High-risk Drug Research Articles

EN-452411-5 THE ELECTROPHYSIOLOGIC EFFECTS OF KCNQ1 EXTEND BEYOND EXPRESSION OF IKS: EVIDENCE FROM GENETIC AND PHARMACOLOGIC BLOCK

Co-expression of KCNQ1 and KCNE1 generates the repolarizing current IKs. While mutations in KCNQ1 are the commonest cause of the congenital long QT syndrome, we and others find only a small IKs in normal cardiomyocytes from human induced pluripotent stem cells (iPSC-CMs) or human ventricular myocytes. A role for IKs expression as a modulator of the other major delayed rectifier in the heart, IKr, has previously been suggested. We used pharmacologic and genetic approaches to probe the role of IKs in human cardiac repolarization. We studied population control iPSC-CMs and iPSC-CMs from a patient with Jervell and Lange-Nielsen (JLN) syndrome due to compound heterozygous loss of function KCNQ1 variants. We compared the effects of pharmacologic IKs block with HMR-1556 to those of genetic KCNQ1 ablation, using JLN cells, cells homozygous for the KCNQ1 loss of function allele G643S, or siRNAs reducing KCNQ1 expression. We also studied the effects of two IKr blockers in the setting of pharmacologic and genetic ablation of KCNQ1: moxifloxacin, associated with a very low risk of drug-induced long QT, and dofetilide, a high-risk drug. In population cells, a small IKs was readily recorded but pharmacologic IKs block (by high-dose HMR-1556) produced no change in action potential duration at 90% repolarization (APD). By contrast, in cells with genetic ablation of KCNQ1 expression, APD was prolonged 77%. JLN cells displayed increased sensitivity to acute IKr block: the concentration of moxifloxacin required to prolong APD 100 msec (μM) was 237.4 (median, IQR 100.6-391.6, n=7) in population cells versus 22.4 (16.2-27.9, n=8) in JLN cells. In population control cells, chronic moxifloxacin exposure (300μM) mildly prolonged APD (10%), and unexpectedly increased IKs, while chronic exposure to dofetilide (5 nM) produced greater prolongation (58%) and no increase in IKs. In cells with genetic suppression of KCNQ1 expression, moxifloxacin did not increase IKs, and markedly prolonged APD. Our data strongly suggest that KCNQ1 expression modulates baseline cardiac repolarization, and the response to IKr block, through mechanisms beyond simply generating IKs.

ENHANCING PATIENT SAFETYA PRESCRIPTION AUDIT IN A TERTIARY CARE HOSPITAL

Prescription audits are an important aspect of patient safety practice. Medication errors are a common occurrence and need constant monitoring and audit for ensuring right medicine to right patient ,at right time with right dose and right administration and documentation. Medication error is any preventable event that may cause or lead to inappropriate medication use or patient harm in process of prescribing, order communication, product labelling, packaging, and nomenclature, compounding, dispensing, distribution, administration, education, monitoring, and use Objective- To audit the IPD prescriptions of the different wards and critical care areas for quality improvement in medication management A retrospective random sampling of 506 IPD les of June 2022 -July 2022 including Methodology- sample from wards and .ICU were included and team of trained auditors audited them according to a predened checklist . The ndings were subject to analysis and reports generated The 23 point checklist based audit nding Results- s revealed good compliance in documentation of the various audit points. Improvement was needed in capital letters use and writing of date and time along with authentication details .More detailed audits and in depth analysis is needed for further improvement The Conclusionaudit showed good compliance in documentation. There is need for focus audits for high risk drugs and doses of high alert medicines along side this audit

Rhabdomyolysis Caused by a Behavioral Manifestation of Acute Mania

AbstractIntroductionWhile seen in patients with bipolar disorder due to NMS, antipsychotic side effects, or substance use, rhabdomyolysis resulting from behaviors seen in mania has not been reported in recent literature. We present a case of a patient with rhabdomyolysis due to exertion during a manic episode.CaseA 29-year-old male with a history of bipolar disorder type 1 was brought to the ED in June 2022 after he was found on the roof of a local theater sharing excerpts from a book he had written. Temperatures outside were 100–102 Fahrenheit. On presentation, the patient had rapid, pressured speech and demonstrated flight of ideas. He was religiously preoccupied. He had been previously admitted to Psychiatric Emergency Services in April 2022 for mania and was discharged with lithium and lamotrigine. He had been titrating these medications with his outpatient psychiatrist.The patient’s labs showed an elevated creatinine of 1.49, up from his baseline of 1.09. Further workup revealed an elevated CK of 3,538. Additional abnormalities included an AST of 70, calcium of 10.6, total bilirubin of 1.6, and WBC of 15.5. He was afebrile, oriented, and had no obvious signs of infection. The patient received 2 liters of Lactated Ringers (LR) and was admitted to Internal Medicine. Later, he was agitated overnight and received 10mg olanzapine and 2mg lorazepam. Lithium level following fluid resuscitation was 0.6.On interview the next day, the patient described working on a creative religious piece that he wanted to share with others, leading to him climbing on the roof. He had been hyper-focused on this work, with 1–4 hours of sleep nightly. He also had been frequently doing gymnastics, walking long distances, and climbing other buildings. He endorsed diffuse muscle pain, but this was not reproducible on exam.150mL/hr of LR was started, and PO fluid intake was encouraged. He agreed to resume his medications and was started on lithium 900mg and lamotrigine 50mg. His CK continued to downtrend. WBC count decreased and was 12.9 at discharge. Lamotrigine was titrated up to home dose of 100mg. His mania improved, and he was ultimately discharged home with outpatient follow-up.ConclusionRhabdomyolysis results from the release of toxic cellular compounds from muscle fibers. Complications include acute renal failure, hyperkalemia, and compartment syndrome. Causes include substance use, medications, trauma, seizures, ischemia, overexertion, and dehydration. Recently reported cases of mania-associated rhabdomyolysis involve iatrogenic causes, such as neuromuscular malignant syndrome (NMS) and non-NMS antipsychotic side effects.Other causes include high-risk drug use during mania. Rhabdomyolysis due to behavioral manifestations of mania have been documented more rarely in older reports, similarly, addressing excessive exercise and dehydration. Therefore, our case represents a reminder of the medical sequalae resulting from actions undertaken during acute mania. This highlights the importance of implementing effective treatment to prevent such episodes.FundingNo Funding

Mothering and desistance from high-risk drug use amongst women in Malta: an evolved grounded theory study

PurposeThe purpose of this study is to explore and theorise about the desistance process of Maltese mothers who previously used drugs. The study unpacks how initial and continued desistance from high-risk drug use (HRDU) is impacted by being a mother within the Maltese context and identifies contingencies for desistance and examines how they are negotiated along the desistance pathways.Design/methodology/approachThe study adopted a symbolic interactionist-inspired career framework and involved in-depth exploration of trajectories of mothering and desistance of eight Maltese women with a history of HRDU. Data were gathered through in-depth interviews and analysis used an evolved grounded theory methodology.FindingsFour explanatory categories were identified in the interview data to document the role of mothering in the various pathways to desistance recounted by the women. These are: becoming a mother; differing pathways of desistance in relation to mothering; the lived experience; identity negotiation and transformation. This study highlights how identity fluidity and transformation is central to the desistance process.Practical implicationsThe paper aims to inform policy and practice with mothers who use drugs and their families and has important implications for the development and delivery of gender transformative interventions.Originality/valueThis study challenges taken-for-granted beliefs about the influence of mothering on desistance and identifies the complexities involved.

PrEP and HIV prevention decision-making among social network members of women who have experienced incarceration: a qualitative study

ABSTRACT Incarceration and HIV are a syndemic for US women, yet very few women who have experienced incarceration use pre-exposure prophylaxis (PrEP) for HIV. We conducted semi-structured interviews with 32 participants recruited by women who have experienced incarceration from their social networks, informed by the modified social ecological model for PrEP. Emergent themes from the interviews included individual-level (low personal HIV risk assessment, personal responsibility for HIV prevention, and decisions in addiction versus recovery), network-level (influential sex partners and the importance of trust, supportive treatment peers, and high-risk but indifferent drug use networks), community-level (stigma, and mitigation of stigma in supportive substance use disorder treatment environments), and public policy-level (incarceration and PrEP cost and access) determinants. PrEP interventions for women who have experienced incarceration and their networks will need to incorporate contingency planning into HIV risk assessment, navigate complex network dynamics, and be situated in trusted contexts to address structural barriers.

Synthetic cannabinoids awareness among patients with opioid use disorder in Serbia - A survey based cross-sectional pilot study.

There is limited data on the awareness and use of synthetic cannabinoids (SCs) in high-risk population in Serbia, despite SCs becoming more and more common at illicit drug market. This pilot study aimed to examine the awareness and prevalence of use of SCs in patients with an opioid-use disorder and to identify patient characteristics and other factors associated with SCs use. This cross-sectional study was conducted at the Clinic for Psychiatry, Clinical Center Vojvodina, Serbia, the largest tertiary health care institution in this region of the country. All patients hospitalized due to the treatment of opioid dependence during November and December 2017 were included (response rate 100%), and filled-out an anonymous questionnaire specifically developed for the purpose of this study. Differences between patients reporting SCs use and those who did not were compared using chi-square test with values of p < 0.05 were considered significant. Out of 64 patients (median age 36.37 years), one third (32.81%) reported using SCs. Socio-demographic characteristics of the subjects were not associated with SCs use. There were differences in the most common sources of information reported between the SCs users and non-users. Majority of SCs users (76.0%) were informed about SCs through friends, compared with just 26.0% of non-users (<0.001). Nearly all study participants (93.8%) were daily tobacco users. The share of respondents reporting alcohol and marihuana use was significantly higher among the SCs users (52.0% vs. 20.9%, p = 0.011 and 15.6% vs. 12.5%, p = 0.015), respectively. Higher share of SCs users used multiple psychoactive substances (38.1% vs. 16.3%), and this difference was statistically significant (p = 0.047). The most commonly reported adverse effect of SCs among users included dry mouth (81.0%), trouble thinking clearly (52.4%) and panic attacks (52.4%). Understanding the awareness and use of SCs among high-risk drug users, as well as associated factors can help improve substance-use disorder treatment in our setting. Educational activities targeting public are urgently needed to raise awareness on SCs, considering that social contacts are the main sources of information on SC for this vulnerable population. Users of SCs have also reported using other psychoactive substances more often, and this calls for a holistic approach addressing multiple factors to improve substance-use treatment in our setting.

Team Approach: Use of Opioids in Orthopaedic Practice.

The opioid epidemic represents a serious health burden on patients across the United States. This epidemic is particularly pertinent to the field of orthopaedics because it is one of the fields providing the highest volume of opioid prescriptions. The use of opioids before orthopaedic surgery has been associated with decreased patient-reported outcomes, increased surgery-related complications, and chronic opioid use. Several patient-level factors, such as preoperative opioid consumption and musculoskeletal and mental health conditions, contribute to the prolonged use of opioids after surgery, and various screening tools for identifying high-risk drug use patterns are available. The identification of these high-risk patients should be followed by strategies aimed at mitigating opioid misuse, including patient education, opioid use optimization, and a collaborative approach between health care providers.

The impact of training chemotherapy safety standards with a smartphone application on the knowledge, attitude, and performance of nurses

BackgroundNurses who play the leading role in caring for patients, especially nurses in the chemotherapy department who are constantly exposed to high-risk drugs and their side effects, should pay more attention to occupational safety. This study was performed to determine the effect of training chemotherapy safety standards using a smartphone application on nurses’ knowledge, attitude, and performance.MethodsThe whole enumeration of fifty oncology nurses was recruited who they worked in 3 hospitals affiliated with Lorestan University of Medical Sciences (west of Iran). The study was conducted from June to November 2021. The training was done for four weeks with a smartphone application, including six main courses of familiarity with hazardous drugs, Personal Protective Equipment, preparation, storage and transfer, spilling, and wastes disposal of hazardous drudges . The nurses’ knowledge, attitude, and performance questionnaire were completed before, immediately after, and one month after the intervention. Data analysis was performed using SPSS version 26, descriptive and inferential statistical tests of independent t-test, one-way analysis of variance, Spearman’s rank correlation coefficient, repeated measures analysis of variance, and the Generalized Estimating Equation (GEE) model.ResultsMean knowledge score of participants before, immediately after, and one month after the intervention was (47.18 ± 8.19), (60.08 ± 3.82), and (61.88 ± 3.45), respectively. The mean attitude score of participants before, immediately after, and one month after the intervention was (30.34 ± 3.94), (34.32 ± 3.25), and (34.98 ± 2.88), in order, and the mean performance score of participants before, immediately after, and one month after the intervention was (43.60 ± 5.11), (51.78 ± 3.15) and (52.88 ± 3.06), respectively. The mean nurses’ knowledge, attitude, and performance score increased significantly over time (P < 0.001).ConclusionsTeaching chemotherapy safety standards using the application improved oncology nurses’ knowledge, attitude, and performance. Appropriate educational programs, especially by new methods such as E-learning, are recommended for providing safety for nurses.

Prediction of Prednisolone Dose Correction Using Machine Learning

Wrong dose, a common prescription error, can cause serious patient harm, especially in the case of high-risk drugs like oral corticosteroids. This study aims to build a machine learning model to predict dose-related prescription modifications for oral prednisolone tablets (i.e., highly imbalanced data with very few positive cases). Prescription data were obtained from the electronic medical records at a single institute. Cluster analysis classified the clinical departments into six clusters with similar patterns of prednisolone prescription. Two patterns of training datasets were created with/without preprocessing by the SMOTE method. Five ML models (SVM, KNN, GB, RF, and BRF) and logistic regression (LR) models were constructed by Python. The model was internally validated by five-fold stratified cross-validation and was validated with a 30% holdout test dataset. Eighty-two thousand five hundred fifty-three prescribing data for prednisolone tablets containing 135 dose-corrected positive cases were obtained. In the original dataset (without SMOTE), only the BRF model showed a good performance (in test dataset, ROC-AUC:0.917, recall: 0.951). In the training dataset preprocessed by SMOTE, performance was improved on all models. The highest performance models with SMOTE were SVM (in test dataset, ROC-AUC: 0.820, recall: 0.659) and BRF (ROC-AUC: 0.814, recall: 0.634). Although the prescribing data for dose-related collection are highly imbalanced, various techniques such as the following have allowed us to build high-performance prediction models: data preprocessing by SMOTE, stratified cross-validation, and BRF classifier corresponding to imbalanced data. ML is useful in complicated dose audits such as oral prednisolone.

Drug reactions with eosinophilia and systemic symptoms induced by immune checkpoint inhibitors: an international cohort of 13 cases.

Among dermatologic adverse events induced by immune checkpoint inhibitors (ICI), drug reactions with eosinophilia and systemic symptoms (DRESS) have been very rarely reported. The objective of this study is to better define the clinical and histologic features, treatment and prognosis of ICI-related DRESS. This retrospective case series was conducted between 01 January 2015 and 31 December 2021 by the dermatology departments of five international networks involved in drug reactions. Inclusion criteria were age ≥18 years old, DRESS with Regiscar score ≥4 (probable or certain) and ICI as a suspect drug. Clinical, biologic and follow-up data were extracted from the medical charts. Thirteen patients were included. The median time to onset was 22 days (3-11). No patients had a high-risk drug introduced in the past 3 months. A majority of patients presented fever (92%), diffuse exanthema (77%) and facial edema (69%). Biologic features included hypereosinophilia in eight patients (61.5%), hyperlymphocytosis in 3 (23%), elevated liver function tests in 11 (85%, grade 1 or 2 in most cases) and renal involvement in 5 (38%). Two patients (15%) had lung involvement. PCR evidence of viral replication was detected in five patients (38.5%). Treatment involved discontinuation of the suspect ICI and systemic steroids with variable dose and duration regimens. Among the four patients in which ipilimumab + nivolumab combination therapy was initially suspected, one was rechallenged with nivolumab monotherapy with good tolerance. Five patients were switched to another anti-PD-1 plus low-dose systemic steroids, with good tolerance in four cases. No patient died because of DRESS. DRESS induced by ICI are rare and of moderate severity. A consensus for management is still pending.

Does acute kidney injury alerting improve patient outcomes?

BackgroundElectronic alerts (e-alerts) for Acute Kidney Injury (AKI) have been implemented into a variety of different Electronic Health Records (EHR) systems worldwide in order to improve recognition and encourage early appropriate management of AKI. We were interested in the impact on patient safety, specialist referral and clinical management.MethodsAll patients admitted to our institution with AKI were included in the study. We studied AKI progression, dialysis dependency, length of hospital stay, emergency readmission, ICU readmission, and death, before and after the introduction of electronic alerts. The impact on prescription of high risk drugs, fluid administration, and referral to renal services was also analysed.ResultsAfter the introduction of the e-alert, progression to higher AKI stage, emergency readmission to hospital and death during admission were significantly reduced. More prescriptions were stopped for drugs that adversely affect renal function in AKI and there was a significant increase in the ICU admissions and in the number of patients having dialysis, especially in earlier stages. Longer term mortality, renal referrals, and fluid alteration did not change significantly after the AKI e-alert introduction.ConclusionsAKI e-alerts can improve clinical outcomes in hospitalised patients.

Screening Incarcerated Women for Opioid Use Disorder.

The overall aim of the present study is to examine the utility of the DSM OUD Checklist and the NM-ASSIST screening tools to identify symptoms consistent with OUD among incarcerated women in county jails. This study contributes to the existing literature because research on screening and assessment approaches for incarcerated women has been limited. The focus of the current study is to describe the screening procedures and study recruitment for a larger parent study focused on increasing treatment linkages. Study findings indicate a positive correlation between indicators of OUD using the two screening tools, as well as a high degree of correlation between street opioid misuse and other high-risk drug indicators (overdose and injection practices). These findings underscore the importance of outreach, screening, and intervention in real-world settings, including jails, in order to increase access to OUD treatment among this vulnerable sample of women.

Genes related to N6-methyladenosine in the diagnosis and prognosis of idiopathic pulmonary fibrosis.

Introduction: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive pulmonary fibrotic disease with unknown etiology and poor outcomes. It severely affects the quality of life. In this study, we comprehensively analyzed the expression of N6-methyladenosine (m6A) RNA methylation regulators using gene expression data from various tissue sources in IPF patients and healthy volunteers. Methods: The gene expression matrix and clinical characteristics of IPF patients were retrieved from the Gene Expression Omnibus database. A random forest model was used to construct diagnosis signature m6A regulators. Regression analysis and correlation analysis were used to identify prognosis m6A regulators. Consensus cluster analysis was used to construct different m6A prognosis risk groups, then functional enrichment, immune infiltration and drug sensitivity analysis were performed. Result: Five candidate m6A genes from lung tissue were used to predict the incidence, and the incidence was validated using datasets from bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cells. Subsequently, the BALF dataset containing outcomes data was used for the prognosis analysis of m6A regulators. METTL14, G3BP2, and ZC3H13 were independent protective factors. Using correlation analysis with lung function in the lung tissue-derived dataset, METTL14 was a protective factor in IPF. Based on METTL14 and G3BP2, a consensus cluster analysis was applied to distinguish the prognostic m6A regulation patterns. The low-risk group's prognosis was significantly better than the high-risk group. Biological processes regulated by various risk groups included fibrogenesis and cell adhesion. Analysis of immune cell infiltration showed upregulation of neutrophils in the m6A high-risk group. Subsequently, five m6A high-risk group sensitive drugs and one m6A low-risk group sensitive drug were identified. Discussion: These findings suggest that m6A regulators are involved in the diagnosis and prognosis of IPF, and m6A patterns are a method to identify IPF outcomes.

Artículo traducido] Prevalencia de reacciones adversas a medicamentos asociadas a visitas al servicio de urgencias y factores de riesgo de hospitalización

ObjectiveAdverse drug reactions increase morbidity and mortality, prolong hospital stay and increase healthcare costs. The primary objective of this study was to determine the prevalence of emergency department visits for adverse drug reactions and to describe their characteristics. The secondary objective was to determine the predictor variables of hospitalization for adverse drug reactions associated with emergency department visits. MethodsObservational and retrospective study of adverse drug reactions registered in an emergency department, carried out from November 15th to December 15th, 2021. The demographic and clinical characteristics of the patients, the drugs involved and the adverse drug reactions were described. Logistic regression was performed to identify factors related to hospitalization for adverse drug reactions. Results10,799 patients visited the ED and 216 (2%) patients with adverse drug reactions were included. The mean age was 70 ± 17.5 (18-98) years and 47.7% of the patients were male. A total of 54.6% of patients required hospitalization and 1.6% died from adverse drug reactions. The total number of drugs involved was 315 with 149 different drugs. The pharmacological group corresponding to the nervous system constituted the most representative group (n = 81). High-risk medications, such as antithrombotic agents (n = 53), were the subgroup of medications that caused the most emergency department visits and hospitalization. Acenocumarol (n = 20) was the main drug involved. Gastrointestinal (n = 62) disorders were the most common. Diarrhea (n = 16) was the most frequent adverse drug reaction, while gastrointestinal bleeding (n = 13) caused the highest number of hospitalizations. Charlson comorbidity index behaved as an independent risk factor for hospitalization (aOR 3.24; 95% CI: 1.47-7.13; p=0.003, in Charlson comorbidity index 4-6, and aOR 20.07; 95% CI: 6.87–58.64; p = 0.000, in Charlson comorbidity index ≥ 10). ConclusionsThe prevalence of emergency department visits for adverse drug reactions continues to be a non-negligible health problem. High-risk drugs such as antithrombotic agents were the main therapeutic subgroup involved. Charlson comorbidity index was an independent factor in hospitalization, while gastrointestinal bleeding was the adverse drug reaction with the highest number of hospital admissions.

A deep learning platform to assess drug proarrhythmia risk.

Drug safety initiatives have endorsed human iPSC-derived cardiomyocytes (hiPSC-CMs) as an invitro model for predicting drug-induced cardiac arrhythmia. However, the extent to which human-defined features of invitro arrhythmia predict actual clinical risk has been much debated. Here, we trained a convolutional neural network classifier (CNN) to learn features of invitro action potential recordings of hiPSC-CMs that are associated with lethal Torsade de Pointes arrhythmia. The CNN classifier accurately predicted the risk of drug-induced arrhythmia in people. The risk profile of the test drugs was similar across hiPSC-CMs derived from different healthy donors. In contrast, pathogenic mutations that cause arrhythmogenic cardiomyopathies in patients significantly increased the proarrhythmic propensity to certain intermediate and high-risk drugs in the hiPSC-CMs. Thus, deep learning can identify invitro arrhythmic features that correlate with clinical arrhythmia and discern the influence of patient genetics on the risk of drug-induced arrhythmia.

Prevalence of adverse drug reactions associated with emergency department visits and risk factors for hospitalization

ObjectiveAdverse drug reactions increase morbidity and mortality, prolong hospital stay and increase healthcare costs. The primary objective of this study was to determine the prevalence of emergency department visits for adverse drug reactions and to describe their characteristics. The secondary objective was to determine the predictor variables of hospitalization for adverse drug reactions associated with emergency department visits. MethodsObservational and retrospective study of adverse drug reactions registered in an emergency department, carried out from November 15th to December 15th, 2021. The demographic and clinical characteristics of the patients, the drugs involved and the adverse drug reactions were described. Logistic regression was performed to identify factors related to hospitalization for adverse drug reactions. Results10,799 patients visited the emergency department and 216 (2%) patients with adverse drug reactions were included. The mean age was 70 ± 17.5 (18-98) years and 47.7% of the patients were male. A total of 54.6% of patients required hospitalization and 1.6% died from adverse drug reactions. The total number of drugs involved was 315 with 149 different drugs. The pharmacological group corresponding to the nervous system constituted the most representative group (n = 81). High-risk medications, such as antithrombotic agents (n = 53), were the subgroup of medications that caused the most emergency department visits and hospitalization. Acenocumarol (n = 20) was the main drug involved. Gastrointestinal (n = 62) disorders were the most common. Diarrhea (n = 16) was the most frequent adverse drug reaction, while gastrointestinal bleeding (n = 13) caused the highest number of hospitalizations. Charlson comorbidity index behaved as an independent risk factor for hospitalization (aOR 3.24, 95% CI: 1.47–7.13, p = 0.003, in Charlson comorbidity index 4–6; and aOR 20.07, 95% CI: 6.87–58.64, p = 0.000, in Charlson comorbidity index ≥ 10). ConclusionsThe prevalence of emergency department visits for adverse drug reactions continues to be a non-negligible health problem. High-risk drugs such as antithrombotic agents were the main therapeutic subgroup involved. Charlson comorbidity index was an independent factor in hospitalization, while gastrointestinal bleeding was the adverse drug reaction with the highest number of hospital admissions.

Sexualized Substance Use among Female Sex Workers in Iran: Findings from a Nationwide Survey

Background: Female sex workers (FSWs) are at higher risk of HIV due to high-risk sexual and drug use related behaviors. This study characterized sexualized substance use among FSWs in Iran. Methods: In 2015, 1,337 FSWs were recruited from centers for vulnerable women and through outreach efforts in 13 major cities in Iran. Data were collected via face-to-face interviews from consenting FSWs on a range of socio-demographic and behavioral characteristics. The primary outcome of interest was sexualized substance use, defined as reporting alcohol or drug use before or during sex in the past month. Bivariable and multivariable modified Poisson regression models were used to assess the correlates of sexualized substance use. Adjusted prevalence ratio (aPR) and 95% confidence interval (CI) were reported. Results: The prevalence of sexualized substance use was 31.3% (95% CI: 28.7, 34.0). Inconsistent condom use during sex with clients in the past month (aPR = 1.31; 95% CI: 1.01, 1.71), regular (i.e., at least weekly in the past month) alcohol use (aPR = 2.87; 95% CI: 2.17, 3.80), regular opioid use (aPR = 2.09; 95% CI: 1.45, 3.02), regular stimulant use (aPR = 2.68; 95% CI: 2.12, 3.39), and self-reported HIV negative status (aPR= 1.88; 95% CI: 1.14, 3.10) were significantly and positively associated with sexualized substance use. Conclusions: Sexualized substance use was associated with riskier sexual behavior and self-reported HIV sero-negativity. Harm reduction messaging to FSWs needs to go beyond focusing on sexual health promotion and further highlight the risks associated with sexualized substance use.

2061. High Rates of Viremic HIV, Risky Sexual Behaviors, and Interest in Gender Affirming Hormone Therapy among Transgender Individuals Who Engage in Transactional Sex

Abstract Background In the U.S., HIV transmission persists largely through sexual transmission in gender and sexual minorities. Transactional sex (TS) is a known risk factor for HIV transmission, yet risk behaviors and engagement in HIV treatment and other medical services among transgender (TG) individuals who have TS are poorly understood. Methods PATCH is a natural history study of TG individuals in Washington, DC. Participants complete laboratory testing and surveys, including assessment of TS – defined as previous year sex in exchange for drugs, money or shelter. Fisher’s exact test was used for statistical analysis. Results Of 54 participants assigned male at birth (AMAB), 21(39%) endorsed TS, the majority of whom were female (81%), Black (95%), median age 35, and HIV+ (76%; Table 1). Of those with HIV, 12 (75%) were prescribed ART, though only 8 (50%) had HIV VL &amp;lt; 200. The majority of TG people with TS had sex weekly or more (75%), with &amp;gt; 5 partners/year (62%) and used their penis (80%) and anus (90%) during TS. A minority consistently used condoms in receptive anal sex (29%), penetrative anal sex (25%), penetrative vaginal sex (17%), and chem sex (8%). While 95% had ever taken gender affirming hormone therapy (GAHT), 62% were not prescribed GAHT at screening, of whom, 54% were interested in seeing a provider for GAHT. When compared to non-TS participants, TG individuals with TS were more likely to have chem sex (p&amp;lt; 0.01), use drugs daily or more (p=0.04), use amphetamines (p&amp;lt; 0.01) and cocaine (p&amp;lt; 0.01), and less likely to have GAHT prescribed by a provider (p=0.03). HIV+ patients with TS were less likely to have HIV VL&amp;lt; 200 (p=0.02). Table 1:Participant Characteristics and Associations with Transactional Sex Conclusion This cohort of AMAB TG individuals with TS had high rates of viremic HIV, and multiple risk factors for HIV transmission, including frequent condomless sex with multiple partners. Additionally, those with TS were more likely to have high risk drug use, indicating that novel strategies to decrease risk associated with chem sex, particularly stimulant use, should be prioritized. Further, nearly all TG participants with TS had taken GAHT, yet were less likely to get GAHT from a provider. As many had interest in seeing a provider for GAHT, co-locating GAHT with HIV treatment and prevention services could help providers engage this population and address HIV-related risks. Disclosures Shyam Kottilil, MD, PhD, Arbutus Pharmaceuticals: Grant/Research Support|Gilead: Grant/Research Support|Merck: Grant/Research Support|Regeneron Pharmaceuticals: Advisor/Consultant|Silverback Therapeutics: Advisor/Consultant|The Liver Company: Advisor/Consultant|Yufan Biotechnologies: Advisor/Consultant Sarah Kattakuzhy, MD, Gilead: Grant/Research Support Elana S. Rosenthal, MD, Gilead: Grant/Research Support|Merck: Grant/Research Support.

Drug use and re-imprisonment: A prospective study of the Norwegian Offender Mental Health and Addiction (NorMA) cohort

BackgroundRe-imprisonments are common among people in prison who use drugs. This study aims to describe sociodemographic factors, mental health and level of pre-prison substance use in a cohort of people in prison, and to investigate re-imprisonment during follow-up according to their level of pre-prison drug use. MethodsThis was a prospective study using baseline data from the Norwegian Offender Mental Health and Addiction (NorMA) cohort (n = 733) recruited in 2013–2014 linked to data from the Norwegian Prison Registry and the Norwegian Cause of Death Registry. Self-reported drug use before imprisonment was measured at baseline using the Drug Use Disorder Identification Test (DUDIT). The outcome of interest was re-imprisonment examined using Cox regression. We excluded 32 persons because they were not released before the study ended. The study sample included 701 persons, with a total time-at-risk of 2479 person-years. ResultsAlmost half of the study sample reported high-risk drug use before imprisonment (DUDIT score >24). During the study period, 43% (n = 267) were re-imprisoned. People with high-risk use had a hazard ratio (HR) of 4.20 (95% CI: 2.95–5.97) of re-imprisonment compared with people with low-risk use (DUDIT score <6). Older age and more education than primary school were associated with a reduced risk of re-imprisonment. ConclusionCompared with low-risk use, high-risk drug use is highly prevalent among people in prison and is associated with higher rates of re-imprisonment. This highlights the need for screening and treatment of drug use disorders among people in prisons.

Clozapine therapeutic drug monitoring – experience from a large London NHS trust

Abstract Introduction Clozapine is a high-risk drug that is used widely in Secondary and Tertiary Centres.1 Therapeutic Drug Monitoring (TDM) advice and recommendation is readily available from distinguished authors.2,3 The rate of clozapine TDM, appropriate sample collection for TDM, appropriate actions following a clozapine level varies between services and prescribers within our organisation. Aim To establish how many current West London NHS Trust (WLT) patients had a clozapine TDM, how many plasma samples collected for TDM were done appropriately, the proportion of patients with an appropriately collected plasma sample result within the largely accepted therapeutic range, and whether there was documentation that the plasma level was reviewed and if any prescription changes were made. Methods Approval to undertake the service evaluation was given by the Trust clinical governance and audit committee as ethical review as not required. No patient identifiable details were shared or collected. All patients who had been registered on the Trusts clozapine patient monitoring service for over 8 weeks were enrolled. Anonymised patient demographic data was collected including concomitant medication. Plasma levels were sought for every patient enrolled. The appropriateness of the samples taken were scrutinised. The plasma level result was collected. Electronic patient notes were also scrutinised to assess actions following the plasma level result. Data were collected in a binary yes/no format and results calculated as a percentage. Data was stored and collected in accordance to Trust General Data Protection Regulation (GDPR). Results In total 316 patients were included. 97% of these patients had evidence of TDM levels done during the time of the audit. 88% of these patients’ samples were done correctly. Only 45% of patients had levels within the widely acceptable therapeutic range. Of those patients whose levels fell outside the therapeutic range less than half (42%) had documentation that the level was reviewed. Discussion/Conclusion It is widely accepted that clozapine TDM when done accurately can be a vital source of information to inform prescribers on the appropriate dose, concordance and toxicity of clozapine therapy. Our Trust showed evidence of routine clozapine TDM. There was some variation in the appropriate sample collection but what was most alarming is the lack of documentation that action was taken when the TDM level was outside the general acceptable range. Standardising the actions following clozapine TDM needs to be a priority for the Trust if clozapine TDM is to continue to be carried out in almost 100% of the patient population.