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Despite a high vaccination rate, the COVID‐19 pandemic continues with immune‐evading Omicron variants. The success of additional antigenic stimulation through breakthrough infection (BI) and updated vaccination in overcoming antigenic imprinting needs to be determined. Participants in a long‐term follow‐up cohort of healthcare worker (HCW) vaccinee were categorized according to their infection/vaccination status. Anti‐SARS‐CoV‐2 spike/nucleocapsid protein antibodies were measured, and plaque reduction neutralization tests (PRNTs) against wild‐type (WT), BA.5, BN.1, and XBB.1.5 were conducted. The neutralization activity of intravenous immunoglobulin (IVIG) products was evaluated to assess the immune status of the general population. Ninety‐five HCWs were evaluated and categorized into seven groups. The WT PRNT ND50 value was highest regardless of infection/vaccination status, and groups with recent antigenic stimulation showed high PRNT titers overall. Groups with double Omicron stimulation, either by BI plus BA.4/5 bivalent vaccination or repeated BI, exhibited significantly higher BA.5 and BN.1 PRNT to WT PRNT ratios than those with single Omicron stimulation. Overall group immunity was estimated to be boosted in January 2023, reflecting the effect of the BA.4/5 bivalent booster and additional BIs, but slightly declined in June 2023. A substantial increase in the antibody concentrations of IVIG products was noticed in 2022, and recently produced IVIG products exhibited a substantial level of cross‐reactive neutralizing activity against emerging variants. Neutralizing activity against emerging variants could be enhanced by repeated antigenic stimulation via BI and/or updated vaccination. Overall group immunity was elevated accordingly, and IVIG products showed substantial activity against circulating strains. [ABSTRACT FROM AUTHOR]

Introduction: There is an evidence–practice gap in the optimal timing and volume of intravenous fluid as well as vasopressor administration in managing patients with sepsis. This study aimed to explore current hemodynamic resuscitation practice in emergency department (ED) for patients with sepsis and hypotension. Methods: This is a sub-analysis of the prospective multicentre ARISE FLUIDS observational study, which was conducted in 70 EDs across Australia and New Zealand. Baseline characteristics, as well as ED management and outcome of sepsis patients were compared between patients who were and were not admitted to intensive care unit (ICU) or high dependency unit (HDU). Results: A total of 587 patients with a median age of 65 years and even sex distribution (49% female) were available for analysis. Almost two-thirds of patients with sepsis (63.2%, n=371) were not admitted to ICU/HDU and were given lower intravenous (IV) fluid volumes over 24-hours, compared to those receiving critical care (4077ml vs. 5421ml, p

BackgroundNursing care residents have high hospitalization rates. To address this, we established a unique virtual geriatric unit that has developed a program aimed at providing support to nursing homes.AimsWe aimed to evaluate effectiveness of in-house intravenous antibiotic treatment in nursing hospitals after the implementation of the specially designed training program.MethodsA cohort study of nursing home residents to evaluate a training program for providers, designed to increase awareness and give practical tools for in-house treatment of acute infections. Data obtained included types of infections, antibiotics used, hospital transfer, and length of treatment. Primary outcomes were in-house recovery, hospitalization and mortality. Univariate analysis and multivariable logistic regression analysis to assess association between different factors and recovery.ResultsA total of 890 cases of acute infections were treated with intravenous antibiotics across 10 nursing homes over a total of 4,436 days. Of these cases, 34.8% were aged 90 years or older. Acute pneumonia was the most prevalent infection accounted for 354 cases (40.6%), followed by urinary tract infections (35.7%), and fever of presumed bacterial infection (17.1%). The mean duration of intravenous antibiotic treatment was 5.09 ± 3.86 days. Of the total cases, 800 (91.8%) recovered, 62 (7.1%) required hospitalization and nine (1.0%) resulted in mortality. There was no significant difference observed in recovery rates across different types of infections.DiscussionAppling a simple yet unique intervention program has led to more “in-house” residents receiving treatment, with positive clinical results.ConclusionTreating in-house nursing home residents with acute infections resulted in high recovery rates. Special education programs and collaboration between healthcare organizations can improve treatment outcomes and decrease the burden on the healthcare system.

Background Bisphosphonates are a class of medication commonly used to treat osteoporosis. Alendronate is recommended as the first-line treatment; however, long-term adherence (both treatment compliance and persistence) is poor. Alternative bisphosphonates are available, which can be given intravenously and have been shown to improve long-term adherence. However, the most clinically effective and cost-effective alternative bisphosphonate regimen remains unclear. What is the most cost-effective bisphosphonate in clinical trials may not be the most cost-effective or acceptable to patients in everyday clinical practice. Objectives Explore patient, clinician and stakeholder views, experiences and preferences of alendronate compared to alternative bisphosphonates. Update and refine the 2016 systematic review and cost-effectiveness analysis of bisphosphonates, and estimate the value of further research into their benefits. Undertake stakeholder/consensus engagement to identify important research questions and further rank research priorities. Methods The study was conducted in two stages, stages 1A and 1B in parallel, followed by stage 2: Stage 1A – we elicited patient and healthcare experiences to understand their preferences of bisphosphonates for the treatment of osteoporosis. This was undertaken by performing a systematic review and framework synthesis of qualitative studies, followed by semistructured qualitative interviews with participants. Stage 1B – we updated and expanded the existing Health Technology Assessment systematic review and clinical and cost-effectiveness model, incorporating a more comprehensive review of treatment efficacy, safety, side effects, compliance and long-term persistence. Stage 2 – we identified and ranked further research questions that need to be answered about the effectiveness and acceptability of bisphosphonates. Results Patients and healthcare professionals identified a number of challenges in adhering to bisphosphonate medication, balancing the potential for long-term risk reduction against the work involved in adhering to oral alendronate. Intravenous zoledronate treatment was generally more acceptable, with such regimens perceived to be more straightforward to engage in, although a portion of patients taking alendronate were satisfied with their current treatment. Intravenous zoledronate was found to be the most effective, with higher adherence rates compared to the other bisphosphonates, for reducing the risk of fragility fracture. However, oral bisphosphonates are more cost-effective than intravenous zoledronate due to the high cost of zoledronate administration in hospital. The importance of including patients and healthcare professionals when setting research priorities is recognised. Important areas for research were related to patient factors influencing treatment selection and effectiveness, how to optimise long-term care and the cost-effectiveness of delivering zoledronate in an alternative, non-hospital setting. Conclusions Intravenous zoledronate treatment was generally more acceptable to patients and found to be the most effective bisphosphonate and with greater adherence; however, the cost-effectiveness relative to oral alendronate is limited by its higher zoledronate hospital administration costs. Future work Further research is needed to support people to make decisions influencing treatment selection, effectiveness and optimal long-term care, together with the clinical and cost-effectiveness of intravenous zoledronate administered in a non-hospital (community) setting. Limitations Lack of clarity and limitations in the many studies included in the systematic review may have under-interpreted some of the findings relating to effects of bisphosphonates. Trial registration This trial is registered as ISRCTN10491361. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR127550) and is published in full in Health Technology Assessment; Vol. 28, No. 21. See the NIHR Funding and Awards website for further award information. Plain language summary Background Bisphosphonates are drug treatments commonly used to treat osteoporosis. Alendronate is the most used and is taken by mouth, weekly at a specific time of the week, which can be challenging. Less than one in four people continue this treatment beyond 2 years. Alternative bisphosphonates are available, which vary in frequency and how they are administered. The most acceptable and best value-for-money regimen is unclear. Aim Our aim was to determine how effective alternative bisphosphonates are compared to alendronate at preventing fractures and whether reduction in fracture risk was achieved at a reasonable financial cost, but acceptable to patients. Design and methods The study was conducted in two stages, stages 1A and 1B in parallel, followed by stage 2: Stage 1A: a review of the published evidence on patients’ and doctors’ views, experiences and preferences regarding different bisphosphonate treatment regimens, followed by interviews with patients and healthcare professionals. Stage 1B: an update of an existing study on how effective bisphosphonates are in preventing fragility fractures caused by osteoporosis and whether they are good value for money. Stage 2: identification of questions that need to be answered about the effectiveness and acceptability of bisphosphonate treatments. Results Taking bisphosphonate medication often involves quite a lot of effort by patients, particularly when taking alendronate tablets. A yearly infusion of zoledronate treatment was more acceptable, easier to engage with and the most effective treatment compared to alendronate. However, the cost of administering zoledronate in hospital made alendronate better value for money. Conclusions Bisphosphonates are effective in reducing the risk of fracture, but ‘continuing with treatment’, particularly alendronate tablets, remains a challenge. A yearly infusion of zoledronate offers an acceptable and effective treatment, but further research is needed to support patients and healthcare professionals in making decisions about the various treatments, benefits and cost savings of administering zoledronate outside of hospital and in the community. Scientific summary Background Alendronate (ALN) is recommended as the first-line osteoporosis treatment to prevent osteoporotic fractures; however, long-term adherence (both treatment compliance and persistence) is poor. Alternative bisphosphonates (BP) are available, which vary in frequency of use and/or route of administration and have been shown to improve long-term adherence compared to ALN. However, the most clinically effective and cost-effective alternative regimen remains unclear. Furthermore, clinicians should optimise dosing regimens on the basis of the patient’s understanding, preference and characteristics. What is the most cost-effective BP in clinical trials may not be the most cost-effective or acceptable to patients in everyday clinical practice. Objectives Explore patient, clinician and stakeholder views, experiences and preferences of ALN compared to alternative BP. Update and refine the 2016 systematic review and cost-effectiveness analysis of BP and estimate the value of further research into the relative benefits. Undertake stakeholder/consensus engagement to identify important research questions and further rank research priorities. Methods The study was conducted in two stages, stages 1A and 1B in parallel, followed by stage 2: Stage 1A: we elicited patient and clinician experiences of different BP regimens to understand their preferences and those of other stakeholders compared to ALN. This was undertaken by performing a systematic review and framework synthesis of qualitative studies around clinician and patient views, followed by semistructured qualitative interviews with multidisciplinary stakeholders. Stage 1B: we updated and expanded the existing Health Technology Assessment systematic review and clinical and cost-effective health economic model (2016), incorporating a more comprehensive review of treatment efficacy, safety, side effects, compliance and long-term persistence. The model takes a NHS and Personal Social Services perspective, with future costs and quality-adjusted life-years (QALYs) discounted at 3.5% per annum. Costs are reported in pound sterling based on 2021 prices. Stage 2: using an approach based on the James Lind methodology for identification and prioritisation of research questions, we identified questions that needed to be answered about the effectiveness and acceptability of BP. Findings from stages 1A and 1B, together with multidisciplinary meetings, identified areas of uncertainty. These questions were then ranked in a multidisciplinary, nationally representative stakeholder event, conducted online over MS Teams. Results We identified, through a systematic review of previous studies on patient and clinician experiences of BP treatment, how patients and healthcare professionals make sense (coherence) of BP by balancing perceptions of need against concerns, how uncertainty prevails about BP-perceived effectiveness and a number of individual and service factors that have potential to increase self-efficacy in recommending and adhering to BP. The qualitative interview study examining experiences of alternate BP regimens found that intravenous (IV) BP zoledronate (ZOL) treatment was generally more acceptable to patients. Such IV regimens were perceived to be more straightforward to engage in, although a portion of patients taking ALN were satisfied with their current treatment. The systematic review and network meta-analysis of previous studies of effectiveness found that IV ZOL was the most effective BP compared to ALN, risedronate and oral ibandronate for reducing the risk of fragility fractures. Adherence was higher in IV ZOL users. It was found that clinical decision-making could be facilitated by considering adherence patterns in BP users who were at increased risk of fracture. However, the higher hospital administration costs for IV ZOL meant that the incremental cost-effectiveness ratios for IV ZOL compared to ALN were greater than £30,000 per QALY across all risk categories. This was despite the fact that IV ZOL was predicted to result in fewer fractures than ALN, due to its higher treatment persistence and a longer offset period. The prioritisation exercise highlighted a need for further research to tackle the issues relating to patient factors influencing treatment selection and effectiveness, including in younger adults, how to optimise long-term care and support patient and clinician decision-making and the clinical and cost-effectiveness of giving IV ZOL in alternate settings to hospital care. Conclusions We have identified the factors that influence how patients and clinicians make sense of BP, described the experience of BP taking in terms of burden and identified factors that both facilitate and hinder confidence in taking and prescribing and monitoring BP. IV ZOL treatment was generally more acceptable to patients. IV ZOL was found to be the most effective BP and with greater adherence; however, the cost-effectiveness of IV ZOL relative to ALN was limited by the high hospital administration costs. Further research is needed to support people to make decisions influencing treatment selection and effectiveness and establish how to optimise long-term care. In addition, research is needed to explore the clinical and cost-effectiveness of IV ZOL delivered in alternate settings, such as in the community, compared to ALN treatment. Patient and public involvement We have worked closely with the Royal Osteoporosis Society (ROS) and the Nottingham ROS (NotROS) Support Group, who together have influenced the design of this application, choice of study outcomes and were involved throughout the study. Trial registration This trial is registered as ISRCTN10491361. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR127550) and is published in full in Health and Social Care Delivery Research; Vol. 28, No. 21. See the NIHR Funding and Awards website for further award information.

Background: The aim of this study was to assess whether intravenous dexamethasone was noninferior to perineural dexamethasone as an adjuvant to ropivacaine for a combination of saphenous and sciatic nerve blocks in patients undergoing foot and ankle surgery. Methods: This was a prospective, blinded, randomized noninferiority study. Seventy-five patients, aged 18–75 years, with an American Society of Anesthesiologists (ASA) physical status I-III who underwent foot and ankle surgery were involved. Patients scheduled for ultrasound-guided popliteal sciatic nerve block and saphenous nerve block were randomized to receive 0.375% ropivacaine with 7.5 mg of dexamethasone perineurally (Dex-PN), 10 mg of dexamethasone intravenously (Dex-IV) or neither (Placebo). The primary outcome was the duration of analgesia. The major secondary outcomes were the composite pain intensity and opioid consumption score at 0–48 h intervals after anesthesia. Results: The mean analgesic duration was 26.2 h in the Dex-IV group and 27.9 h in the Dex-PN group (duration difference, −1.7; 95% CI, −3.8 to 0.43; P = 0.117), and both durations were significantly longer than that in the placebo group (17.6 h, P

Background: This randomized and controlled prospective study tested the hypothesis that closed-loop Target-Controlled Infusion (TCI) of propofol would be associated with better system performance when compared with open-loop controlled delivery of propofol. Methods: Patients scheduled for elective breast surgery were randomly assigned to two groups: a closed-loop group, in which propofol infusion was performed by a closed-loop TCI system that used the Bispectral Index (BIS) as a feedback parameter to titrate the rate of propofol infusion, and an open-loop group, in which propofol infusion was performed manually and guided by the bispectral index. Results: A total of 156 patients were recruited for this study (closed-loop group n = 79; open-loop group n = 77). The Global Score (GS) of the closed-loop group was lower than that of the open-loop group (34.3 and 42.2) (p = 0.044). The proportions of time with a BIS value between 40 and 60 were almost identical in the closed-loop group and the open-loop group (68.7 ± 10.6% and 66.7 ± 13.3%) (p = 0.318). The individuals in the closed-loop group consumed more propofol compared with those in the open-loop group (7.20 ± 1.65 mg.kg−1.h−1 vs. 6.03 ± 1.31 mg.kg−1.h−1, p < 0.001). No intraoperative recall, somatic events or adverse events occurred. No significant difference in heart rate was observed between the two groups (p = 0.169). Conclusion: The closed-loop protocol was associated with lower BIS variability and lower out-of-range BIS values, at the cost of a greater consumption of propofol when compared to the open loop group. Register number: ChiCTR-INR-17010399.

Aims: The PARAMEDIC-3 trial evaluates the clinical and cost-effectiveness of an intraosseous first strategy, compared with an intravenous first strategy, for drug administration in adults who have sustained an out-of-hospital cardiac arrest. Methods: PARAMEDIC-3 is a pragmatic, allocation concealed, open-label, multi-centre, superiority randomised controlled trial. It will recruit 15,000 patients across English and Welsh ambulance services. Adults who have sustained an out-of-hospital cardiac arrest are individually randomised to an intraosseous access first strategy or intravenous access first strategy in a 1:1 ratio through an opaque, sealed envelope system. The randomised allocation determines the route used for the first two attempts at vascular access. Participants are initially enrolled under a deferred consent model.The primary clinical-effectiveness outcome is survival at 30-days. Secondary outcomes include return of spontaneous circulation, neurological functional outcome, and health-related quality of life. Participants are followed-up to six-months following cardiac arrest. The primary health economic outcome is incremental cost per quality-adjusted life year gained. Conclusion: The PARAMEDIC-3 trial will provide key information on the clinical and cost-effectiveness of drug route in out-of-hospital cardiac arrest.Trial registration: ISRCTN14223494, registered 16/08/2021, prospectively registered.

AbstractThe impact of preexposure prophylaxis uptake on sexual and injection-related behaviors among women who inject drugs is poorly understood. Over 24 weeks, preexposure prophylaxis uptake among women who inject drugs was associated with increased sharing of injection equipment but not syringes and no changes in condomless sex, providing limited evidence of risk compensation in this vulnerable population.

ObjectiveUnintentional drug poisoning and overdose deaths in New York City (NYC) increased 175% between 2010 and 2017, partly due to the transition from noninjectable opioids to heroin injection. This transition has led to concern of a resurgent HIV epidemic among persons who inject drugs (PWID) in NYC. Thus, we sought to characterize HIV transmission dynamics in PWID.DesignGenetic network analysis of HIV-1 public health surveillance data.MethodsWe analyzed HIV diagnoses reported to public health surveillance to determine the trajectory of the HIV epidemic among PWID in NYC, from 1985 through 2019. Genetic distance-based clustering was performed using HIV-TRACE to reconstruct transmission patterns among PWID.ResultsThe majority of the genetic links to PWID diagnosed in the 1980s and 1990s are to other PWID. However, since 2011, there has been a continued decline in new diagnoses among PWID, and genetic links between PWID have become increasingly rare, although links to noninjecting MSM and other people reporting sexual transmission risk have become increasingly common. However, we also find evidence suggestive of a resurgence of genetic links among PWID in 2018-2019. PWID who reported male-male sexual contact were not preferentially genetically linked to PWID over the surveillance period, emphasizing their distinct risk profile from other PWID.ConclusionThese trends suggest a transition from parenteral to sexual transmission among PWID in NYC, suggesting that harm reduction, syringe exchange programs, and legalization of over-the-counter syringe sales in pharmacies have mitigated HIV risk by facilitating well tolerated injection among new PWID.

BackgroundPeople who inject drugs (PWID) are at high risk for hepatitis C virus (HCV) infection and its complications in many countries, including Iran. This pilot study aimed to evaluate the effect of a community-based HCV model of care on HCV testing and treatment initiation among PWID in Kerman, Iran.MethodsThis study is part of the Rostam study and is a non-randomized trial evaluating the effect of on-site HCV- antibody rapid testing, venipuncture for HCV RNA testing, and treatment eligibility assessment on HCV testing and treatment initiation among PWID. Recruitment, interviews, and HCV screening, diagnosis, and treatment were all conducted at a community-based drop-in center (DIC) serving PWID clients.ResultsA total of 171 PWID (median age of 39 years and 89.5% male) were recruited between July 2018 and May 2019. Of 62 individuals who were HCV antibody positive, 47 (75.8%) were HCV RNA positive. Of RNA-positive individuals, 36 (76.6%) returned for treatment eligibility assessment. Of all the 36 participants eligible for treatment, 34 (94.4%) initiated HCV antiviral therapy. A sustained virologic response at 12 weeks post-treatment was 76.5% (26/34) in the intention-to-treat (ITT group) analysis and 100% (23/23) in the per-protocol (PP group) analysis.ConclusionOur integrated on-site community-based HCV care model within a DIC setting suggested that HCV care including HCV testing and treatment uptake can be successfully delivered outside of hospitals or specialized clinics; a model which is more likely to reach PWID and can provide significant progress towards HCV elimination among this population.

BackgroundSharp exacerbations of the US overdose crisis are linked to polysubstance use of synthetic compounds. Xylazine is a veterinary tranquilizer, long noted in the street opioid supply of Puerto Rico, and more recently Philadelphia. Yet its national trends, geographic distribution, and health risks are poorly characterized.MethodsIn this sequential mixed-methods study, xylazine was increasingly observed by ethnographers in Philadelphia among drug-sellers and people who inject drugs (PWID). Subsequently, we systematically searched for records describing xylazine-present overdose mortality across the US and assessed time trends and overlap with other drugs.ResultsIn 10 jurisdictions - representing all four US Census Regions - xylazine was increasingly present in overdose deaths, rising from 0.36% of deaths in 015m 6.7% in 2020. The highest xylazine prevalence data was observed in Philadelphia, (25.8% of deaths), followed by Maryland (19.3%) and Connecticut (10.2%). Illicitly-manufactured-fentanyls were present in 98.4% of xylazine-present-overdose-deaths - suggesting a strong ecological link - as well as cocaine (45.4%), benzodiazepines (28.4%), heroin (23.3%), and alcohol (19.7%). PWID in Philadelphia described xylazine as a sought-after adulterant that lengthens the short duration of fentanyl injections. They also linked it to increased risk of soft tissue infection and naloxone-resistant overdose.ConclusionsXylazine is increasingly present in overdose deaths, linked to the proliferation of illicitly-manufactured-fentanyls. Ethnographic accounts associate it with profound risks for PWID. Nevertheless, many jurisdictions do not routinely test for xylazine, and it is not comprehensively tracked nationally. Further efforts are needed to provide PWID with services that can help minimize additional risks associated with a shifting drug supply.

BackgroundThe current opioid epidemic across the United States has fueled a surge in the rate of new hepatitis C virus (HCV) infections among young persons who inject drugs (PWIDs). Paramount to interrupting transmission is targeting these high-risk populations and understanding the underlying network structures facilitating transmission within these communities.MethodsDeep sequencing data were obtained for 52 participants from 32 injecting partnerships enrolled in the U-Find-Out (UFO) Partner Study, which is a prospective study of self-described injecting dyad partnerships from a large community-based study of HCV infection in young adult PWIDs from San Francisco. Phylogenetically linked transmission events were identified using traditional genetic-distance measures and viral deep sequence phylogenies reconstructed to determine the statistical support of inferences and the direction of transmission within partnerships.ResultsUsing deep sequencing data, we found that 12 of 32 partnerships were genetically similar and clustered. Three additional phylogenetic clusters were found describing novel putative transmission links outside of the injecting relationship. Transmission direction was inferred correctly for 5 partnerships with the incorrect transmission direction inferred in more than 50% of cases. Notably, we observed that phylogenetic linkage was most often associated with a lower number of network partners and involvement in a sexual relationship.ConclusionsDeep sequencing of HCV among self-described injecting partnerships demonstrates that the majority of transmission events originate from outside of the injecting partnership. Furthermore, these findings caution that phylogenetic methods may be unable to routinely infer the direction of transmission among PWIDs especially when transmission events occur in rapid succession within high-risk networks.

IntroductionInjection drug use initiation is commonly facilitated by other people who inject drugs (PWID). We investigated how the gender of PWID influences their risk of providing initiation assistance to others across two distinct geo-cultural settings.MethodsData were drawn from two prospective cohorts in Tijuana, Mexico and Vancouver, Canada which conducted semi-annual interviews within the PReventing Injecting by Modifying Existing Responses (PRIMER) study. Participants consisted of PWID who had reported never providing injection initiation assistance at baseline. We then conducted site-specific discrete-time survival analyses assessing the relationship between gender and other relevant covariates (e.g. age and past 6-month sex work) on the risk of the first reported instance of providing initiation assistance.ResultsOf 1988 PWID (Tijuana: n = 596; Vancouver: n = 1392), 256 (43%) and 511 (36.7%) participants were women, and 42 (1.7%) and 78 (1.6%) reported recent injection initiation assistance across a median of three and two follow-up visits, respectively. Women had a lower risk of providing injection initiation assistance for the first time in Tijuana (adjusted hazard ratio = 0.52, 95% confidence interval 0.27-0.99), but not in Vancouver. Gendered pathways, like sex work, were associated with providing initiation assistance for the first time in Vancouver (adjusted hazard ratio = 1.97, 95% confidence interval 1.08-3.61).Discussion and conclusionsWomen in Tijuana, but not Vancouver, were less likely to provide first-time initiation assistance among PWID. These results can inform gender- and site-specific prevention efforts aimed at reducing transitions into drug injecting across geographic contexts.

Jeongwon Han,1 Hanna Lee2 1College of Nursing Science, Kyung Hee University, Seoul, Republic of Korea; 2Department of Nursing, Gangneung-Wonju National University, Gangwon‑do, Republic of KoreaCorrespondence: Hanna Lee, Department of Nursing, Gangneung-Wonju National University, 150, Namwon-ro, Heungeop-myeon, Wonju-si, Gangwon-do, 2640, Republic of Korea, Tel +82 33 760 8655, Fax +82 33 760 8641, Email hannalee@gwnu.ac.krPurpose: This pilot study aimed to provide basic data on intravenous infusion nursing by analyzing the infusion rate in the cephalic and median cubital veins depending on the height of the infusion bag and inner diameter of the peripheral venous catheter (PVC).Methods: While infusing 0.9% normal saline at 22 °C (room temperature) into elbow cephalic and median cubital veins, the infusion rate may be controlled by adjusting the fluid height and PVC diameter. To assess the validity of the laminar flow assumption, the study estimated the Reynolds number (Re) using the velocity obtained by applying Bernoulli’s equation considering the friction coefficient.Results: At a constant fluid height, the infusion rate increased with increasing PVC diameter. At a constant PVC diameter, the infusion rate increased with increasing fluid height. In a comparison between the cephalic and median cubital veins at constant fluid height and PVC diameter, the solution was infused at a higher rate into the cephalic vein, which was under lower venous pressure.Conclusion: The analysis of the infusion rate according to fluid height and PVC diameter provided basic data on intravenous infusion nursing. The results are expected to provide evidence for the standardization of intravenous infusion nursing.Keywords: catheterization, infusions, intravenous, nursing, patients

Abstract Background A error in intravenous injection in pediatric wards can cause irreparable injuries. This study aimed to determine the level of knowledge and performance of nurses in terms of preparation and injection of intravenous drugs in pediatric wards of hospitals affiliated to Isfahan University of Medical Sciences. Methods This cross-sectional study was conducted in 2022 on 156 nurses working in pediatric wards. The data was collected with demographic information questionnaire and the knowledge and performance of the participants were determined using a researcher-made questionnaire, including the five rights of medication administration (preparation and injection, medication error, drug side effects, family empowerment, and documentation) using self-reporting and observation methods. Formal and content validity was calculated using the opinions of 10 experts and Cronbach's alpha with 40 samples. Results The mean and standard deviation of total nurses' knowledge and performance scores were 58.31 + 10.1 and 66.1 + 14.4, respectively. Moreover, the mean and standard deviation of nurses' knowledge scores were 63.55 + 14.3 for documentation, 46.1 + 7.9 for preparation and injection, 73.9 + 12.3 for drug side effects, 58.4 + 10.2 for medication error, and 69.4 + 9.4 for family empowerment. Besides, the mean performance was 69.1 + 17.6 for documentation, 61.3 ± 9.9 for preparation and injection, 78.21 + 12 for drug side effects, 58.6 + 15 for medication error, and 65.4 + 17.7 for family empowerment. Conclusion The results showed that the mean knowledge and pharmacological performance of nurses working in pediatric wards in different areas of the principles of medicine were not at the desired level, and this can affect children adversely.

Abstract Background Evolving mutations of the novel coronavirus continue to fuel up the pandemic. The virus affects the human respiratory system along with other body systems, causing several sequelae in the survivors of the disease, presented as post-COVID-19 syndrome or long-COVID-19. This protocol utilized Hope Biosciences’ autologous, adipose-derived mesenchymal stem cells (HB-adMSCs) to evaluate safety and efficacy of HB-adMSC therapy to improve signs and symptoms associated with post-COVID-19 syndrome. Methods Ten eligible subjects with post-COVID-19 syndrome were enrolled in the program for a duration of 40 weeks who received 5 intravenous infusions of 2 × 108 autologous HB-adMSCs each at week 0, 2, 6, 10 and 14 with a follow-up at week 18 and end of the study at week 40. Safety assessments included incidence of adverse and serious adverse events along with the laboratory measures of hematologic, hepatic, and renal function. Efficacy was examined by quality-of-life assessments, fatigue assessments, Visual analog scale (VAS) of symptoms and monitoring of respiration and oxygen saturation rates. Results VAS scores and Fatigue Assessment scores (FAS) showed significant improvements post-treatment (P = 0.0039, ES = 0.91) compared to baseline. Respiration rates and oxygen saturation levels that were within the normal range at the baseline remained unchanged at the end of the study (EOS). Paired comparison between baseline and EOS for short-form-36 health survey questionnaire (SF-36) scores also showed improved quality-of-life with significant improvements in individual SF-36 evaluations. Mostly mild AEs were reported during the study period with no incidence of serious AEs. Also, no detrimental effects in laboratory values were seen. Conclusions The results of the expanded access program indicated that treatment with autologous HB-adMSCs resulted in significant improvements in the signs and symptoms associated with post-COVID-19 syndrome as assessed by VAS and FAS scores. Additionally, improvements in the patients’ quality-of-life as demonstrated using SF-36 scores that also showed significant improvements in individual scaled scores. Overall, administration of multiple infusions of autologous HB-adMSCs is safe and efficacious for improvements in the quality-of life of patients with post-COVID-19 syndrome. Trial registration: Clinical trial registration number: NCT04798066. Registered on March 15, 2021. ( https://clinicaltrials.gov/ct2/show/NCT04798066?term=hope+biosciences&cond=Post-COVID-19+Syndrome&draw=2&rank=2 ).

Abstract Background Diligent fluid management is an instrumental part of Enhanced Recovery After Surgery. However, the effect of a ward regimen to limit intravenous fluid administration on outcome remains unclear. We performed a meta-analysis investigating the effect of a restrictive versus a conventional fluid regimen on complications in patients after non-cardiac surgery in the postoperative period on the clinical ward. Study design We performed a systematic search in MEDLINE, Embase, Cochrane Library, and CINAHL databases, from the start of indexing until June 2022, with constraints for English language and adult human study participants. Data were combined using classic methods of meta-analyses and were expressed as weighted pooled risk ratio (RR) or odds ratio (OR) with 95% confidence interval (CI). Quality assessment and risk of bias analyses was performed according to PRISMA guidelines. Results Seven records, three randomized controlled trials, and four non-randomized studies were included with a total of 883 patients. A restrictive fluid regimen was associated with a reduction in overall complication rate in the RCTs (RR 0.46, 95% CI 0.23 to 0.95; P

Abstract Background The purpose of this study was to investigate the effect of intravenous (IV) dexamethasone on the duration of hyperbaric bupivacaine spinal anesthesia. Methods Two hundred patients between the ages of 18 and 60, of both sexes with ASA I- II classification scheduled for lower abdominal surgery under spinal anesthesia using hyperbaric bupivacaine 0.5% were randomly divided into two groups: the dexamethasone group (Dexa group) and the control group, with 100 patients in each group. Before the administration of spinal anesthesia, the Dexa group received an intravenous infusion of 8 mg dexamethasone in 500 mL normal saline, while the control group received 500 mL normal saline only. The primary outcome of this study was to assess the effect of IV dexamethasone on the regression of hyperbaric bupivacaine spinal anesthesia. Secondary outcome measures included the total duration of sensory and motor blocks, VAS score, time of first analgesic request, total analgesic consumption within the first 24 h, and the occurrence of any side effects. Results The Dexa group had significantly delayed onset of 2 dermatomes regression (P

Abstract Background Biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) are highly effective in treating rheumatoid arthritis (RA), albeit high drug cost has restricted their use in many countries. As a countermeasure, Norway implemented pharmaceutical tendering as a cost-reducing strategy. The aim of this study was to assess the annual proportion of different b/tsDMARDs registered to treat RA patients under the influence of a Norwegian pharmaceutical tendering between 2010 and 2019. Method The data is collected from ten Norwegian outpatient centers. The included patients are categorized as naïve, non-naïve, and current b/tsDMARD users. 13 individual b/tsDMARDs are assessed and compared with the tender rankings from each year. Overview of subcutaneous (sc) with per oral vs. intravenous (iv) and biosimilars vs. non-biosimilar are also described. Result The tender-winning b/tsDMARD was the most or second most used drug in nine out of ten years for naïve users, seven for non-naïve users, and twice for current users. The average sum of the highest and second highest proportion among naïve, non-naïve, and current b/tsDMARD users were 75%, 53%, and 50% during the ten years, respectively. The tender-winning drug was iv in eight out of ten years. However, the average total proportion of sc and per oral b/tsDMARDs was about 70% for naïve b/tsDMARD users, 50% for non-naïve b/tsDMARD users, and 60% for current b/tsDMARD users. The main contributors to sc and per oral b/tsDMARD were etanercept (reference and biosimilar) and certolizumab pegol. The main contributors to iv b/tsDMARD were rituximab reference and infliximab biosimilar. Despite low-ranking offers, rituximab reference (offered as a second-line drug) often achieved a high proportion among non-naïve and current b/tsDMARD users. After the introduction of biosimilars, their average proportion was about 40%, 40%, and 20% for naïve, non-naïve, and current b/tsDMARD users, respectively. Conclusion Based on observed data, a higher tender rank was associated with a higher proportion among naïve and non-naïve b/tsDMARD users. However, in most cases, sc b/tsDMARDs achieved a higher proportion with lower tender ranks than iv b/tsDMARDs with higher tender ranks.

Abstract Background Postoperative cognitive dysfunction (POCD) has been reported as a significant complication in elderly patients. Various methods have been proposed for reducing the incidence and severity of POCD. Intravenous lidocaine administration has been reported in the literature to reduce POCD, but the effect of lidocaine remains controversial. Methods We screened Medline, Embase, Cochrane Library, and China National Knowledge Infrastructure (up to April 2022) databases following a search strategy for intravenous lidocaine on POCD. We also screened related bibliographies on lidocaine for POCD. Ten articles comprising 1517 patients were selected and analyzed. We divided the postoperative follow-up period as follows: short term (90 days). Outcomes We found that lidocaine could attenuate the overall incidence of POCD, especially in the short term. There were no differences between lidocaine and placebo on the overall severity of POCD. Conclusion Lidocaine administered intravenously could attenuate the overall incidence of POCD and its severity in the short term.

Allopregnanolone (ALLO) is a neurosteroid that modulates synaptic and extrasynaptic GABAA receptors. We hypothesize that ALLO may be useful as first-line treatment of status epilepticus (SE). Our objectives were to (1) characterize ALLO pharmacokinetics-pharmacodynamics PK-PD after intravenous (IV) and intramuscular (IM) administration and (2) compare IV and IM ALLO safety and tolerability. Three healthy dogs and two with a history of epilepsy were used. Single ALLO IV doses ranging from 1-6 mg/kg were infused over 5 minutes or injected IM. Blood samples, vital signs, and sedation assessment were collected up to 8 hours postdose. Intracranial EEG (iEEG) was continuously recorded in one dog. IV ALLO exhibited dose-proportional increases in exposure, which were associated with an increase in absolute power spectral density in all iEEG frequency bands. This relationship was best described by an indirect link PK-PD model where concentration-response was described by a sigmoidal maximum response (Emax) equation. Adverse events included site injection pain with higher IM volumes and ataxia and sedation associated with higher doses. IM administration exhibited incomplete absorption and volume-dependent bioavailability. Robust iEEG changes after IM administration were not observed. Based on PK-PD simulations, a 2 mg/kg dose infused over 5 minutes is predicted to achieve plasma concentrations above the EC50, but below those associated with heavy sedation. This study demonstrates that ALLO is safe and well tolerated when administered at 1-4 mg/kg IV and up to 2 mg/kg IM. The rapid onset of effect after IV infusion suggests that ALLO may be useful in the early treatment of SE. SIGNIFICANCE STATEMENT: The characterization of the pharmacokinetics and pharmacodynamics of allopregnanolone is essential in order to design clinical studies evaluating its effectiveness as an early treatment for status epilepticus in dogs and people. This study has proposed a target dose/therapeutic range for a clinical trial in canine status epilepticus.

Background Transplacental fetal treatment of immune-mediated fetal heart disease, including third-degree atrioventricular block (AVB III) and endocardial fibroelastosis, is controversial. Methods and Results To study the impact of routine transplacental fetal treatment, we reviewed 130 consecutive cases, including 108 with AVB III and 22 with other diagnoses (first-degree/second-degree atrioventricular block [n=10]; isolated endocardial fibroelastosis [n=9]; atrial bradycardia [n=3]). Dexamethasone was started at a median of 22.4 gestational weeks. Additional treatment for AVB III included the use of a β-agonist (n=47) and intravenous immune globulin (n=34). Fetal, neonatal, and 1-year survival rates with AVB III were 95%, 93%, and 89%, respectively. Variables present at diagnosis that were associated with perinatal death included an atrial rate

BackgroundParaneoplastic limbic encephalitis is a rare neurologic syndrome that affects patients with cancer and commonly presents with symptoms of personality changes, visual disturbances, seizures, vertigo, and memory loss. It has an immune-mediated pathophysiology and is associated with antibodies directed against both the tumor and limbic structures in the nervous system. Here, we report a case of paraneoplastic limbic encephalitis with an unusual presentation with initial symptoms of panhypopituitarism.Case presentationA 28-year-old Caucasian man with history of testicular cancer in remission for almost 2 years was admitted to our hospital for altered mental status, syncope, vertical gaze palsy, ataxia, and tremor. Three months prior to admission, he began to have initial symptoms of fatigue, weight gain, and hypogonadism. A few weeks before admission, he also developed worsening neurological symptoms that led him to present to the hospital. While hospitalized, he had an episode of syncope. Evaluation of his syncope revealed that he was hypovolemic due to polyuria, concerning for diabetes insipidus. While the patient did not meet criteria for diabetes insipidus, further endocrine laboratory testing to evaluate his central hormonal axes revealed panhypopituitarism. He also underwent a neurologic work-up with brain magnetic resonance imaging and lumbar puncture, with results consistent with encephalitis. He received high-dose steroids, plasmapheresis, and intravenous immunoglobulin, which did not significantly improve his physical examination or mental status. Extensive testing did not show any recurrence of his testicular cancer. Paraneoplastic antibodies were also ordered, with anti-Ma2 antibodies eventually returning positive, consistent with anti-Ma2 paraneoplastic limbic encephalitis.ConclusionParaneoplastic limbic encephalitis is often a difficult diagnosis due to its variable presentation and timeline of presentation, leading to delays in both diagnosis and treatment. While paraneoplastic limbic encephalitis usually presents with neurological symptoms, it may also present with panhypopituitarism. A high index of suspicion is warranted for paraneoplastic syndromes in patients with history of malignancy, even if the malignancy is in remission.

Pathogenesis of lung injury in COVID-19 is not completely understood, leaving gaps in understanding how current treatments modulate the course of COVID-19. Neutrophil numbers and activation state in circulation have been found to correlate with COVID-19 severity, and neutrophil extracellular traps (NETs) have been found in the lung parenchyma of patients with acute respiratory distress syndrome (ARDS) in COVID-19. Targeting the pro-inflammatory functions of neutrophils may diminish lung injury in COVID-19 and ARDS. Neutrophils were isolated from peripheral blood of healthy donors, treated ex vivo with dexamethasone, tocilizumab and intravenous immunoglobulin (IVIG) and NET formation, oxidative burst, and phagocytosis were assessed. Plasma from critically ill COVID-19 patients before and after clinical treatment with IVIG and from healthy donors was assessed for neutrophil activation-related proteins. While dexamethasone and tocilizumab did not affect PMA- and nigericin-induced NET production ex vivo, IVIG induced a dose-dependent abrogation of NET production in both activation models. IVIG also reduced PMA-elicited reactive oxygen species production, but did not alter phagocytosis. COVID-19 patients were found to have elevated levels of cell-free DNA, neutrophil elastase and IL-8 as compared to healthy controls. Levels of both cell-free DNA and neutrophil elastase were lower 5 days after 4 days of daily treatment with IVIG. The lack of impact of dexamethasone or tocilizumab on these neutrophil functions suggests that these therapeutic agents may not act through suppression of neutrophil functions, indicating that the door might still be open for the addition of a neutrophil modulator to the COVID-19 therapeutic repertoire.

Receptor tyrosine-protein kinase ERBB3 (HER3) is expressed in most EGFR-mutated lung cancers but is not a known mechanism of resistance to EGFR inhibitors. HER3-DXd is an antibody-drug conjugate consisting of a HER3 antibody attached to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker. This phase I, dose escalation/expansion study included patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) with prior EGFR tyrosine kinase inhibitor (TKI) therapy. Among 57 patients receiving HER3-DXd 5.6 mg/kg intravenously once every 3 weeks, the confirmed objective response rate by blinded independent central review (Response Evaluation Criteria in Solid Tumors v1.1) was 39% [95% confidence interval (CI), 26.0-52.4], and median progression-free survival was 8.2 (95% CI, 4.4-8.3) months. Responses were observed in patients with known and unknown EGFR TKI resistance mechanisms. Clinical activity was observed across a broad range of HER3 membrane expression. The most common grade ≥3 treatment-emergent adverse events were hematologic toxicities. HER3-DXd has clinical activity in EGFR TKI-resistant cancers independent of resistance mechanisms, providing an approach to treat a broad range of drug-resistant cancers. SIGNIFICANCE: In metastatic EGFR-mutated NSCLC, after disease progression on EGFR TKI therapy, treatment approaches include genotype-directed therapy targeting a known resistance mechanism or chemotherapy. HER3-DXd demonstrated clinical activity spanning known and unknown EGFR TKI resistance mechanisms. HER3-DXd could present a future treatment option agnostic to the EGFR TKI resistance mechanism.See related commentary by Lim et al., p. 16.This article is highlighted in the In This Issue feature, p. 1.

IntroductionMapping and population size estimates of people who inject drugs (PWID) provide information needed for monitoring coverage of programs and planning interventions. The objectives of this study were to provide the locations and numbers of PWID in eight cities in Afghanistan and extrapolate estimates for the country as a whole.MethodsMultiple population size estimation methods were used, including key informant interviews for mapping and enumeration with reverse tracking, unique object and service multipliers, capture-recapture, and wisdom of the crowds. The results of the several methods were synthesized using the Anchored Multiplier-a Bayesian approach to produce point estimates and 95% credible intervals (CI). Using the prevalence of PWID in the eight cities and their correlation with proxy indicators, we extrapolated the PWID population size for all of Afghanistan.ResultsKey informants and field mapping identified 374 hotspots across the eight cities from December 29, 2018 to March 20, 2019. Synthesizing results of the multiple methods, the number of male PWID in the eight study cities was estimated to be 11,506 (95% CI 8,449-15,093), corresponding to 0.69% (95% CI 0.50-0.90) of the adult male population age 15-64 years. The total number of women who injected drugs was estimated at 484 (95% CI 356-633), corresponding to 0.03% (95% CI 0.02-0.04) of the adult female population. Extrapolating by proxy indicators, the total number of PWID in Afghanistan was estimated to be 54,782 (95% CI 40,250-71,837), men and 2,457 (95% CI 1,823-3,210) women. The total number of PWID in Afghanistan was estimated to be 57,207 (95% CI 42,049-75,005), which corresponds to 0.37% (95% CI 0.27-0.48) of the adult population age 15 to 64 years.DiscussionThis study provided estimates for the number of PWID in Afghanistan. These estimates can be used for advocating and planning services for this vulnerable at-risk population.

BackgroundPeople who inject drugs (PWID) have low rates of COVID-19 testing and vaccination and are vulnerable to severe disease. We partnered with a local, community-based syringe service program (SSP) in San Diego County, CA, to develop the single-session theory- and evidence-informed "LinkUP" intervention to increase COVID-19 testing and vaccination. This paper details the protocol for a pilot randomized controlled trial (RCT) of the LinkUP intervention.MethodsWith significant community input into study design considerations, including through our Community and Scientific Advisory Board, the LinkUP pilot RCT leverages an ongoing cohort study with adult (≥ 18 years) PWID in San Diego County to recruit participants who have not recently undergone voluntary COVID-19 testing and are unvaccinated. Eligible participants are referred to SSP locations randomized to offer the active intervention (involving tailored education, motivational interviewing, and problem-solving strategies) or a didactic attention-control condition (information sharing only). Both conditions are delivered by trained peer counselors hired by the SSP and were designed to be delivered at mobile (outdoor) SSP sites in ~ 30 min. Intake data assesses COVID-19 testing and vaccination history, health status, and harm reduction needs (to facilitate SSP referrals). At the end of either intervention condition, peer counselors offer onsite rapid COVID-19 antigen testing and COVID-19 vaccination referrals. Out-take and follow-up data (via SSP and state health department record linkages) confirms whether participants received the intervention, COVID-19 testing (and results) onsite or within six months, and vaccination referrals (and uptake) within six months. Planned analyses, which are not powered to assess efficacy, will provide adequate precision for effect size estimates for primary (COVID-19 testing) and secondary (vaccination) intervention outcomes. Findings will be disseminated widely including to local health authorities, collaborating agencies, and community members.DiscussionLessons from this community-based pilot study include the importance of gathering community input into study design, cultivating research-community partnerships based on mutual respect and trust, and maintaining frequent communication regarding unexpected events (e.g., police sweeps, neighborhood opposition). Findings may support the adoption of COVID-19 testing and vaccination initiatives implemented through SSPs and other community-based organizations serving vulnerable populations of people impacted by substance use and addiction. Trial registration This trial was registered prospectively at ClinicalTrials.gov (identifier NCT05181657).

BackgroundSARS-CoV-2 prevalence is elevated among people who inject drugs (PWID). In Tijuana, Mexico, COVID-19 vaccines became available to the general population in June 2021, but uptake among PWID was

BackgroundIn 2017, San Francisco's initiative to locally eliminate hepatitis C virus (HCV) as a public health threat, End Hep C SF, generated an estimate of city-wide HCV prevalence in 2015, but only incorporated limited information about population HCV treatment. Using additional data and updated methods, we aimed to update the 2015 estimate to 2019 and provide a more accurate estimate of the number of people with untreated, active HCV infection overall and in key subgroups-people who inject drugs (PWID), men who have sex with men (MSM), and low socioeconomic status transgender women (low SES TW).MethodsOur estimates are based on triangulation of data from blood bank testing records, cross-sectional and longitudinal observational studies, and published literature. We calculated subpopulation estimates based on biological sex, age and/or HCV risk group. When multiple sources of data were available for subpopulation estimates, we calculated an average using inverse variance weighting. Plausible ranges (PRs) were conservatively estimated to convey uncertainty.ResultsThe total number of people estimated to have anti-HCV antibodies in San Francisco in 2019 was 22,585 (PR:12,014-44,152), with a citywide seroprevalence of 2.6% (PR:1.4%-5.0%)-similar to the 2015 estimate of 21,758 (PR:10,274-42,067). Of all people with evidence of past or present infection, an estimated 11,582 (PR:4,864-35,094) still had untreated, active HCV infection, representing 51.3% (PR:40.5%-79.5%) of all people with anti-HCV antibodies, and 1.3% (PR:0.6%-4.0%) of all San Franciscans. PWID comprised an estimated 2.8% of the total population of San Francisco, yet 73.1% of people with anti-HCV antibodies and 90.4% (n = 10,468, PR:4,690-17,628) of untreated, active HCV infections were among PWID. MSM comprised 7.8% of the total population, yet 11.7% of people with anti-HCV antibodies and 1.0% (n = 119, PR:0-423) of those with untreated active infections. Low SES TW comprised an estimated 0.1% of the total population, yet 1.4% of people with HCV antibodies and 1.6% (n = 183, PR:130-252) of people with untreated active infections.ConclusionsDespite the above-average number (2.6%) of people with anti-HCV antibodies, we estimate that only 1.3% (PR:0.6%-4.0%) of all San Francisco residents have untreated, active HCV infection-likely a reflection of San Francisco's robust efforts to diagnose infection among high-risk groups and initiate curative treatment with as many people as possible. While plausible ranges of infections are wide, these findings indicate that while the overall number of people with anti-HCV antibodies may have increased slightly, the number of people with active HCV infection may have decreased slightly since 2015. This estimate improves upon the 2015 calculations by directly estimating the impact of curative treatment citywide and in subgroups. However, more research is needed to better understand the burden of HCV disease among other subgroups at high risk, such as Blacks/African Americans, people with a history of injection drug use (but not injecting drugs in the last 12 months), people who are currently or formerly incarcerated, and people who are currently or formerly unhoused.

The antibody profile against autoantigens previously associated with autoimmune diseases and other human proteins in patients with COVID-19 or multisystem inflammatory syndrome in children (MIS-C) remains poorly defined. Here we show that 30% of adults with COVID-19 had autoantibodies against the lung antigen KCNRG, and 34% had antibodies to the SLE-associated Smith-D3 protein. Children with COVID-19 rarely had autoantibodies; one of 59 children had GAD65 autoantibodies associated with acute onset of insulin-dependent diabetes. While autoantibodies associated with SLE/Sjögren's syndrome (Ro52, Ro60, and La) and/or autoimmune gastritis (gastric ATPase) were detected in 74% (40/54) of MIS-C patients, further analysis of these patients and of children with Kawasaki disease (KD), showed that the administration of intravenous immunoglobulin (IVIG) was largely responsible for detection of these autoantibodies in both groups of patients. Monitoring in vivo decay of the autoantibodies in MIS-C children showed that the IVIG-derived Ro52, Ro60, and La autoantibodies declined to undetectable levels by 45-60 days, but gastric ATPase autoantibodies declined more slowly requiring >100 days until undetectable. Further testing of IgG and/or IgA antibodies against a subset of potential targets identified by published autoantigen array studies of MIS-C failed to detect autoantibodies against most (16/18) of these proteins in patients with MIS-C who had not received IVIG. However, Troponin C2 and KLHL12 autoantibodies were detected in 2 of 20 and 1 of 20 patients with MIS-C, respectively. Overall, these results suggest that IVIG therapy may be a confounding factor in autoantibody measurements in MIS-C and that antibodies against antigens associated with autoimmune diseases or other human proteins are uncommon in MIS-C.

BackgroundLefamulin, a first-in-class pleuromutilin antibiotic approved for intravenous and oral use in adults with community-acquired bacterial pneumonia (CABP), was noninferior to moxifloxacin in the Lefamulin Evaluation Against Pneumonia (LEAP) 1 intravenous-to-oral switch study and the LEAP 2 oral-only study. Using pooled LEAP 1/2 data, we examined lefamulin efficacy/safety overall and within subgroups of patients presenting with comorbidities typical in CABP management.MethodsIn LEAP 1, adults with CABP were randomized to receive intravenous lefamulin (150 mg every 12 h) for 5‒7 days or moxifloxacin (400 mg every 24 h) for 7 days, with optional intravenous-to-oral switch if predefined improvement criteria were met. In LEAP 2, adults with CABP were randomized to receive oral lefamulin (600 mg every 12 h) for 5 days or moxifloxacin (400 mg every 24 h) for 7 days. Both studies assessed early clinical response (ECR) at 96 ± 24 h after first study drug dose and investigator assessment of clinical response (IACR) at test-of-cure (5‒10 days after last dose). Pooled analyses of the overall population used a 10% noninferiority margin.ResultsLefamulin (n = 646) was noninferior to moxifloxacin (n = 643) for ECR (89.3% vs 90.5%, respectively; difference  - 1.1%; 95% CI  - 4.4 to 2.2); IACR success rates at test-of-cure were similarly high (≥ 85.0%). High efficacy with both lefamulin and moxifloxacin was also demonstrated across all well-represented patient subgroups, including those with advanced age, diabetes mellitus, a history of cardiovascular diseases (e.g., hypertension, congestive heart failure, or arrhythmia) or chronic lung diseases (e.g., asthma or chronic obstructive pulmonary disease), elevated liver enzymes, or mild-to-moderate renal dysfunction. No new safety signals were identified.ConclusionsLefamulin may provide a valuable intravenous/oral monotherapy alternative to fluoroquinolones or macrolides for empiric treatment of patients with CABP, including cases of patients at risk for poor outcomes due to age or various comorbidities.Trial registrationClinicalTrials.gov LEAP 1 (NCT02559310; Registration Date: 24/09/2015) and LEAP 2 (NCT02813694; Registration Date: 27/06/2016).

BackgroundUnderstanding the reasons for loss to follow-up (LTFU) in cohort studies, especially among marginalized groups such as people who inject drugs (PWID), is needed to strengthen the rigor of efficacy trials for prevention and treatment interventions. We assessed the proportion and reasons for loss to follow-up in a recent cohort of PWID enrolled in the southeast of Iran.MethodsUsing respondent-driven sampling, we recruited 98 PWID age 18 years or older who reported injecting drugs in the past 6 months, and were negative for HIV and HCV at initial screening. Participants were followed at 6 week intervals, alternating a short six-week visit and long 12-week or quarterly visit to measure incidence of HIV and HCV. Methods to enhance retention included incentives for completing each visit, tracking people who missed the scheduled visits through their peer referral networks, engaged outreach teams to explore hotspots and residences, and photos. LTFU was defined as participants who missed their quarterly visits for two or more weeks.ResultsMean (SD) age of participants was 39.7 years (SD 9.6). Of 98 enrolled, 50 participants (51.0%) were LTFU by missed their scheduled quarterly visits for 2 weeks or more. For those whose reasons for LTFU could be defined (46.0%, 23 of 50), main reasons were: forgetting the date of visit (43.5%, 10 of 23), being incarcerated (39.1%, 9 of 23), and moving out of the city (17.4%, 4 of 23).ConclusionThis study highlighted the difficulty in retaining PWID in longitudinal studies. Despite having several retention strategies in place, over half of PWID were LTFU. The LTFU might be reduced by setting up more effective reminder systems, working closely with security systems, and online means to reach those who move outside the study area.

BackgroundStreet-based female sex workers (FSWs) are highly at risk of HIV and other harms associated with sex work. We assessed the prevalence of non-injection and injection drug use and their associated factors among street-based FSWs in Iran.MethodsWe recruited 898 FSWs from 414 venues across 19 major cities in Iran between October 2016 and March 2017. Correlates of lifetime and past-month non-injection and injection drug use were assessed through multivariable logistic regression models. Adjusted odds ratios (AOR) and 95% confidence intervals (CI) were reported.ResultsLifetime and past-month non-injection drug use were reported by 60.3% (95% CI 51, 84) and 47.2% (95% CI 38, 67) of FSWs, respectively. The prevalence of lifetime and past-month injection drug use were 8.6% (95% CI 6.9, 10.7) and 3.7% (95% CI 2.6, 5.2), respectively. Recent non-injection drug use was associated with divorced marital status (AOR 2.00, 95% CI 1.07, 3.74), temporary marriage (AOR 4.31 [1.79, 10.40]), had > 30 clients per month (AOR 2.76 [1.29, 5.90]), ever alcohol use (AOR 3.03 [1.92, 6.79]), and history of incarceration (AOR 7.65 [3.89, 15.30]). Similarly, lifetime injection drug use was associated with ever alcohol use (AOR 2.74 [1.20-6.20]), ever incarceration (AOR 5.06 [2.48-10.28]), and ever group sex (AOR 2.44 [1.21-4.92]).ConclusionsNon-injection and injection drug use are prevalent among street-based FSWs in Iran. Further prevention programs are needed to address and reduce harms associated with drug use among this vulnerable population in Iran.

BackgroundFor over 30 years, syringe services programs (SSPs) have served as an efficacious intervention for the prevention of HIV and Hepatitis C transmission among persons who use drugs. Despite a strong body of evidence for the effectiveness of SSPs as a preventative public health measure, numerous local and state governments in the United States continue to resist the establishment of new SSPs and aggressively pursue the closure of those already in operation.CommentaryIn Orange County, California, local officials have repeatedly mobilized in opposition of the establishment of syringe access - thereby hindering access to healthcare for thousands of predominantly unhoused individuals. The county was previously served by the Orange County Needle Exchange Program from 2016 until 2018 when a civil suit brought by the Orange County Board of Supervisors resulted in the closure of the program. For more than 2 years, persons who inject drugs in Orange County lacked reliable access to clean syringes, placing them at increased risk for contracting HIV and Hepatitis C. Here, we comment on the ongoing effort to restore syringe access in Orange County. This collaborative physician-directed endeavor has brought together students and community volunteers to provide vital harm reduction services to a remarkably underserved population. Since the reestablishment of syringe access in Orange County by the Harm Reduction Institute, new legal barriers have arisen including the passage of new municipal legislation banning the operation of syringe exchanges. We are well-equipped to overcome these obstacles. This work serves as an affirmation of assertions made by previous authors regarding the unique qualifications of medical & graduate students as effective harm reductionists.ConclusionHarm reduction services are vital to the health and well-being of people who use drugs. The provision of these services should not be impeded by legislative interference by municipal, county, or state governments.

BackgroundDrug use is a growing concern in Ghana. People who inject drugs (PWID) are highly vulnerable to HIV and other infectious diseases. Ghana's National Strategic Plan for HIV/AIDS 2016-2020 identifies PWID as a key population, but efforts to address the needs of PWID have lagged behind those targeting sex workers and men who have sex with men. Lack of information about PWID is a critical barrier to implementing effective HIV prevention and treatment. We aimed to learn more about the vulnerability of the PWID population in order to inform much-needed harm reduction interventions.MethodsFrom April to July 2018, we conducted a mixed methods study in Kumasi, Ghana, to identify all major drug using locations, count the numbers of PWID to obtain rough population size estimations, and administer anonymous surveys to 221 PWID regarding drug use and sexual behavior. We also tested for HIV, HCV, and HBV from syringes used by survey participants.ResultsKey informants identified five major drug using locations and estimated the total PWID population size to be between 600 and 2000. Enumerators counted between 35 and 61 individuals present at each of the five bases. Sharing syringes and reusing discarded syringes are common practices. Over half of survey participants (59%) reported past-month syringe sharing (34% used a used syringe and 52% gave away a used syringe). Individuals with higher injection frequency (≥ 21 times weekly) and who injected with four or more people had higher odds of syringe sharing. Of the survey participants reporting sex in the last month (23%), most reported having one partner, but only 12% used condoms. Nearly all women (11/13) reported exchanging sex for drugs and 6/13 reported exchanging sex for money in the last six months. Fifteen percent of participants (all men) reported paying for sex using drugs or money. Of the used syringes, prevalence estimates were 3% (HIV), 2% (HCV), and 9% (HBV).ConclusionsOur findings confirm the urgent need to implement harm reduction interventions targeting PWID and to build a strong and enabling legal and policy environment in Ghana to support these efforts.

BackgroundThere is little information regarding the safety of intravenous tissue plasminogen activator (IV-tPA) in patients with stroke and COVID-19.MethodsThis multicenter study included consecutive stroke patients with and without COVID-19 treated with IV-tPA between February 18, 2019, to December 31, 2020, at 9 centers participating in the CASCADE initiative. Clinical outcomes included modified Rankin Scale (mRS) at hospital discharge, in-hospital mortality, the rate of hemorrhagic transformation. Using Bayesian multiple regression and after adjusting for variables with significant value in univariable analysis, we reported the posterior adjusted odds ratio (OR, with 95% Credible Intervals [CrI]) of the main outcomes.ResultsA total of 545 stroke patients, including 101 patients with COVID-19 were evaluated. Patients with COVID-19 had a more severe stroke at admission. In the study cohort, 85 (15.9%) patients had a hemorrhagic transformation, and 72 (13.1%) died in the hospital. After adjustment for confounding variables, discharge mRS score ≥2 (OR: 0.73, 95% CrI: 0.16, 3.05), in-hospital mortality (OR: 2.06, 95% CrI: 0.76, 5.53), and hemorrhagic transformation (OR: 1.514, 95% CrI: 0.66, 3.31) were similar in COVID-19 and non COVID-19 patients. High-sensitivity C reactive protein level was a predictor of hemorrhagic transformation in all cases (OR:1.01, 95%CI: 1.0026, 1.018), including those with COVID-19 (OR:1.024, 95%CI:1.002, 1.054).ConclusionIV-tPA treatment in patients with acute ischemic stroke and COVID-19 was not associated with an increased risk of disability, mortality, and hemorrhagic transformation compared to those without COVID-19. IV-tPA should continue to be considered as the standard of care in patients with hyper acute stroke and COVID-19.

BackgroundPolice constitute a structural determinant of health and HIV risk of people who inject drugs (PWID), and negative encounters with law enforcement present significant barriers to PWID access to harm reduction services. Conversely, police may facilitate access via officer-led referrals, potentiating prevention of HIV, overdose, and drug-related harms. We aimed to identify police characteristics associated with support for officer-led referrals to addiction treatment services and syringe service programs (SSP). We hypothesized that officers who believe harm reduction services are contradictory to policing priorities in terms of safety and crime reduction will be less likely to support police referrals.MethodsBetween January and June 2018, police officers (n = 305) in Tijuana, Mexico, completed self-administered surveys about referrals to harm reduction services during the 24-month follow-up visit as part of the SHIELD police training and longitudinal cohort study. Log-binomial regression was used to estimate adjusted prevalence ratios and model policing characteristics and attitudes related to officers' support for including addiction treatment and SSP in referrals.ResultsRespondents were primarily male (89%), patrol officers (86%) with a median age of 38 years (IQR 33-43). Overall, 89% endorsed referral to addiction services, whereas 53% endorsed SSP as acceptable targets of referrals. Officers endorsing addiction services were less likely to be assigned to high drug use districts (adjusted prevalence ratio [APR] = 0.50, 95% CI 0.24, 1.08) and more likely to agree that methadone programs reduce crime (APR = 4.66, 95% CI 2.05, 9.18) than officers who did not support addiction services. Officers endorsing SSPs were younger (adjusted prevalence ratio [APR] = 0.96 95% CI 0.93, 0.98), less likely to be assigned to high drug use districts (APR = 0.50, 95% CI 0.29, 0.87), more likely to believe that methadone programs reduce crime (APR = 2.43, 95% CI 1.30, 4.55), and less likely to believe that SSPs increase risk of needlestick injury for police (APR = 0.44, 0.27, 0.71).ConclusionsBeliefs related to the occupational impact of harm reduction services in terms of officer safety and crime reduction are associated with support for referral to related harm reduction services. Efforts to deflect PWID from carceral systems toward harm reduction by frontline police should include measures to improve officer knowledge and attitudes about harm reduction services as they relate to occupational safety and law enforcement priorities.Trial registrationNCT02444403.

A summary of intravenous Non-Steroidal Anti-inflammatory Agents (NSAIDs) is presented with mode of action, potential complications, and therapeutic indications reviewed. Their role in a multimodal analgesic regimen for ambulatory surgery is also discussed. [ABSTRACT FROM AUTHOR]

Menbutone is a choleretic agent currently used in Europe to treat digestive disorders in livestock and dogs. Pharmacokinetic parameters were established in 4-month Holstein calves after intravenous (IV) and intramuscular (IM) administration. The drug was administered to 12 animals (10 mg/kg) for both IV and IM routes following a crossover design. Plasma samples were collected at various time points over 24 h and analyzed by reverse-phase high-performance liquid chromatography with a photodiode-array detector, following a method validated according to European Medicines Agency guidelines. Pharmacokinetic parameters were calculated using compartmental and non-compartmental methods. Menbutone followed a two-compartment open model after IV injection, with a total clearance (Cl) of 71.9 ± 13.5 mL/h/kg, an elimination half-life (t½β) of 4.53 ± 2.45 h, and a volume of distribution at steady-state (Vss) of 310.4 ± 106.4 mL/kg. Non-compartmental elimination half-life (t½λ) was 4.2 ± 1.1 h. After IM administration, drug pharmacokinetics was best described by a one-compartment open model. The peak plasma concentration (Cmax) was 15.1 ± 4.3 µg/mL; the time to reach Cmax (tmax), 1.66 ± 0.55 h; and the mean absorption time (MAT), 2.50 ± 1.42 h. Absorption was high, with a fraction of the dose absorbed (F) of 83.5 ± 22.4%. Menbutone was rapidly eliminated from plasma for both routes of administration, with a fast and high IM bioavailability.

BACKGROUND: Children often develop phobia toward needle pricks and invasive procedures. It is difficult for medical personnel to manage children’s pain when they are in the hospital. When it comes to assessing and treating children’s discomfort, nurses interact with them the most. The main objective of the study was to evaluate the effectiveness of the Buzzy Bee device on pain perception among children undergoing invasive needle pricks as part of their treatment. MATERIALS AND METHODS: The study used a quantitative approach with a quasi-experimental design employing simple random sampling. A post-test-only design was used. After obtaining ethical clearance, data collection was done in the pediatric outpatient department and pediatric wards of Sultan Qaboos University Hospital, Muscat, Oman, between February 2020 and August 2021. Faces Pain Rating Scale for children was used to rate the pain during the procedure, which is a standardized tool. Data were analyzed using SPSS version 23. Descriptive and inferential statistical tests were done to analyze the data. RESULTS: Totally, 120 children along with their parents were interested in the study. After taking appropriate parental consent and children’s assent, the participants were recruited by simple random sampling. They were equally divided into 60 in the experimental group and 60 in the control group. The mean age was 8.14 (+/-2.3) in both groups. Among the 120 samples, 63 (52.5%) of them were males and 57 (47.5%) were females. The majority of them had diagnoses like thalassemia, leukemia, and sickle cell and were getting cannulated for blood transfusion therapy. t-test shows that 51.7% (31 samples) reported no pain in the experimental group and 33.3% (20 samples) reported only mild pain, whereas in the control group, only 5.0% (3 samples) reported no pain and 21.7% (13 samples) reported mild pain. About 26.7% of the samples reported very much pain as against the 7% who reported very much pain in the interventional group. There was a statistically significant difference in the pain scores between the control group and the experimental group (likelihood ratio test, P = 0.0001). The Buzzy Bee method significantly reduced the pain. CONCLUSION: The introduction of a toy-like, child-friendly device, which works on the mechanism of vibrations and cold application, lessened the pain intensity during the procedure and acted as a good distractive therapy for children.

Occasionally intravenous insertion forms a challenge to a number of patients. Inserting an IV needle is a difficult task that requires a lot of skill. At the moment, only doctors and medical personnel are allowed to do this because it requires finding the right vein, inserting the needle properly, and carefully injecting fluids or drawing out blood. Even for trained professionals, this can be done incorrectly, which can cause bleeding, infection, or damage to the vein. It is especially difficult to do this on children, elderly people, and people with certain skin conditions. In these cases, the veins are harder to see, so it is less likely to be done correctly the first time and may cause blood clots. In this research, a low-cost embedded system utilizing Near-Infrared (NIR) light technology is developed, and two novel approaches are proposed to detect and select the best candidate veins. The two approaches utilize multiple computer vision tools and are based on contrast-limited adaptive histogram equalization (CLAHE). The accuracy of the proposed algorithm is 91.3% with an average 1.4 s processing time on Raspberry Pi 4 Model B.

Background and Objectives: The impact of anesthetic agents on memory and cognitive function following general anesthesia is of great interest, particularly regarding their effects on the developing pediatric brain. While numerous studies have examined the relationship between anesthetic drugs and brain function, research focusing on early cognitive function following sedation remains limited. Materials and Methods: This study was a prospective, randomized controlled trial involving 148 pediatric patients scheduled for hematological procedures, specifically bone marrow aspiration (BMA) and intrathecal chemotherapy (ITC). Patients were divided into two groups based on the primary anesthetic used: the inhalational sedation group (IHG), in which sevoflurane was used, and the intravenous sedation group (IVG), which received propofol infusion. Apart from the main anesthetic agent, all sedation methods were consistent across both groups. A cognitive function test administered before sedation involved memorizing four distinct images, each associated with a different number. Then, the patients were asked to identify the omitted image upon awakening in the recovery room. Herein, this pre- vs. post-sedation test is called the early recognition assessment (ERA) tool. The primary outcome was the correct response rate after sedation for the two groups. Secondary outcomes included the sedation score, the behavior response score, and the correct response rates according to the number of sedation procedures. Results: This study included 130 patients in the final analysis, with 74 originally assigned to each group. The initial cognitive assessment revealed no significant difference in performance between the anesthetic agents. In addition, no differences were observed in the rates of correct responses or post-sedation scores after repeated procedures. However, the IVG demonstrated higher behavior response scores compared to the IHG. Conclusions: There were no significant differences in the rates of correct responses using the ERA tool between the two groups, irrespective of the number of sedation procedures performed. While some differences were noted in preoperative, intraoperative, and post-anesthesia care, these did not significantly impact the cognitive outcomes measured.

(1) Background: We aim to examine and improve phosphate prescribing as part of a quality assurance program by examining the change in the proportion of patients receiving phosphate with normal or high preceding serum phosphate concentrations before and after the introduction of the 24 h time limit to default phosphate prescription. (2) Methods: This was a quality assurance study conducted across three Australian adult intensive care units (ICUs). All adult patients with ICU lengths of stay greater than or equal to 48 h who had their serum phosphate concentrations measured were included. A 24 h time limit was introduced to the protocolised prescription in the electronic clinical information system for enteral and intravenous phosphate at participating ICUs. Patient characteristics, phosphate administration, and outcomes were compared before and after this time limit was introduced. The primary outcome was the proportion of patients to whom phosphate was prescribed after measurement of a normal or high serum phosphate level. Secondary outcomes were ICU length of stay, mortality, and discharge destination. (3) Results: A total of 1192 patients were included from three ICUs over the two periods. The proportion of patients with a normal or high measured phosphate level who then received phosphate supplementation was significantly lower in the second study period (30.3% vs. 9.9%; p < 0.001). This difference persisted when adjusted for potential confounders in a mixed-effects logistic regression model (an adjusted odds ratio for receiving phosphate with normal or high serum concentration 0.214, 95% confidence interval of 0.132–0.347; p < 0.001). No significant difference was seen in the typical ICU length of stay, in-hospital case–fatality rate, and hospital discharge destination between these groups. (4) Conclusions: This multicentre before–after study has demonstrated that the introduction of a 24 h limit on electronic phosphate prescriptions resulted in significantly fewer patients receiving phosphate when their serum phosphate concentration was normal or high, without any adverse impact on patient outcomes.

BackgroundEarly administration of convalescent plasma obtained from blood donors who have recovered from coronavirus disease 2019 (Covid-19) may prevent disease progression in acutely ill, high-risk patients with Covid-19.MethodsIn this randomized, multicenter, single-blind trial, we assigned patients who were being treated in an emergency department for Covid-19 symptoms to receive either one unit of convalescent plasma with a high titer of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or placebo. All the patients were either 50 years of age or older or had one or more risk factors for disease progression. In addition, all the patients presented to the emergency department within 7 days after symptom onset and were in stable condition for outpatient management. The primary outcome was disease progression within 15 days after randomization, which was a composite of hospital admission for any reason, seeking emergency or urgent care, or death without hospitalization. Secondary outcomes included the worst severity of illness on an 8-category ordinal scale, hospital-free days within 30 days after randomization, and death from any cause.ResultsA total of 511 patients were enrolled in the trial (257 in the convalescent-plasma group and 254 in the placebo group). The median age of the patients was 54 years; the median symptom duration was 4 days. In the donor plasma samples, the median titer of SARS-CoV-2 neutralizing antibodies was 1:641. Disease progression occurred in 77 patients (30.0%) in the convalescent-plasma group and in 81 patients (31.9%) in the placebo group (risk difference, 1.9 percentage points; 95% credible interval, -6.0 to 9.8; posterior probability of superiority of convalescent plasma, 0.68). Five patients in the plasma group and 1 patient in the placebo group died. Outcomes regarding worst illness severity and hospital-free days were similar in the two groups.ConclusionsThe administration of Covid-19 convalescent plasma to high-risk outpatients within 1 week after the onset of symptoms of Covid-19 did not prevent disease progression. (SIREN-C3PO ClinicalTrials.gov number, NCT04355767.).

ContextSupervised injection facilities are harm reduction interventions that allow people who inject drugs to use previously obtained substances under the supervision of health professionals. Although currently considered illegal under U.S. federal law, several U.S. cities are considering implementing supervised injection facilities anyway as a response to the escalating overdose crisis. The objective of this review is to determine the effectiveness of supervised injection facilities, compared with that of control conditions, for harm reduction and community outcomes.Evidence acquisitionStudies were identified from 2 sources: a high-quality, broader review examining supervised injection facility-induced benefits and harms (from database inception to January 2014) and an updated search using the same search strategy (January 2014‒September 2019). Systematic review methods developed by the Guide to Community Preventive Services were used (screening and analysis, September 2019‒December 2020).Evidence synthesisA total of 22 studies were included in this review: 16 focused on 1 supervised injection facility in Vancouver, Canada. Quantitative synthesis was not conducted given inconsistent outcome measurement across the studies. Supervised injection facilities in the included studies (n=number of studies per outcome category) were mostly associated with significant reductions in opioid overdose morbidity and mortality (n=5), significant improvements in injection behaviors and harm reduction (n=7), significant improvements in access to addiction treatment programs (n=7), and no increase or reductions in crime and public nuisance (n=7).ConclusionsFor people who inject drugs, supervised injection facilities may reduce the risk of overdose morbidity and mortality and improve access to care while not increasing crime or public nuisance to the surrounding community.

IntroductionAmong people who inject drugs (PWID), polysubstance use has been associated with fatal and non-fatal overdose (NFOD). However, the risk of overdose due to the cumulative number of various recently used drug types remains unexplored. We estimated the risk of NFOD for different polysubstance use categories among PWID in Tijuana, Mexico.MethodsData came from 661 participants followed for 2 years in Proyecto El Cuete-IV, an ongoing prospective cohort of PWID. A multivariable Cox model was used to assess the cumulative impact of polysubstance use on the time to NFOD. We used the Cochran-Armitage test to evaluate a dose-response relationship between number of polysubstance use categories and NFOD.ResultsWe observed 115 NFOD among 1029.2 person-years of follow-up (incidence rate: 11.2 per 100 person-years; 95% confidence interval [CI] 9.3-13.3). Relative to those who used one drug class, the adjusted hazard ratio of NFOD for individuals reporting using two drug classes was 1.11 (95% CI 0.69-1.79), three drug classes was 2.00 (95% CI 1.16-3.44) and for those reporting three compared to two was 1.79 (95% CI 1.09-2.97). A significant Cochran-Armitage trend test (P