Improving translation of animal models of addiction and relapse by reverse translation.

Critical features of human addiction are increasingly being incorporated into complementary animal models, including escalation of drug intake, punished drug seeking and taking, intermittent drug access, choice between drug and non-drug rewards, and assessment of individual differences based on criteria in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Combined with new technologies, these models advanced our understanding of brain mechanisms of drug self-administration and relapse, but these mechanistic gains have not led to improvements in addiction treatment. This problem is not unique to addiction neuroscience, but it is an increasing source of disappointment and calls to regroup. Here we first summarize behavioural and neurobiological results from the animal models mentioned above. We then propose a reverse translational approach, whose goal is to develop models that mimic successful treatments: opioid agonist maintenance, contingency management and the community-reinforcement approach. These reverse-translated 'treatments' may provide an ecologically relevant platform from which to discover new circuits, test new medications and improve translation.

Public Acceptance of Measures to Control Infectious Diseases Under Different Scenarios of Severity and Transmissibility.

OBJECTIVES: Public health measures to control future epidemic threats of contagious disease, such as new variants of COVID-19, may be usefully informed by evidence about how acceptable they are likely to be, and the circumstances that condition this acceptance. This study considers how the acceptability of nonpharmaceutical interventions (NPIs) might depend on scenarios about the severity and transmissibility of the disease. METHODS: A telephone survey was conducted among a representative cross-sectional sample of the Spanish adult population. Each respondent was randomly assigned to 1 of 4 possible hypothetical scenarios about the severity and transmissibility of the disease. Participants' responses about the acceptability of 11 NPI under this scenario were analyzed using multivariate regression and latent class cluster analysis. RESULTS: A high risk of severe disease increases the acceptability of mask wearing, social distancing outdoors, lockdown, and isolation of infected cases, close contacts, and the vulnerable. A scenario in which the disease is highly transmissible would increase the acceptability of NPI that restrict movement and isolation. Most respondents would broadly accept most NPI in situations when either the severity or transmissibility was high. CONCLUSIONS: This study showed that people are more willing to accept NPIs such as mask wearing, social distancing outdoors, lockdown, and isolation in severe disease scenarios. A highly transmissible disease scenario increases the acceptability of NPIs that isolate. A majority would broadly accept NPIs to counter public health emergencies, whereas 3% to 9% of the population would always be strongly against.

Objective Neighborhood-Level Disorder Versus Subjective Safety as Predictors of HIV Transmission Risk and Momentary Well-Being.

Mental health and HIV risk behavior have been studied with ecological momentary assessment (EMA), but this approach has not been combined with tracking of activity space (where people go and what they encounter there) in people with HIV and their social relations, who may be HIV+ or HIV-. Activity space represents a modifiable risk or protective factor for behavior related to health status and quality of life, in both clinical and nonclinical populations. We conducted an observational study with 286 participants (243 HIV+ and 43 HIV-), roughly matched for socioeconomic status and neighborhood of residence via three waves of snowball sampling. Each participant carried a smartphone for up to 4 weeks, making 5 randomly prompted entries and 1 end-of-day entry each day, plus self-initiated event-contingent entries for sexual activity and drug use. Responses to randomly prompted items provided subjective evaluations of the safety of the participant's current social and physical environment (the place they were and the people they were with). GPS-based location tracking-coupled with publicly available statistic indicating neighborhood-level physical disorder and socioeconomic disadvantage-provided an indicator of each participant's exposure to objective psychosocial hazard. We examined possible relationships of these objective and subjective environmental exposures with risky sexual and intravenous drug-use behavior, knowledge and utilization of antiretroviral treatment and prophylaxis, and momentary mental health (mood and stress, which relate to risky behavior and overall well-being). We found that both risky behavior and mental health were more related to participants' subjective evaluations of their activity space than to objective measures of neighborhood-level disorder, suggesting that, even within an objectively hazardous neighborhood, people who find a niche they perceive as socially and physically safe may engage in less risky behavior and have better well-being.Trial registration Clinicaltrials.gov Identifier NCT01571752.

RETINAL VEIN OCCLUSIONS BEFORE AND DURING THE COVID-19 PANDEMIC: Visual Outcomes and Treatment Patterns in a Country with no Mandatory Lockdown.

PURPOSE: To investigate the incidence, treatment patterns, and visual outcomes in patients with branch retinal vein occlusion (RVO) and central RVO before and during the COVID-19 pandemic in a country with no mandatory lockdown. METHODS: This retrospective study included 788 patients presenting with a RVO during the years 2019 to 2022 at St. Erik Eye Hospital. The control group and study groups consisted of patients presenting before and during the pandemic, respectively. RESULTS: The incidence of diagnosed RVO cases decreased from 281 patients before the pandemic to 236 patients during the first year of the pandemic ( P < 0.05). In patients with branch RVO at the end of follow-up, the best-corrected visual acuity improved 10.3 letters (95% confidence intervals [CI] 7.6-12.9) in the control group compared with 14.3 letters (95% CI 12.6-16.0) in the study groups ( P < 0.05). In patients with central RVO, the best-corrected visual acuity improved 6.3 letters (95% CI 2.7-10.0) in the control group compared with 8.6 letters (95% CI 5.7-11.4) in the study groups (p = NS). Overall, the number of intravitreal anti-vascular endothelial growth factor injections increased from 7.0 (95% CI 6.6-7.3) in the control group to 7.6 (95% CI 7.4-7.8) in the study groups ( P < 0.05). CONCLUSION: Good visual and anatomical outcomes were sustained, and the number of intravitreal anti-vascular endothelial growth factor injections increased significantly in patients with RVO during the COVID-19 pandemic.

The Protective Effect of Social Reward on Opioid and Psychostimulant Reward and Relapse: Behavior, Pharmacology, and Brain Regions.

Until recently, most modern neuroscience research on addiction using animal models did not incorporate manipulations of social factors. Social factors play a critical role in human addiction: social isolation and exclusion can promote drug use and relapse, while social connections and inclusion tend to be protective. Here, we discuss the state of the literature on social factors in animal models of opioid and psychostimulant preference, self-administration, and relapse. We first summarize results from rodent studies on behavioral, pharmacological, and circuit mechanisms of the protective effect of traditional experimenter-controlled social interaction procedures on opioid and psychostimulant conditioned place preference, self-administration, and relapse. Next, we summarize behavioral and brain-mechanism results from studies using newer operant social-interaction procedures that inhibit opioid and psychostimulant self-administration and relapse. We conclude by discussing how the reviewed studies point to future directions for the addiction field and other neuroscience and psychiatric fields, and their implications for mechanistic understanding of addiction and development of new treatments.SIGNIFICANCE STATEMENT In this review, we propose that incorporating social factors into modern neuroscience research on addiction could improve mechanistic accounts of addiction and help close gaps in translating discovery to treatment. We first summarize rodent studies on behavioral, pharmacological, and circuit mechanisms of the protective effect of both traditional experimenter-controlled and newer operant social-interaction procedures. We then discuss potential future directions and clinical implications.

Cost-effectiveness of Diagnostic Tools to Establish the Presence of Peripheral Arterial Disease in People With Diabetes.

OBJECTIVE: To evaluate the cost-effectiveness of point-of-care duplex ultrasound (PAD-scan) and other bedside tests for the diagnosis of peripheral arterial disease (PAD) in people with diabetes. BACKGROUND: PAD is a risk factor for cardiovascular disease, diabetic foot ulceration (DFU), and amputation in diabetic patients. Diagnosis enables optimization of therapies to manage these risks. PAD-scan can be performed by frontline staff and has been shown to be the most accurate bedside test. However, its cost-effectiveness has not been investigated. METHODS: A Markov model was constructed to estimate the health outcomes and costs over 5 years of different testing strategies applied to a cohort of diabetic patients. Bedside tests investigated were PAD-scan, ankle-brachial pressure index, toe-brachial pressure index, audible and visual Doppler, transcutaneous pressure of oxygen, and pulse palpation. Health outcomes were incidence of new DFU, major cardiovascular events, amputation, death, and DFU healing rates. Sensitivity analyses were performed. RESULTS: PAD-scan was the most cost-effective bedside test with an incremental cost-effectiveness ratio of £11,391/quality-adjusted life years. PADscan had the highest probability (78.7%) of having the greatest net benefit at a willingness to pay threshold of £20,000 per quality-adjusted life years. It reduced the number of amputations by 24% and the number of cardiovascular deaths by 10% over 5 years, compared to toe-brachial pressure index (next best alternative). PAD-scans superiority in incremental cost-effectiveness ratio occurred at a PAD prevalence threshold of 0.24. DISCUSSION: PAD-scan is a cost-effective test for the detection of PAD in patients with diabetes.

Noninfectious causes of fever in hematologic malignancies. Are antibiotics still indicated?

PURPOSE OF REVIEW: Fever is a common manifestation of both infectious and noninfectious processes in recipients of hematopoietic cell transplantation (HCT) and chimeric antigen receptor T-cell (CAR-T) therapy. Understanding the diverse causes of fever in these settings allows for accurate diagnosis and optimal use of antibiotics. RECENT FINDINGS: Herein we review common noninfectious syndromes seen in HCT and CAR-T recipients and discuss best practices in the management of these complex clinical scenarios regarding diagnosis and antibiotic use. In recent years, adverse effects of antimicrobials have highlighted the importance of antimicrobial stewardship in HCT and CAR-T patients, and an antibiotic de-escalation strategy is a safe and important tool in mitigating these adverse events, even in patients with ongoing neutropenia who become afebrile without a known infection. Common adverse events associated with antibiotics include an increased risk of Clostridiodes difficile infection (CDI), a higher incidence of multidrug-resistant organisms (MDROs), and microbiome dysbiosis. SUMMARY: Clinicians should be aware of noninfectious causes of fever in these immunocompromised patients and utilize best antibiotic practices while managing these patients.

Cost-effectiveness of carotid endarterectomy in symptomatic patients.

BACKGROUND: Medical therapy for stroke prevention has improved significantly over the past 30 years. Recent analyses of medically treated cohorts have suggested that early rates of stroke may have reduced, and reports of the safety of carotid surgery have also shown improvements. Since the effectiveness of carotid surgery versus medical therapy was established in the 1990s, there is an urgent need to evaluate whether surgery remains cost-effective in the UK. METHODS: A decision model was developed to estimate the lifetime costs and utilities of modern medical therapy with and without carotid endarterectomy in patients with symptomatic stenosis from the perspective of the UK National Health Service. The base-case population consisted of adults aged 70 years with 70-99 per cent stenosis. Model data were obtained from clinical studies and wider literature. Univariate and probabilistic sensitivity analyses were carried out. RESULTS: In the base-case scenario, the 5-year absolute risk reduction with carotid endarterectomy was 5 per cent, and the incremental cost-effectiveness ratio was €12 021 (exchange rate £1 GBP = €1.1125 (Tuesday 1 January 2019)) per quality-adjusted life-year. Surgery was more cost-effective if performed rapidly after presentation. In patients with 50-69 per cent carotid stenosis, surgery appeared less clinically effective. However, there was considerable uncertainty. CONCLUSION: Surgery may not now be clinically effective and cost-effective in those with moderate carotid stenosis. However, these results are uncertain because of the limited data on modern medical therapy and an RCT may be justified.

Challenges for Economic Evaluations of Advanced Therapy Medicinal Products: A Systematic Review.

OBJECTIVES: Advanced therapy medicinal products (ATMPs) are drugs for human use for the treatment of chronic, degenerative, or life-threatening diseases that are based on genes, tissues, or cells. This article aimed to identify and critically review published economic analyses of ATMPs. METHODS: A systematic review of economic analyses of ATMPs was undertaken. Study characteristics, design, sources of data, resources and unit costs, modeling and extrapolation methods, study results, and sensitivity analyses were assessed. RESULTS: A total of 46 economic analyses of ATMP (from 45 articles) were included; 4 were cell therapy medicinal products, 33 gene therapy medicinal products, and 9 tissue-engineered products. 30 therapies had commercial marketing approval; 39 studies were cost-utility analysis, 5 were cost-effectiveness analysis, and 2 were cost only studies. Four studies predicted that the ATMP offered a step change in the management of the condition and 10 studies estimated that the ATMP would offer a lower mean cost. CONCLUSIONS: Comparison with historical controls, pooling of data, and use of techniques such as mixture cure fraction models should be used cautiously. Sensitivity analyses should be used across a plausible range of prices. Clinical studies need to be designed to align with health technology assessment requirements, including generic quality of life, and payers should aim for clarity of criteria. Regulators and national payers should aim for compatibility of registers to allow interchange of data. Given the increasing reliance on industry-funded economic analyses, careful critical review is recommended.

INES: Interactive tool for construction and extrapolation of partitioned survival models.

BACKGROUND: INES (INteractive model for Extrapolation of Survival and cost) provides an open-access tool powered by R that implements three-state partitioned survival models (PSM). This article describes the properties of the tool, and the situations where INES may or may not be suitable. METHODS: INES is designed to be used by investigators or healthcare professionals who have a good grasp of the principles of economic evaluation and understand the strengths and weaknesses of partitioned survival models, but are not sufficiently familiar with a statistical package such as Excel or R to be able to construct and test a de-novo PSM themselves. INES is delivered to the user via a batch file. Once downloaded to the user's hard drive, it interacts with the user via a portable version of R with web interactivity built in Shiny. INES requires absolutely no knowledge of R and the user does not need to have R or any of its dependences installed. Hence the user will deal with a standalone Shiny app. Inputs (digitalized survival curves, unit costs, posology, hazard ratios, discount rate) can be uploaded from a template spreadsheet. RESULTS: The INES application provides a seamlessly integrated package for estimating a set of parametric hazard functions for progression free and overall survival, selecting an appropriate function from this menu, and applying this as an input to a PSM to calculate mean costs and quality-adjusted life years. Examples are given that may serve as a tutorial. CONCLUSION: INES offers a rapid, flexible, robust and transparent tool for parametric survival analysis and calculating a PSM that can be used in many different contexts.

A tumor-associated splice-isoform of MAP2K7 drives dedifferentiation in MBNL1-low cancers via JNK activation.

Master splicing regulator MBNL1 shapes large transcriptomic changes that drive cellular differentiation during development. Here we demonstrate that MBNL1 is a suppressor of tumor dedifferentiation. We surveyed MBNL1 expression in matched tumor/normal pairs across The Cancer Genome Atlas and found that MBNL1 was down-regulated in several common cancers. Down-regulation of MBNL1 predicted poor overall survival in breast, lung, and stomach adenocarcinomas and increased relapse and distant metastasis in triple-negative breast cancer. Down-regulation of MBNL1 led to increased tumorigenic and stem/progenitor-like properties in vitro and in vivo. A discrete set of alternative splicing events (ASEs) are shared between MBNL1-low cancers and embryonic stem cells including a MAP2K7∆exon2 splice variant that leads to increased stem/progenitor-like properties via JNK activation. Accordingly, JNK inhibition is capable of reversing MAP2K7∆exon2-driven tumor dedifferentiation in MBNL1-low cancer cells. Our work elucidates an alternative-splicing mechanism that drives tumor dedifferentiation and identifies biomarkers that predict enhanced susceptibility to JNK inhibition.

Kava (Piper methysticum) in the United States: the quiet rise of a substance with often subtle effects.

Background: Piper methysticum, commonly called kava, has long been consumed in beverage form in the Pacific Islands. Kava use in the US has slowly increased since the 1990s, but is not assessed in major epidemiological surveys.Objectives: To analyze social-media posts about kava from current, past, and prospective users, for motivations, patterns of co-use, and effects.Methods: Text from Reddit posts, and accompanying metadata, were collected and thematically coded by two independent raters.Results: 423 posts were collected, spanning January 2006 through December 2021. Of the 1,211 thematic codes applied, 1,098 (90. 7%) were concordant. Motivations for use bifurcated into self-treatment (for psychiatric or physical health conditions) and recreation; these were not mutually exclusive. Kava was rarely considered strongly euphoriant, but was valued as an anxiolytic. Kava was frequently used with other substances, most commonly kratom. Kava was used at lower doses for self-treatment than for other purposes (pseudo-R2 = 0.11). Undesirable effects (gastrointestinal upset, fatigue) were mentioned, though less often than benefits. Hepatotoxicity, reported elsewhere as a rare, non-dose-related risk, was disputed on the basis of its not having been experienced by those posting.Conclusion: Kava appears to be conceptualized among Reddit posters as an anxiolytic with few risks or adverse effects. As it grows in popularity, especially among people who use other drugs that are more liable to misuse or addiction, it should be assessed in probability samples (i.e. in the major national drug surveys) and clinical practice for its risks, potential benefits, and possible drug-drug interactions.

Health Outcomes by Neighborhood (HON): Effects of Neighborhood, Social Instability, and Health Factors on 12-Month Trajectories of Substance-Use Disorder Symptoms.

BACKGROUND: Previous studies have shown that environment and health can influence drug use trajectories and the effects of substance use disorder (SUD) treatments. We hypothesized that trajectories of drug use-related problems, based on changes in DSM-5 symptoms, would vary by type(s) of drugs used, health factors, and neighborhood characteristics. METHODS: We assessed mental and physical health, stress, social instability, neighborhood characteristics (disorderliness and home value), and DSM-5 symptom counts at two study visits, 12 months apart, in a community sample (baseline N = 735) in Baltimore, MD. Three prominent categories of drug-use trajectory were identified with K-means cluster analysis of symptom counts: Persistent (4 or more symptoms at both visits or at Visit 2), Improved (decrease from 4 or more symptoms at Visit 1 to 3 or fewer symptoms at Visit 2), and Low-Stable (3 or fewer symptoms at both visits). Baseline health and neighborhood measures were tested as predictors of trajectory in mediation and moderation models. RESULTS: Among people with current opioid- and/or stimulant-use, odds of an Improved trajectory were (1) decreased with neighborhood disorder and social instability, or (2) increased with home value and social instability. Odds of a Low-Stable trajectory were decreased by social instability and stress but increased in those who were older or self-identified as white. CONCLUSIONS: Trajectories of drug use-related problems are influenced by sociodemographic variables, neighborhood factors, and health. Assessing DSM-5 symptom counts as an outcome measure may be valuable in monitoring or predicting long-term trajectories and treatment effectiveness.

Synthetic cartilage implant hemiarthroplasty versus cheilectomy for the treatment of hallux rigidus.

Degenerative arthritis of the first metatarsophalangeal joint, hallux rigidus, is the most common type of arthritis of the foot, affecting nearly 2.5% of the population over the age of 50. Hallux rigidus can be treated surgically with either Cheilectomy or Synthetic cartilage implant (SCI) hemiarthroplasty. The purpose of this study is to compare outcomes from a single institution on the treatment of hallux rigidus using cheilectomy and SCI hemiarthroplasty. Between 2012 and 2020, 49 patients underwent either a SCI (Polyvinyl alcohol hydrogels) hemiarthroplasty or Cheilectomy for the treatment of hallux rigidus. Functional scores were assessed pre and postoperatively using the American Orthopedic Foot and Ankle scoring System (AOFAS) and the Foot and Ankle Outcome Score survey (FAOS). Plantar and Dorsal range of motion was also assessed pre and postoperatively. Outcomes, complications, and any reoperations were recorded for all patients. Mean pre-op AOFAS for Cheilectomy and SCI were 49.6 and 54.8, respectively, compared to 85.3 and 89.7, respectively, after surgery (p value < 0.05). Mean pre-op Dorsal range of motion (ROM) for Cheilectomy and SCI were 24.0 and 26.0 degrees, respectively, compared to 38.0 and 42.6 degrees, respectively, after surgery (p value < 0.05). SCI hemiarthroplasty patients had higher AOFAS and dorsal ROM at the latest follow up (p value < 0.05). Synthetic cartilage implant (SCI) hemiarthroplasty and cheilectomy both offer promising results and remain viable treatment options to decrease pain, improve function, and maintain motion for hallux rigidus. SCI hemiarthroplasty may offer superior range of motion and functional outcomes than cheilectomy for hallux rigidus. LEVEL OF CLINICAL EVIDENCE: 3.

Accuracy of Pneumocystis jirovecii Plasma Cell-Free DNA PCR for Noninvasive Diagnosis of Pneumocystis Pneumonia.

Pneumocystis pneumonia (PCP) caused by Pneumocystis jirovecii is a serious infection in immunocompromised hosts which requires prompt diagnosis and treatment. The recommended specimen for diagnosis of PCP is bronchoalveolar lavage (BAL) fluid, which is invasive and may not be possible in unstable patients. The aim of this study was to evaluate the accuracy of noninvasive P. jirovecii plasma cell-free DNA (cfDNA) PCR using recently optimized preanalytical and analytical methods. Adult patients undergoing clinical testing for PCP with direct fluorescent antibody stain (DFA), respiratory PCR, and/or ß-d-glucan were included in this study. Sensitivity and specificity P. jirovecii plasma cfDNA PCR was determined in PCP suspects categorized as proven and probable. A total of 149 patients were included in this study, of which 10 had proven and 27 had probable PCP. Most patients (95.9%, 143/149) were immunocompromised, including hematological malignancies (30.1%), bone marrow transplant (11.2%), solid organ transplantation (47.6%), and HIV/AIDS (4.2%). P. jirovecii plasma cfDNA PCR showed sensitivity and specificity of 100% (10/10; 95% confidence interval [CI], 69.2 to 100) and 93.4% (127/136; 95% CI, 87.8 to 96.9), and 48.6% (18/37; 95% CI, 31.9 to 65.6) and 99.1% (108/109; 95% CI, 94.9 to 100) in proven and proven/probable cases, respectively. P. jirovecii cell-free DNA PCR was similar in sensitivity but with substantially improved specificity over ß-d-glucan (sensitivity, 60.0% [18/30; 95% CI, 40.6 to 77.3]); specificity, 66.7% [22/33; 95% CI, 48.2 to 82.0]) in patients with proven/probable PCP. Plasma cfDNA PCR offers a noninvasive testing option for early and accurate diagnosis of PCP, particularly in patients who cannot tolerate bronchoscopy.

Comparing methods for handling missing cost and quality of life data in the Early Endovenous Ablation in Venous Ulceration trial.

OBJECTIVES: This study compares methods for handling missing data to conduct cost-effectiveness analysis in the context of a clinical study. METHODS: Patients in the Early Endovenous Ablation in Venous Ulceration (EVRA) trial had between 1 year and 5.5 years (median 3 years) of follow-up under early or deferred endovenous ablation. This study compares complete-case-analysis (CCA), multiple imputation using linear regression (MILR) and using predictive mean matching (MIPMM), Bayesian parametric approach using the R package missingHE (BPA), repeated measures fixed effect (RMFE) and repeated measures mixed model (RMM). The outcomes were total mean costs and total mean quality-adjusted life years (QALYs) at different time horizons (1 year, 3 years and 5 years). RESULTS: All methods found no statistically significant difference in cost at the 5% level in all time horizons, and all methods found statistically significantly greater mean QALY at year 1. By year 3, only BPA showed a statistically significant difference in QALY between treatments. Standard errors differed substantially between the methods employed. CONCLUSION: CCA can be biased if data are MAR and is wasteful of the data. Hence the results for CCA are likely to be inaccurate. Other methods coincide in suggesting that early intervention is cost-effective at a threshold of £30,000 per QALY 1, 3 and 5 years. However, the variation in the results across the methods does generate some additional methodological uncertainty, underlining the importance of conducting sensitivity analyses using alternative approaches.

Acceptability and Feasibility of Geographically Explicit Ecological Momentary Assessment Among Men Who Have Sex with Men.

Syphilis among men who have sex with men (MSM) has increased greatly in the past twenty years in the U.S. Geographically explicit ecological momentary assessment (GEMA), in which behaviors are geotagged and contextualized in time and space, may contribute to a greater understanding of transmission risk. The objective was to determine the acceptability and feasibility of GEMA for assessing HIV and syphilis transmission risk behaviors among a sample of MSM. Participants responded to a brief survey five times a day for two weeks. Feasibility was measured by participant recruitment, enrollment, prompts received and answered, geotagged prompts, and technical interference with data collection. Acceptability was measured by ratings of enjoyment and willingness for future participation. Summaries of five behavioral measures from the brief survey were calculated. Among the 83 participants contacted, 67.5% (56) expressed interest, 98% (55) were scheduled, and 81.8% (45) were enrolled. Participants answered 78.3% (2,277) of prompts received and 87.7% (1,998) of answered prompts were geotagged. Overall, 70.5% (31) enjoyed participating and 91.1% (41) were willing to participate in the future. Among prompts answered, missingness was low for five behavioral measures (range 0.2% (4) to 0.7% (16)). Feasibility and acceptability were high and missingness was low on behavioral measures in this MSM study population. Most participants reported that they would participate again. Future work should focus on whether GEMA improves our understanding of syphilis and HIV transmission risk.

Development of the European Healthcare and Social Cost Database (EU HCSCD) for use in economic evaluation of healthcare programs.

INTRODUCTION: Costs are one of the critical factors for the transferability of the results in health technology assessment and economic evaluation. The objective is to develop a cost database at the European level to facilitate cross-border cost comparisons in different settings and explains the factors that lead to differences in healthcare costs in different countries, taking into account the differences between health systems and other factors. METHODOLOGY: The core of the database is compounded of three main categories (primary resources, composite goods and services, and complex processes and interventions) organized into 13 subcategories. A number of elements providing as detailed information of unit cost as possible were identified in order to mitigate the problem of comparability. Consortium partners validated both the database structure and selected costing items. RESULTS: Twenty-seven costing items included in the EU HCSCD resulted in 1450 unit costs when taking into account all item subtypes and countries. Cross-country differences in costs are driven by the type of resources included in the costing items (e.g., overhead costs in case of complex processes and interventions) or by the variety of existing brands and/or models and the type of unit value in most of the primary resources. CONCLUSION: The EU HCSCD is the only public unit healthcare and social cost database at European level that gather data on unit costs and explains differences in costs across countries. Its maintenance and regular data updating will enable establishing specific systems for generating and recording information that will meet many of its current limitations.

Evaluating the medical direct costs associated with prematurity during the initial hospitalization in Rwanda: a prevalence based cost of illness study.

BACKGROUND: Prematurity is still the leading cause of global neonatal mortality, Rwanda included, even though advanced medical technology has improved survival. Initial hospitalization of premature babies (PBs) is associated with high costs which have an impact on Rwanda's health budget. In Rwanda, these costs are not known, while knowing them would allow better planning, hence the purpose and motivation for this research. METHODS: This was a prospective cost of illness study using a prevalence approach conducted in 5 hospitals (University Teaching Hospital of Butare, Gisenyi, Masaka, Muhima, and Ruhengeri). It included PBs admitted from June to July 2021 followed up prospectively to determine the medical direct costs (MDC) by enumerating the cost of all inputs. Descriptive analyses and ordinary least squares regression were used to illustrate factors associated with and predictive of mean cost. The significance level was set at p < 0.05. RESULTS: A total of 123 PBs were included. Very preterm and moderate PBs were 36.6% and 23.6% respectively and the average birth weight (BW) was 1724 g (SD: 408.1 g). The overall mean MDC was $237.7 per PB (SD: $294.9) representing 28% of Gross Domestic Product (GDP) per capita per year. Costs per PB varied with weight category, prematurity degree, hospital level, and length of stay (LoS) among other variables. MDC was dominated by drugs and supplies (65%) with oxygen being an influential driver of MDC accounting for 38.4% of total MDC. Birth weight, oxygen therapy, and hospital level were significant MDC predictive factors. CONCLUSION: This study provides an in-depth understanding of MDC of initial hospitalization of PBs in Rwanda. It also indicates predictive factors, including birth weight, which can be managed through measures to prevent or delay preterm birth. IMPLICATION FOR PREMATURITY PREVENTION AND MANAGEMENT: The results suggest a need to revise the benefits and entitlements of insured people to include drugs and interventions not covered that are essential and where there are no alternatives. Having oxygen plants in hospitals may reduce oxygen-related costs. Furthermore, interventions to reduce prematurity should be evaluated using cost-effectiveness analysis since its overall burden is high.

Kratom use as more than a "self-treatment".

Background: Mitragyna speciosa (kratom) is increasingly used in the United States for its pharmacological effects. Kratom's relative novelty makes for a dynamic situation, such that use motivations are not firmly established and may be changing. Investigators and clinicians require frequent updates on kratom trends.Objectives: To assess the current state of kratom-use initiation, sourcing, motivations, preference, conceptualizations, and perceived stigma, using survey responses from current and former users.Methods: Between April-May 2021 we recontacted 289 respondents who reported lifetime kratom use (on an unrelated survey) to answer kratom-specific questions.Results: The sample (N=129) was majority female (51.9%) and white (71.9%). Most (69.0%) reported first trying kratom after 2015. Mean age of use initiation (29.9 years) was older than for other substances, including opioids. Kratom ranked as a preferred substance by 48.5%. The strongest drug association with past-year kratom use was vaped nicotine (OR=3.31,95% CI 1.23-8.88). Use was less likely among those prescribed buprenorphine in the past year (OR=0.03, CI 0.01-0.28). Past-month cannabis use (OR=4.18,CI 1.80-9.72) had the strongest association with past-month kratom use. Over 40 use motivations were endorsed, many (but not all) supporting the "self-treatment" narrative of kratom use, including use as an opioid, alcohol, or stimulant substitute. Treatment shortfalls were associated with decisions to try kratom.Conclusions: Kratom use motivations are diversifying, with multiple factors driving use. As sales continue to increase, the public-health, clinical, and policy responses to kratom should be grounded in rigorous bench-to-bedside scientific research. Comprehensive study of kratom is currently lacking.