BACKGROUND: The overdose crisis driven by synthetic opioids continues to escalate in the USA. We evaluated the efficacy of multiple manufacturing lots of a fentanyl test strip (FTS) to detect fentanyl and fentanyl analogs and assessed cross-reactivity with possible interferences. METHODS: Drug standards were dissolved in water in a laboratory setting and serially diluted. Drug dilutions were tested using five different manufacturing lots of BTNX Rapid Response (20 ng/mL cutoff) lateral flow chromatographic immunoassay strips to assess lot-to-lot variability for FTS sensitivity and cross-reactivity for the analytes of interest. RESULTS: All five manufacturing lots cross-reacted with fentanyl and eleven fentanyl analogs. Diphenhydramine, lidocaine, MDMA, and methamphetamine were found to cause false positives with the strips. There was notable lot-to-lot variability in the sensitivity of the strips for fentanyl, fentanyl analogs, and known interferences. DISCUSSION: FTS remains an important overdose prevention tool, but lot-to-lot variability in performance complicates robust instructions that balance the prevention of false positives and false negatives. Continued lot-to-lot performance assessment is recommended to ensure health education for FTS remains accurate. More sophisticated drug checking technologies and services are needed in the community landscape to augment personal FTS use to facilitate informed consumption and overdose risk mitigation.

BACKGROUND: Liquid chromatography-high-resolution mass spectrometry (LC-HR-MS) has emerged as a powerful analytical technology for compound screening in clinical toxicology. To evaluate the potential of LC-HR-MS3 in detecting toxic natural products, a spectral library of 85 natural products (79 alkaloids) that contains both MS2 and MS3 mass spectra was constructed and used to identify the natural products. Samples were analyzed using an LC-HR-MS3 method and the generated data were matched to the spectral library to identify the natural products. METHODS: To test the performance of the LC-HR-MS3 method in different sample matrices, the 85 natural product standards were divided into three groups to separate structural isomers and avoid ion suppression effects caused by co-elution of multiple analytes. The grouped analytes were spiked into drug-free serum and drug-free urine to produce contrived clinical samples. RESULTS: The compound identification results of the 85 natural products in urine and serum samples were obtained. The match scores using both MS2 and MS3 mass spectra and those using only MS2 mass spectra were compared at 10 different analyte concentrations. The two types of data analysis provided identical identification results for the majority of the analytes (96% in serum, 92% in urine), whereas, for the remaining analytes, the MS2-MS3 tree data analysis had better performance in identifying them at lower concentrations. CONCLUSION: This study shows that in comparison to LC-HR-MS (MS2), LC-HR-MS3 can increase the performance in identification of a small group of the toxic natural products tested in serum and urine specimens.

Objective

Determine the COVID-19 seroconversion rate for patients with multiple myeloma receiving a COVID-19 vaccine.

Materials and methods

After 45 patients received their second COVID-19 vaccine dose, their serum IgG antibodies were measured: 22 with monoclonal gammopathy (MG) of unknown significance, 3 with smoldering myeloma, 2 with light chain amyloidosis, and 18 with MG (9 in remission, 6 out of remission, and 3 with free light-chain gammopathy alone). A second serum specimen was retained for 16 patients with MG. Their antibody levels were compared to those of 78 uninfected healthy vaccinated control patients.

Results

Three patients with MG had low antibody levels on blood collected 98, 100, and 113 days after the initial vaccine dose (2 with MG of unknown significance and 1 with hypogammaglobulemia). The other 40 patients with MG (seroconversion rate 93%) and both patients with amyloidosis produced antibodies. Relative to days after vaccination, patients with MG had lower antibody levels than control patients.

Conclusion

After receiving a COVID-19 vaccine, most patients with MG produce anti-SARS-CoV-2 antibodies comparable to levels in uninfected vaccinated healthy control patients.

Background

Numerous reports have led to concerns that fentanyl is added to many street drugs as an adulterant, including to stimulants like cocaine and methamphetamine, and could increase risks for negative health outcomes.

Methods

We collected information regarding recent substance use through self-report and urine toxicology (confirmed with mass spectrometry) once a month for up to 6 monthly study visits from a probability sample of 245 women in San Francisco with a history of housing instability (2016-2019). We compared the presence of fentanyl metabolites with (1) the presence of metabolites for other substances and (2) self-reported past week substance use.

Results

Out of 1050 study visits, fentanyl metabolites were detected 35 times (i.e., at 3% of all study visits and among 19/245, or 8% of all women). In most but not all (91%, or 32/35) of these detected cases, heroin or opioid medication use was self-reported. Among women who reported cocaine or methamphetamine use, but did not use heroin or opioid medication, fentanyl was detected in only 1 of 349 cases (0.3%). In adjusted logistic regression, the presence of fentanyl metabolites was independently associated with (1) presence of opiate, heroin, and benzodiazepine metabolites, and (2) self-reported past week use of heroin and opioid medications. Fentanyl metabolite detection was not independently associated with cocaine or methamphetamine use.

Conclusions

The presence of fentanyl metabolites in this population was almost entirely among women who also reported using heroin or opioid pills. These data do not support the hypothesis that fentanyl is being routinely added to stimulants as an adulterant on a large scale in this region.

Background

Concomitant use of opioids and promethazine has been reported in various subpopulations, including methadone maintenance patients, injection drug users, and at-risk teenagers. Promethazine is thought to potentiate the "high" from opioids. However, to date, the prevalence of promethazine use has not been determined among patients prescribed opioids for chronic pain.

Methods

Urine samples from 921 patients prescribed opioids for chronic pain were analyzed for promethazine. Demographic data, toxicology results, and opioid prescription information were obtained through medical record abstraction. We assessed the prevalence and factors associated with promethazine use with bivariable and multivariable statistics.

Results

The prevalence of promethazine-positive urine samples among chronic pain patients was 9%. Only 50% of promethazine-positive patients had an active prescription for promethazine. Having benzodiazepine-positive urine with no prescription for a benzodiazepine was statistically associated with promethazine use. Also, having a prescription for methadone for pain or being in methadone maintenance for the treatment of opioid dependence were both statistically associated with promethazine use. Chronic pain patients prescribed only a long-acting opioid were more likely to have promethazine-positive urines than patients prescribed a short-acting opioid.

Conclusions

The study provides compelling evidence of significant promethazine use in chronic pain patients. Promethazine should be considered as a potential drug of abuse that could cause increased morbidity in opioid-using populations.

Introduction

Viral infections have been implicated in the initiation of the autoimmune diseases. Recent reports suggest that a proportion of patients with COVID-19 develop severe disease with multiple organ injuries. We evaluated the relationship between COVID-19 severity, prevalence and persistence of antinuclear and other systemic and organ specific autoantibodies as well as SARS-CoV-2 infection specific anti-nucleocapsid (N) IgG antibodies and protective neutralizing antibody (Nab) levels.

Methods

Samples from 119 COVID-19 patients categorized based on their level of care and 284 healthy subjects were tested for the presence and persistence of antinuclear and other systemic and organ specific autoantibodies as well as SARS-CoV-2 and neutralizing antibody levels.

Results

The data shows significantly increased levels of anti RNP-A, anti-nucleocapsid and neutralizing antibody among patients receiving ICU care compared to non-ICU care. Furthermore, subjects receiving ICU care demonstrated significantly higher nucleocapsid IgG levels among the RNP-A positive cohort compared to RNP-A negative cohort. Notably, the expression of anti RNP-A antibodies is transient that reverts to non-reactive status between 20 and 60 days post symptom onset.

Conclusions

COVID-19 patients in ICU care exhibit significantly higher levels of transient RNP-A autoantibodies, anti-nucleocapsid, and SARS-CoV-2 neutralizing antibodies compared to patients in non-ICU care.

Background

The SARS-CoV-2 virus has mutated and evolved since the inception of the COVID-19 pandemic bringing into question the future effectiveness of current vaccines and antibody therapeutics. With evolution of the virus updated methods for the evaluation of the immune response in infected and vaccinated individuals are required to determine the durability of the immune response to SARS-CoV-2 variants.

Methods

We developed a multiplexed surrogate virus neutralization test (plex-sVNT) that simultaneously measures the ability of antibodies in serum to inhibit binding between angiotensin converting enzyme-2 (ACE2) and 7 SARS-CoV-2 trimeric spike protein variants, including wild type, B.1.1.7(α), B.1.351(β), P.1(γ), B.1.617.2(δ), B.1.617.1(κ), and B.1.429(ε). The assay was validated against a plaque reduction neutralization test (PRNT).We evaluated 170 samples from 97 COVID-19 patients and 281 samples from 188 individuals that received the Pfizer-BioNTech or Moderna mRNA vaccines.

Results

The plex-sVNT demonstrated >96% concordance with PRNT. Antibody neutralization activity was significantly reduced for all SARS-CoV-2 variants compared to wild type in both the infected and vaccinated cohorts. There was a decline in overall antibody neutralization activity, within both cohorts, out to 5 months post infection or vaccination, with the rate of decline being more significant for the vaccinated.

Conclusions

The plex-sVNT provides a correlative measure to PRNT and a convenient approach for evaluating antibody neutralization against SARS-CoV-2 variants. Neutralization of SARS-CoV-2 variants is reduced compared to wild type and declines over the ensuing months after exposure or vaccination within each cohort, however it is still unknown what degree of neutralizing capacity is protective.

Background

Cocaine is a well-known risk factor for acute cardiac events, but the effects in users outside of acute events are less clear. We investigated a possible association between cocaine use and the concentration of a novel biomarker for cardiac stress and heart failure, ST2.

Methods

A case-control study was conducted to compare ST2 concentrations by the presence of cocaine in patients presenting for care, but not cardiac care, at an urban safety net hospital.

Results

In samples taken from 100 cocaine-positive and 100 cocaine-negative patients, the presence of cocaine was associated with ST2 concentrations>35ng/mL. Serum concentrations of benzoylecgonine, a major cocaine metabolite, were significantly correlated with ST2 concentrations.

Conclusions

Cocaine use is associated with subclinical cardiac stress and damage outside of acute cardiac events. This information could add to better stratification of cocaine users with elevated ST2 concentrations who may be at higher risk for developing heart failure and other cardiac complications.