Drug Supply Research Articles

Laying the foundations for high-quality mortality surveillance in Sierra Leone: Early learnings from the Child Health and Mortality Prevention Surveillance (CHAMPS) Network

Background More than four million child deaths occur annually; most are neither adequately documented nor investigated. The Child Health and Mortality Prevention Surveillance (CHAMPS) program was launched in Sierra Leone (SL) to generate high-quality data to determine definitive causes of stillbirths and under-five mortality (U5M) to inform decision-makers. Despite the multiple challenges of a greenfield research site, we highlight the experience of setting up a high-quality mortality surveillance (MS) system, including the viability of Minimal Invasive Tissue Sampling (MITS). Methods To establish the MS program, we implemented qualitative research and community entry, a sensitive system for timely identification and notification of deaths and followed CHAMPS standard operating procedures for investigating deaths and assigning accurate and definitive causes of death. CHAMPS in SL was implemented in four phases during 2017-2019 by a consortium. Enrolled stillbirths and U5M underwent verbal autopsy, clinical-data-abstractions, MITS, microbiology, molecular and histopathological diagnoses, and Determination of Cause of Death (DeCoDe). Results CHAMPS achieved a 93% consent rate, capitalizing on existing Ministry of Health infrastructure, community involvement, and local ownership. As of December 2022, 3,433 deaths were registered, with 1,056 (31%) eligible for enrolment. Of 439 cases DeCoDed, 402 (92%) of case-families had received feedback on the cause of death. Using findings and recommendations from the DeCoDe experts, CHAMPS is implementing interventions to reduce stillbirths and U5M at CHAMPS SL, including clinical review meetings, provision of emergency drugs and routine child death audits. Conclusion Implementing innovative MS in a challenging context, such as SL, is possible. Building on local knowledge and infrastructure has enabled the CHAMPS project to achieve remarkably high consent rates, given the cultural, religious and sensitivity challenges surrounding seeking consent for MITS from caregivers who have just lost a child. The programme has invested significantly in upscaling local technical capacity for surveillance and laboratory diagnostics.

Pricing dynamics of anti-seizure medications in the U.S.

BackgroundThe median cost of anti-seizure medications (ASM) in the United States (U.S.) nearly doubled per person between 2006 and 2021. This increase, combined with shifts in ASM usage and the impact of the COVID-19 pandemic on drug supply chains amid rising inflation, underscored the urgent need to scrutinize ASM pricing dynamics. This study aimed to analyze the complex dynamics of ASM pricing in the U.S. over the past decade (2013–2023); this included how the entry of generic ASMs influenced the pricing of brand-name counterparts and what impacted price variations across different ASM formulations (e.g., significant inflation, the COVID-19 pandemic). MethodsThis study utilized National Average Drug Acquisition Cost (NADAC) data from November 2013 to July 2023. We adjusted ASM prices for inflation using the Consumer Price Index for Medicinal Drugs - Seasonally Adjusted (CPI-MDS). Statistical analyses included fixed effects regressions and multivariable regression analysis to evaluate the impact of inflation, the number of medication labelers, and the COVID-19 pandemic on ASM prices. ResultsOur study analyzed 23 ASMs approved by the U.S. Food and Drug Administration (FDA), which encompassed 223 oral formulations:112 brand-name and 111 generics. From 2013–2016 to 2020–2023, accounting for standard deviations (SD), the average price of brand-name ASMs increased from $8.71 (SD 5.9) to $15.43 (SD 10.7), while generic ASMs saw a slight decrease from $1.39 (SD 1.8) to $1.26 (SD 1.6). Consequently, the price gap between brand-name and generic ASMs surged from 1452.39 % to 3399.26 %. The proportion of matched brand-name and generic ASMs with a price difference of 1000 %–9999 % increased from 32.88 % (2013–2016) to 41.43 % (2020–2023), while those exceeding 10,000 % rose from 16.44 % to 20 % in the same period. Generic immediate-release (IR) formulations were significantly less expensive than extended-release (ER) or delayed-release (DR) counterparts, with cost differences reaching up to 7751.20 %. The number of medication labelers was inversely related to generic ASM prices, which decreased by 5.45 % (p = 0.001) with each additional generic labeler, while brand-name ASM prices increased by 2.46 % (p < 0.001) with each additional generic labeler. The COVID-19 pandemic led to a 24.4 % increase in brand-name ASM prices and a 23.1 % decrease in generic ASM prices. ConclusionsThe findings reveal an expanding price disparity between brand-name and generic oral ASMs. An inverse relationship was observed between the number of medication labelers and generic ASM prices, with additional labelers driving down generic prices. However, introducing more generic labelers led to a significant increase in brand-name ASM prices. Furthermore, following patent expirations, brand-name ASM prices rose—a trend explained by the "generics paradox," where, contrary to expectations, brand prices do not decrease and may even increase when generics enter the market. These findings underscore the need for targeted interventions in drug pricing policies to manage the rising costs associated with epilepsy treatment. To ensure equitable access to ASMs, stakeholders must understand and address the factors driving these pricing dynamics.

Lived experiences of diabetes self-management among persons with disabilities in rural Tamil Nadu – a case study approach

BackgroundPeople with disabilities have numerous challenges in diabetes self-management. Poor self-management leads to the worsening of disability and secondary complications of diabetes. This study was conducted to explore the challenges in diabetes self-management and the factors influencing diabetes self-management among people with disabilities.MethodsWe conducted 16 case studies among people with physical, neurological, visual, hearing, and multiple disabilities who were affected by diabetes. We adopted a thematic content analysis approach to analyse the data.ResultsPeople with disabilities have challenges in adopting healthy diets as they are unable to purchase and consume fruits and vegetables which are costly, unavailable, and inaccessible. They have difficulty in doing physical activity due to lack of inclusive public spaces which are inaccessible, lack of motivation, and dependence on others for their mobility. Irregular drug supply in the public health system and unaffordable cost of drugs hamper adherence to medications. Laboratories are inaccessible to people with disabilities thus preventing monitoring of blood sugars. They have poor quality of life, life with pain and mental health issues, which prevent adoption of self-management behaviors. The intersectionality of age and gender with disability worsens self-management behaviors. Inaccessible health system, poor quality of health care and insensitive health care providers further complicate self-management.ConclusionThis study documents the challenges faced by persons with disabilities in practicing diabetes self management. There is a need for public health policy and planning that is inclusive of persons with disabilities to make access to diabetes care universal.

A Scoping Review of the Utilization of Opioid Use Treatment, Harm Reduction, and Culturally Tailored Interventions Among Racial/Ethnic Minorities in the United States

AbstractAs part of a multilayered scoping review, we assessed literature on prevention and management interventions for racial/ethnic minorities in the United States (US) who non-medically use prescription opioids and/or who use illicit opioids such as heroin. The review specifically focused on access to and uptake of medications for opioid use disorder (MOUD) and harm reduction resources. We conducted a scoping review of peer-reviewed literature and governmental reports published between January 2000 and August 2024 on patterns of access to, and acceptability and utilization of, overdose prevention and opioid use management resources among racial/ethnic minorities in the US. Searches were conducted on Cochrane, PubMed, Embase, and Google Scholar, with us examining studies on the uptake of MOUD, such as buprenorphine and methadone, syringe services programs (SSPs), safe consumption sites, and harm reduction resources like naloxone (used to reverse overdoses) and fentanyl test strips (used to test for the presence of fentanyl in drug supplies). Additionally, we sought to identify and describe existing interventions for opioid use prevention and management that have expressly incorporated cultural adaptations related to racial/ethnic minorities’ specific needs and preferences in an effort to improve participants' sense of salience and acceptability and thus enhance utilization. We further endeavored to leverage this scoping review towards the development of research and intervention guidelines contoured to improve future scholarship and programming with these populations. The existing evidence suggests that racial/ethnic minorities in the US, specifically Black individuals, have diminished access to and/or utilization of preventive and management resources and amenities such as buprenorphine and naloxone, owing to structural deficits, provider bias, socioeconomic obstacles, geographic barriers, and communal stigma and distrust. Black individuals, relative to White individuals, also appear less likely to report using SSPs to obtain syringes and related resources, but across racial groups, those who used SSPs were more likely to be trained in, possess, and/or use naloxone. Further, there have been very few culturally tailored interventions for harm reduction or MOUD; there were limited data across the reviewed works on Native American/Indigenous or Asian populations; and the broader body of literature lacks methodological rigor. We close by proposing a cultural humility-focused model for better meeting the complex needs of these populations through research and primary and secondary intervention.

Access and barriers to safer supply prescribing during a toxic drug emergency: a mixed methods study of implementation in British Columbia, Canada

BackgroundIn March 2020, British Columbia, Canada, introduced prescribed safer supply involving the distribution of pharmaceutical grade alternatives to the unregulated toxic drug supply. Prior research has demonstrated positive impacts on overdose mortality, but with limited reach to people who use substances. Objectives of this study were to (1) identify barriers to accessing safer supply prescribing among people who use substances; and (2) determine whether and how barriers differed between people with and without prescriptions, and between urban and rural settings.MethodsWe conducted a participatory mixed-methods study guided by the Consolidated Framework for Implementation Research. Participants (≥ 19 years old) had received a safer supply prescription or were seeking one (survey n = 353; interviews n = 54).ResultsParticipants who had a prescription were more likely to be living in a large urban centre, compared to medium/smaller centres and rural areas (78.5% vs. 65.8%, standardized mean difference = 0.286). Participants who did not have a prescription were more likely to report an array of structural, interpersonal, and health-related barriers (compared to those who had a prescription). In interviews, participants linked experiences of barriers to stigma and criminalization, low availability of services, lack of information and prescribers, not being able to get what they need, and anxieties, worries and doubts stemming from personal circumstances. There were no notable differences between large urban centres and medium/smaller centres and rural areas in the presence of specific types of barriers.ConclusionsFindings demonstrate restricted access to safer supply prescribing outside of large urban centres and provide future targets for enhancing implementation. Attention is needed to promote equity and counter systemic barriers in the implementation of responses to the ongoing toxic drug emergency.

Correlates of fentanyl preference among people who use drugs in Rhode Island

BackgroundFentanyl is increasingly pervasive in the unregulated drug supply and is a driver of drug overdose deaths in the United States. The aims of this study were to characterize and identify correlates of fentanyl preference among people who use drugs (PWUD) in Rhode Island (RI).MethodsUsing bivariate analysis, we examined associations between fentanyl preference and sociodemographic and psychosocial characteristics at baseline among participants enrolled in the RI Prescription Drug and Illicit Drug Study from August 2020-February 2023. Fentanyl preference was operationalized based on responses to a five-point Likert scale: “I prefer using fentanyl or drugs that have fentanyl in them.” Participants who responded that they “strongly disagree,” “disagree,” or were “neutral” with respect to this statement were classified as not preferring fentanyl, whereas participants who responded that they “agree” or “strongly agree” were classified as preferring fentanyl.ResultsAmong 506 PWUD eligible for inclusion in this analysis, 15% expressed a preference for fentanyl or drugs containing fentanyl as their drug of choice. In bivariate analyses, preference for fentanyl was positively associated with younger age, white race, lifetime history of overdose, history of injection drug use, past month enrollment in a substance use treatment program, past month treatment with medications for opioid use disorder, and preferences for heroin and crystal methamphetamine (all p < 0.05). Descriptive data yielded further insight into reasons for fentanyl preference, the predominant having to do with perceived effects of the drug and desire to avoid withdrawal symptoms.ConclusionsOnly a relatively small subset of study participants preferred drugs containing fentanyl. Given the increased prevalence of fentanyl contamination across substances within the unregulated drug market, the result for PWUD is increasingly less agency with respect to choice of drug; for example, people may be forced to use fentanyl due to restricted supply and the need to mitigate withdrawal symptoms, or may be using fentanyl without intending to do so. Novel and more effective interventions for PWUD, including increased access to age-appropriate harm reduction programs such as fentanyl test strips and overdose prevention centers, are needed to mitigate fentanyl-related harms.

A qualitative study on reasons for women’s loss and resumption of Option B plus care in Ethiopia

Loss to follow-up (LTFU) from Option B plus, a lifelong antiretroviral therapy (ART) for pregnant women living with human immunodeficiency virus (HIV), irrespective of their clinical stage and CD4 count, threatens the elimination of vertical transmission of the virus from mothers to their infants. However, evidence on reasons for LTFU and resumption after LTFU to Option B plus care among women has been limited in Ethiopia. Therefore, this study explored why women were LTFU from the service and what made them resume or refuse resumption after LTFU in Ethiopia. An exploratory, descriptive qualitative study using 46 in-depth interviews was employed among purposely selected women who were lost from Option B plus care or resumed care after LTFU, health care providers, and mother support group (MSG) members working in the prevention of mother-to-child transmission unit. A thematic analysis using an inductive approach was used to analyze the data and build subthemes and themes. Open Code Version 4.03 software assists in data management, from open coding to developing themes and sub-themes. We found that low socioeconomic status, poor relationship with husband and/or family, lack of support from partners, family members, or government, HIV-related stigma, and discrimination, lack of awareness on HIV treatment and perceived drug side effects, religious belief, shortage of drug supply, inadequate service access, and fear of confidentiality breach by healthcare workers were major reasons for LTFU. Healthcare workers' dedication to tracing lost women, partner encouragement, and feeling sick prompted women to resume care after LTFU. This study highlighted financial burdens, partner violence, and societal and health service-related factors discouraged compliance to retention among women in Option B plus care in Ethiopia. Women's empowerment and partner engagement were of vital importance to retain them in care and eliminate vertical transmission of the virus among infants born to HIV-positive women.

Who is culpable in fentanyl-induced deaths? A survey vignette investigating public perceptions of drug supplier culpability

PurposeThe fentanyl crisis has received national attention. In the current context, this study sought to assess whether public perception of criminal culpability varies by who supplies fentanyl to an individual who later dies from an overdose. MethodsAn experimental vignette of fentanyl-induced death scenarios was implemented by randomizing the relationship of the drug suppliers to the victims as well as race of both the drug supplier and victim. In total, there were eight scenarios. ResultsOLS regressions on a sample of 4820, found that respondents assigned a scenario where a drug dealer was the fentanyl provider (compared to a friend as the provider) were significantly more likely to support punitive action. There were no significant differences when the race of the drug provider and/or victim were randomized. Robustness checks confirmed these punitive attitudes towards drug dealers. ConclusionsThe public views drug dealers as more culpable in fentanyl overdoses. However, the race of both the drug supplier and victim did not impact perceptions of criminal culpability. During a national fentanyl epidemic, the findings have implications for public attitudes towards drug suppliers, public policy, and future research.

Drug supply management at first-level public health facilities: Case of Pyay District, Myanmar.

First-level public health facilities (PHFs) serve as primary providers of essential medicines, necessitating critical attention to drug availability and quality assurance. This study aimed to examine the status of functional areas within the drug supply chain management framework and assess the overall capability maturity at first-level PHFs. The cross-sectional study was conducted among 183 drug store sites from six townships of Pyay District. Only situational analysis was exercised to determine the existing situations. The overall capability maturity was determined according to the definitions of levels of the Capability Maturity Module Tool. 58.47% lacked formal drug supply management training, with 23.5% not undergoing performance reviews. Drug forecasting predominantly relied on a pen-paper system (91.6%) and factors like patient load (87.39%), drug consumption (85.71%), and disease prevalence (64.71%). Store site analysis revealed that 65.03% exhibited marginal capability, lacking standardized drugstores and employing unstandardized procedures. Storage practices varied, with 48.69% storing drugs conveniently and others categorizing them by drug type (32.79%) or using the first-expired-first-out system (40.98%). Approximately 42.69% reported having expired drugs. Concerning transportation costs, 37.16% incurred expenses exceeding 20,000 Kyats per time, with management staff often covering the costs. Waste management methods included burial pits (49.18%), incineration (62.84%), and sharp pits (55.19%). A majority (78.14%) used safety boxes, and 57.38% implemented a color-coded system for waste bins. The logistics management information system was entirely paper-based (100%). On average, assessments of drug quality conditions and physical damages scored 46.51% and 48.20%, respectively. The overall supply chain maturity at first-level public health facilities is at a marginal capability level (36.35%). While some basic drug supply chain management procedures were in place, they were not consistently followed, and many systems remain manual. The findings underscored significant inconsistencies in the management functions of supplied drugs, with poor adherence to Standard Operating Procedure guidelines.

Timely data on the dynamic drug supply is crucial in addressing the ongoing drug poisoning crisis. The team is exploring ways to share information with emergency responders, healthcare providers, government officials, and pwSUD.

ObjectiveTransitioning from hospitals to primary care brings significant challenges, including increased readmission rates, mortality, and costs due to information gaps. Alberta, Canada, addressed this by integrating 1000+ health systems and implementing Connect Care (CC), a Clinical Information System (CIS), to enhance patient safety and care coordination. In 2020, the Primary Health Care Integration Network (PHCIN) released the Home to Hospital to Home (H2H2H) Transitions Guideline and metrics to improve patient outcomes and system integration. ApproachThis study examines provincial data on H2H2H transitions measures from acute care hospitals using CC between April 1, 2022, and October 31, 2023, to assess transitions and support improvement efforts. CC data assesses transition components, including confirming primary care providers at hospital discharge, utilizing the LACE Readmission Risk Index, and ensuring timely discharge summary (DS) signoffs. It links with administrative data to evaluate post-discharge outcomes like primary care physician follow-up, unplanned readmissions, and Emergency Department (ED) visits. Results47 CC-implemented sites show nearly 80% discharges identified a primary care provider; less than 5% incorporated the LACE index in DS. About 90-93% of DS were signed within 24-72 hours. Approximately 62% of moderate-risk and 55% of high-risk discharges received timely follow-up. Readmission and ED visit rates within 7-30 days varied from 2-8% and 5-11% respectively. ConclusionIn conclusion, adopting CC and H2H2H transition metrics facilitates integrated care measurement, highlighting the need for risk index inclusion and high-risk discharge follow-up for improved patient transitions. Sustained initiatives are vital for optimal outcomes and system integration in Alberta.

Drug Shortages and Patient Harms

What Is the Issue? Drug shortages are a global issue with complex dynamics. Shortages can occur because of disruption at any point along the drug supply chain. Several strategies are used in Canada to prevent or alleviate the effects of drug shortages, including mandatory reporting by drug manufacturers. An understanding of the amount and types of real or potential harms caused to patients can inform policy decisions around drug shortage management and prevention. What Did We Do? We searched for literature providing evidence on patient outcomes associated with supply chain disruptions of pharmaceuticals and vaccines. An information specialist conducted a search of peer-reviewed literature sources published between January 1, 2003, and September 13, 2023. Documents were excluded if the objective was to investigate the potential effects of a drug shortage in the absence of an actual drug shortage or if the outcomes were not direct patient harms. What Did We Find? One scoping review and 33 nonrandomized studies were identified that evaluated patient outcomes associated with supply chain disruptions of pharmaceuticals and vaccines. We identified a wide variety of drug classes experiencing shortages. The most frequently reported shortages were anesthetics, oncology drugs, vaccines, drugs for the treatment of COVID-19, antimicrobials, and small-volume parenteral solutions. Most of the included primary studies concluded that the replacement drug or protocol was a safe or acceptable alternative to the shortage drug. The subset of primary studies that concluded that the replacement drug or protocol was not a safe or acceptable alternative to the shortage drug reported worse outcomes in health system use (including length of hospital stay), adverse events, disease progression, and mortality. What Does This Mean? Drug shortages have the potential to cause harm to patients and some drug shortages may have a greater impact on patients than others. The ability to predict which drugs could cause the greatest harm during a supply disruption would be a great benefit for future planning. The diversity of drugs experiencing shortages and their associated harms emphasizes that decision-makers may need to take a case-by-case approach when developing policies meant to lessen the impact of drug shortages.

Measures of stimulant medications: A population-based study in Alberta, Canada

ObjectivesStimulants are a class of drugs approved for the treatment of attention-deficit hyperactivity disorder (ADHD) and narcolepsy. However, they are also often used “off-label” as adjunct therapies for the treatment of obesity and depression. The objective of this study is to summarize how stimulant use is globally measured in the literature and to explore rates of stimulant use in Alberta, Canada. MethodsA traditional narrative literature review was conducted to summarize global methods of stimulant assessment. Then using definitions guided by the literature and current regulatory bodies in Alberta, we conducted a series of descriptive analyses to assess how frequent stimulant use was in Alberta patients from 2019 to 2021: 1) number of dispenses by year; 2) average days of drug supply; 3) proportion of days covered (PDC); and 4) defined daily dose (DDDs). ResultsIn the literature review, the most frequently used measures of stimulant drug use were trends over time (prevalence), types of drug use, and dispensations of prescriptions. In all, there is a global trend of increased use of stimulants among both adults and children. In Alberta, 173,789 patients were prescribed stimulant medication in 2019–2021, representing approximately 4 % of the entire Alberta population. Overall, 61.1 % were between the ages of 10–34 and 46.8 % were female. The number of dispensations rose from 713,896 in 2019 to 973,930 in 2021 – with up to 43 % being lisdexamfetamine stimulant dispenses. ConclusionsAlthough stimulant use in AB was measured using similar trend estimates as the literature, there is a lack of research to support whether these measures are accurate and effective at the population-level. Future steps to standardize both medical and nonmedical use of prescription stimulants are warranted in efforts to fully quantify both benefits and risks associated with stimulant use.

Effectiveness of malaria chemoprevention in the first two years of life in Cameroon and Côte d’Ivoire compared to standard of care: study protocol for a population-based prospective cohort impact evaluation study

BackgroundPerennial malaria chemoprevention (PMC) is a chemoprevention strategy endorsed by the World Health Organization (WHO) and is increasingly being adopted by National Malaria Programmes. PMC aims to reduce morbidity and mortality caused by malaria and anaemia in in young children through provision of antimalarial drugs at routine contact points with the local health system. This study aims to evaluate the impact of the programmatically-implemented country-tailored PMC programmes targeting children up to two years of age using sulfadoxine-pyrimethamine (SP) on the incidence of malaria and anaemia in children in Cameroon and Côte d’Ivoire.MethodsWe will assess the impact of PMC using passive and active monitoring of a prospective observational cohort of children up to 36 months of age at recruitment in selected study sites in Cameroon and Côte d’Ivoire. The primary and secondary outcomes include malaria, anaemia and malnutrition incidence. We will also conduct a time-series analysis of passively detected malaria and anaemia cases comparing the periods before and after PMC introduction. This study is powered to detect a 30% and 40% reduction of malaria incidence compared to the standard of care in Cameroon and Côte d’Ivoire, respectively.DiscussionThis multi-country study aims to provide evidence of the effectiveness of PMC targeting children in the first two years of life on malaria and anaemia and will provide important information to inform optimal operationalization and evaluation of this strategy.Trial RegistrationCameroon - NCT05889052; Côte d’Ivoire - NCT05856357.

The choice of optimal therapy for ER+ HER2-metastatic breast cancer (PROMETHEUS): all-Russian analysis of physicians’ preferences – updated survey results

Cyclin-dependent kinase 4/6 inhibitors (iCDK4/6) are the generally accepted standard of care for the treatment of luminal HER2-negative metastatic breast cancer (ER+HER2- mBC). Data from randomized and observational studies have proven the high effectiveness of the combination of iCDK4/6 and endocrine therapy (ET) both in the 1st and in subsequent lines. The use of new drugs in real clinical practice is determined by a number of factors, including the awareness of doctors, their personal experience and subjective preferences, as well as financial support and availability in a particular region. To assess the frequency of prescription of CDK4/6, as well as other types of treatment in the 1st‑2nd line of therapy for ER+ HER2- mBC in real clinical practice in Russia, as well as to determine the factors and preferences of doctors influencing their choice, the National Association of Oncomammologists (NAOM) conducted a survey “Prometheus” of oncology specialists. From February 15 to August 30, 2023, a web survey of healthcare professionals who treat patients with mBC was conducted on the website anketolog.ru. An invitation to survey was sent out through the NAOM database, 112 questionnaires were received and processed. Earlier, in 2020, the “Prometheus” survey was conducted on the territory of the Russian Federation for a similar purpose. In this paper, we present the results of an updated and expanded survey and evaluate changes that have occurred over the past 3 years in actual clinical practice. The results of a 2023 survey conducted in the Russian Federation on the choice of early-line therapy for ER+HER2- mBC showed that, compared with the 2020 survey, the level of “trust” in iCDK4/6 has increased among practicing physicians, and the indications for their use have expanded, including visceral metastases (and even pending visceral crisis), the indications for prescribing chemotherapy in the 1st line have narrowed. When using monoET in the 1st line, the majority of respondents prescribe iCDK4/6 in the 2nd line. Obviously, the wider use of iCDK4/6 is associated not only with the accumulation of clinical knowledge and experience in the use of drugs, but also with improved drug supply. However, the main limitations to the use of iCDK4/6 are still insufficient funding and organizational difficulties. However, it should be noted that 1/5 of the respondents do not face any restrictions and widely prescribe combination therapy.

Buprenorphine-Precipitated Withdrawal Among Hospitalized Patients Using Fentanyl

Buprenorphine treatment of opioid use disorder (OUD) is safe and effective, but opioid withdrawal during treatment initiation is associated with poor retention in care. As fentanyl has replaced heroin in the drug supply, case reports and surveys have indicated increased concern for buprenorphine-precipitated withdrawal (PW); however, some observational studies have found a low incidence of PW. To estimate buprenorphine PW incidence and assess factors associated with PW among emergency department (ED) or hospitalized patients. This retrospective cohort study at 3 academic hospitals in Philadelphia, Pennsylvania, included adults with OUD who underwent traditional or high-dose buprenorphine initiation between January 1, 2020, and December 31, 2021. Exclusion criteria included low-dose buprenorphine initiation and missing documentation of opioid withdrawal severity within 4 hours of receiving buprenorphine. Buprenorphine initiation with an initial dose of at least 2 mg of sublingual buprenorphine after a Clinical Opiate Withdrawal Scale (COWS) score of 8 or higher. Additional exposures included 4 predefined factors potentially associated with PW: severity of opioid withdrawal before buprenorphine (COWS score of 8-12 vs ≥13), initial buprenorphine dose (2 vs 4 or ≥8 mg), body mass index (BMI) (<25 vs 25 to <30 or ≥30; calculated as weight in kilograms divided by height in meters squared), and urine fentanyl concentration (0 to <20 vs 20 to <200 or ≥200 ng/mL). The main outcome was PW incidence, defined as a 5-point or greater increase in COWS score from immediately before to within 4 hours after buprenorphine initiation. Logistic regression was used to estimate the odds of PW associated with the 4 aforementioned predefined factors. The cohort included 226 patients (150 [66.4%] male; mean [SD] age, 38.6 [10.8] years). Overall, 26 patients (11.5%) met criteria for PW. Among patients with PW, median change in COWS score was 9 points (IQR, 6-13 points). Of 123 patients with confirmed fentanyl use, 20 (16.3%) had PW. In unadjusted and adjusted models, BMI of 30 or greater compared with less than 25 (adjusted odds ratio [AOR], 5.12; 95% CI, 1.31-19.92) and urine fentanyl concentration of 200 ng/mL or greater compared with less than 20 ng/mL (AOR, 8.37; 95% CI, 1.60-43.89) were associated with PW. In this retrospective cohort study, 11.5% of patients developed PW after buprenorphine initiation in ED or hospital settings. Future studies should confirm the rate of PW and assess whether bioaccumulated fentanyl is a risk factor for PW.

Impact of an Etoposide Chemotherapy Shortage on Patients With Extensive-Stage Small-Cell Lung Cancer: Results of a Natural Experiment.

A shortage of essential intravenous (IV) etoposide lasted from 2018 until 2020 in Ontario, Canada, allowing for a natural experiment in which external factors (IV etoposide availability) dictated patients' treatment assignment. The purpose of this study was to evaluate the impact of this IV etoposide shortage (IVES) on patient care outcomes. Individuals with extensive-stage small-cell lung cancer (ES-SCLC) treated during a pre-IVES (November 2017-October 2018) and IVES (November 2018-October 2019) time intervals were retrospectively reviewed at the Verspeeten Family Cancer Centre. We investigated the association of the shortage on health care utilization and survival using a time-to-event analysis, Cox proportional hazards and logistic regression modeling. A total of 119 patients with ES-SCLC were assessed, 49 in the pre-IVES interval and 70 in the IVES interval. The median age was 68 (IQR, 62-74) years, 48% (n = 57) were male, 33% (n = 39) had CNS metastases, and 69% (n = 82) received first-line systemic therapy. Alternate regimens used for IVES cohort included IV platinum-oral (PO) etoposide, IV platinum-IV irinotecan, and PO etoposide monotherapy. An adjusted multivariable model demonstrated a significant increase in hospitalization (odds ratio, 2.30 [95% CI, 1.01 to 5.24]; P = .047) and shorter progression-free survival (PFS; hazard ratio, 1.79 [95% CI, 1.19 to 2.68]; P = .005) during the IVES. This study demonstrated increased hospitalization, and decreased PFS, among patients with ES-SCLC treated with alternate chemotherapy regimens during an IVES. The impact of cancer drug shortages can be harmful, and optimizing a more secure drug supply with mitigation strategies is warranted.

Blockchain-Based Secured Drug Traceability in Health Care Application

Despite the enormous advancements in technology, fraudsters continue to attack the healthcare industry. Numerous recent healthcare security breaches indicate that attackers are focussing on the electronic health data and the drug supply chain. Additional investigation into security problems in the healthcare sector demonstrates that the primary cause of these incidents is the centralisation of data storage. The healthcare sector also lacks immutability, adaptability, security, and privacy in addition to having insufficient documentation. It has been discovered that blockchain technology may offer a complete solution to the main issues the healthcare industry is now facing. Healthcare issues may be resolved with the aid of blockchain's intrinsic qualities, which include immutability, transparency, privacy, security, and documentation. In this work, an interactive blockchain 2.0 medication supply chain tracking system is created, and Hyperledger Calliper is used to measure the system's performance. This system makes sure that everyone involved in the drug supply chain can follow the drug's journey from the producer to the end user. The members' own inventory management is also aided by it. In addition to providing privacy and transparency, this method offers a viable remedy for the issues associated with counterfeit drugs. With one ordered peer and one endorsed peer, the system can process 25,000 transactions per second.

Social complexity of a fentanyl vaccine to prevent opioid overdose conference proceedings: Radcliffe Institute for Advanced Study conference proceedings

Despite significant public health attention and investment, hundreds of thousands of individuals have suffered fatal opioid overdose since the onset of the opioid crisis. Risk of opioid overdose has been exacerbated by the influx of fentanyl, a powerful synthetic opioid, into the drug supply. The National Institutes of Health Helping End Addiction Long-term (HEAL) Initiative is supporting the development of vaccines targeting fentanyl to protect against overdose. If successful, a vaccine would induce anti-fentanyl antibodies to sequester fentanyl (but not other opioids) in the blood, preventing fentanyl from crossing into the brain and reaching the central nervous system where it can cause overdose. Introduction of an overdose preventing strategy that relies on a vaccine to confer passive protection may be impactful. However, vaccines are poorly understood by the public and politicized. Moreover, the overdose ecosystem is complex and extends across numerous social, economic, medical, and cultural systems. As such, optimal use of a vaccine strategy to address overdose may benefit from multidisciplinary consideration of the social, ethical, and systemic factors that influence substance use and overdose that may also impact the acceptability of a fentanyl vaccine and related implementation strategies.In March 2022, Dr. Elissa Weitzman convened a two-day conference at the Harvard Radcliffe Institute for Advanced Study on the Social Complexity of a Fentanyl Vaccine to Prevent Opioid Overdose. In all, 19 professionals from diverse disciplines (medicine, psychology, history, ethics, immunology, vaccinology, communications, policy) attended the conference and led discussions that centered on population health and epidemiology, history of medicine and frameworks for understanding substance use, ethics, decision-making and attitudes, and operational issues to the question of a novel immunotherapy targeting fentanyl overdose. Participants also debated the risks and benefits of vaccine administration in response to fictional clinical case vignettes. A summary of the conference presentations and discussions follows.

High concordance between urine toxicology results and self-reported fentanyl use in Nevada and New Mexico

Background Co-use of stimulants and opioids is often deliberate. However, the possibility remains that some people are unintentionally consuming fentanyl. To advance understanding of overdose risk, we examined the rate of concordance between self-reported fentanyl use and corresponding urine toxicology screen results. Methods Between August 2022–August 2023, 411 participants (adults who reported any non-medical drug use in the past three months) in Nevada and New Mexico completed a cross-sectional survey, of whom 64% (n = 270; the analytical sample) also completed a urine toxicology screen, which detects fentanyl use in the past three days. Positive predictive value, negative predictive value, sensitivity, and specificity were calculated using self-reported past three-day fentanyl use (yes/no) and urine toxicology screen results for the presence of fentanyl (positive/negative). Results Of the 270 participants who provided a urine sample, 268 are included in the descriptive statistics (two with inconclusive urine toxicology screen results were excluded). Of the 268 participants, 146 (54.5%) had a fentanyl-positive urine toxicology screen result, 122 (45.5%) had a fentanyl-negative urine toxicology screen result, 137 (51.1%) reported past three-day fentanyl use, and 130 (48.5%) reported no past three-day fentanyl use. Only 6.9% of those with a fentanyl-positive urine toxicology screen did not report recent fentanyl use. The sensitivity of self-reported fentanyl use was 93%, specificity was 97%, positive predictive value was 97%, and negative predictive value was 92%. Discussion The rate of unanticipated exposure to fentanyl (that is, positive urine screen and negative self-report) in this sample was low, at 6.9%. This runs counter to the national narrative that there is widespread unknown contamination of fentanyl in the drug supply. Conclusion Future research is needed to further explore how people who use multiple substances interpret their overdose risk and what harm reduction methods they employ.

How substance use preferences and practices relate to fentanyl exposure among people who use drugs in Rhode Island, USA

BackgroundOver 107,000 people died in the United States (U.S.) from drug overdose in 2022, with over one million overdose deaths since 1999. The U.S. drug market is characterized by a highly toxic, unregulated, and rapidly changing supply. Understanding the extent of exposure to fentanyl among people who use drugs (PWUD) will guide public health interventions aimed to decrease overdose. MethodsWe utilized baseline data from the Rhode Island Prescription and Illicit Drug Study, a randomized controlled trial of harm reduction-oriented interventions for PWUD in Rhode Island from 2020 to 2023. We evaluated sociodemographic and drug use-related covariates and examined fentanyl presence in urine drug testing (UDT). We built a classification and regression tree (CART) model to identify subpopulations with the highest likelihood of fentanyl presence in UDT. ResultsAmong 446 participants, those with fentanyl present in UDT tended to be younger, non-Hispanic white, and had recently injected drugs (p<0.05 for all). The CART analysis demonstrated a large variation in sample sub-groups’ likelihood of fentanyl presence in UDT, from an estimated probability of 0.09 to 0.90. Expected recent fentanyl exposure was the most important predictor of fentanyl in UDT. ConclusionsUnivariate analyses and CART modeling showed substantial variation in the presence of fentanyl in UDT among PWUD. Harm reduction services for people actively injecting drugs and drug checking programs based on capacity-building, empowerment, and targeted towards those not yet engaged in services are urgently needed to support PWUD in navigating the current volatile drug supply.