 0.94 ( ) Kit 1 vs Kit 2 90% 92% 91% 0.82 ( ) Methamphetamine Kit 1 vs BUIT 93% 100% 96% 0.90 ( ) Kit 2 vs BUIT 100% 100% 100% 1.00 Kit 1 vs Kit 2 95% 98% 97% 0.93 ( ) P pos : Positive agreement; P neg : Negative agreement; P overall : Overall agreement

5 Chow et al./rapid oral fluid test () study 269 substances 7 ), the maximum marginal error of estimate not exceeding 7% with 95% confidence interval, and a 40% prevalence, according to the Narcotics Division of Hong Kong Our study served as a pilot study for provide insights to the diagnostic characteristics of for ketamine and methamphetamine in the local situation. It is not possible to get prior consent for the use of while the patient is in acute intoxication. By the time when consent was obtained, one's drug level might have already dropped to a level that was too low for the and BUIT to show positive result, but still be detectable by the laboratory LCMS method. Therefore, the number of false negative results was bound to be high in this study, and the sensitivity would be underestimated. Ideally, to prevent observer bias, results should be read by independent investigators blinded to the study. However, as the results of are either presence or absence of coloured band which is quite objective, blinding procedure was not done. Moreover, as the urine toxicology results were not yet available at the time of reading the results, observer bias should be limited. Nevertheless, having both tests read by the investigator in sequence may have introduced potential interpretation bias, which is one of the drawback of the study. Conclusion In this pilot study, for detecting ketamine and methamphetamine uses provided comparable results with BUIT. Further study with larger sample size is required to determine the potential for to be used as an alternatives investigation for rapid diagnosis of patients with suspected drug abuse. Acknowledgements The authors are grateful to Ms W Cheung for data entry and collection. All kits were supplied by the Hong Kong Police Force. References 1. Fendrich M, Johnson TP, Wislar JS, Hubbell A. Drug test feasibility in a general population household survey. Drug Alcohol Depend 2004;73(3): Cone EJ. Saliva testing for drugs of abuse. Ann NY Acad Sci 1993;694: Cone EJ. Legal, workplace, and treatment drug testing with alternate biological matrices on a global scale. Forensic Sci Int 2001;121(1-2): Maurer HH. Current role of liquid chromatographymass spectrometry in clinical and forensic toxicology. Anal Bioanal Chem 2007;388(7): Yacoubian GS Jr, Wish ED, Pérez DM. A comparison of saliva testing to urinalysis in an arrestee population. J Psychoactive Drugs 2001;33(3): Cone EJ, Huestis MA. Interpretation of oral fluid tests for drugs of abuse. Ann N Y Acad Sci 2007;1098: Yacoubian GS Jr, Cone EJ. A comparison between the Intercept Oral Fluid Collection Device and urinalysis among Balitmore City probationers. J Crim Just 2006; 34: Buderer NM. Statistical methodology: I. Incorporating the prevalence of disease into the sample size calculation for sensitivity and specificity. Acad Emerg Med 1996;3 (9):