A systematic review of interventions that impact alcohol and other drug-related harms in licensed entertainment settings and outdoor music festivals.

BACKGROUND: Harms associated with the use of alcohol and other drugs (AOD) in licensed entertainment settings (LES) and outdoor music festivals (OMF) are ongoing public health and criminal justice concerns. This systematic review provides a comprehensive, synthesized report on the evidence base of interventions that impact harm in these settings, and how they affect health, behavioral, and criminal justice outcomes. METHODS: Nine databases were searched for experimental and observational studies published between 2010 and 2021. Studies were included if they were peer-reviewed, published in English, described interventions which could impact AOD-related harms in LES or OMF (and were delivered in these environments), and reported on health, criminal justice and/or behavioral outcomes. Methodological quality was assessed using the Effective Public Health Practice Project's Quality Assessment Tool for Quantitative Studies and the Critical Appraisal Skills Program for qualitative studies. A narrative synthesis was conducted to synthesize outcomes across studies. The review protocol was registered in PROSPERO (CRD42020140004). RESULTS: Of the 48,303 studies screened, 100 met the inclusion criteria. 86 focused solely on reducing alcohol-related harm, 7 on reducing illicit drug-related harm, and 7 on both. Most (n = 88) focused on LES and evaluated changes in laws and regulations (n = 28) and/or multicomponent interventions/policies (n = 41). Multicomponent interventions showed the best results for both health (62% positive) and criminal justice (84% positive) outcomes, with 71% of studies being rated as strong quality. There was also good evidence to support the careful application of trading hour restrictions and limited but promising evidence to support medical services and drug checking. CONCLUSION: The breadth, quality and volume of evidence regarding what works in reducing AOD-related harm in recreational settings have increased in the past decade, particularly regarding LES. Findings support onsite medical services (reducing ambulance transfer rates), multicomponent interventions targeting alcohol accessibility and availability (reducing assaults), and drug checking services, but suggest other interventions such as drug detection dogs may exacerbate harm. Further, higher quality research is required to address identified gaps in the evidence base, particularly on optimal interventions within OMF, around illicit drugs more broadly and in the Global South.

Homozygous SPTA1-associated hereditary pyropoikilocytosis presenting as hydrops fetalis.

INTRODUCTION: Hereditary pyropoikilocytosis (HPP) is a heterogeneous inherited disorder of red blood cell (RBC) membrane and cytoskeletal proteins that leads to hemolytic anemia. HPP is characterized by marked poikilocytosis, microspherocytes, RBC fragmentation, and elliptocytes on peripheral blood smear. Mutations in SPTA1 can cause HPP due to a quantitative defect in α-spectrin and can lead to profound fetal anemia and nonimmune hydrops fetalis, which can be managed with intrauterine transfusion. CASE PRESENTATION: We present a case of a 26-year-old G4P2102 woman of Amish-Mennonite ancestry with a pregnancy complicated by fetal homozygosity for an SPTA1 gene variant (SPTA1c.6154delG) as well as severe fetal anemia and hydrops fetalis, which was managed with four intrauterine transfusions between 26 and 30 weeks gestation. Pre-transfusion peripheral smears from fetal blood samples showed RBC morphology consistent with HPP. The neonate had severe hyperbilirubinemia at birth, which has resolved, but remains transfusion-dependent at 6 months of life. DISCUSSION/CONCLUSION: To our knowledge, this is the first report that correlates homozygosity of the SPTA1c.6154delG gene variant with RBC dysmorphology and establishes the diagnosis of HPP.

Placental Histopathologic Findings in Fetal Hereditary Pyropoikilocytosis after Undergoing Successful Intrauterine Transfusion.

Background: The available literature on intrauterine transfusion focuses largely on its application in fetal alloimmunization rather than hereditary red cell disorders, with limited illustration of its associated histopathologic findings. Case report: We present the histologic findings in a placenta associated with preterm delivery of an infant with autosomal SPTA1 mutation following multiple intrauterine transfusions, including appropriate villous maturation, subchorionic organizing hematomas, hemosiderin-laden macrophages, and dysmorphic fetal erythrocytes within villous capillaries. Conclusion: Intrauterine transfusion is associated with placental histologic findings that reflect procedural changes without significant disruption of placental membranes or villous maturation.

Comparing police use of drug detection dogs amongst injecting and non-injecting groups of people who regularly use drugs in Australia.

INTRODUCTION: Drug detection dogs are utilised across multiple settings, however existing literature focuses predominantly on festival-based encounters. We compare drug dog encounters in non-festival settings among two samples of people who regularly use drugs, and investigate factors associated with witness only versus stop and/or search encounters. METHODS: Australians who regularly (i.e., ≥monthly) use ecstasy and/or other illegal stimulants (n = 777; Ecstasy and Related Drugs Reporting System (EDRS)) or inject illegal drugs (n = 862; Illicit Drugs Reporting System (IDRS)) were surveyed between April-June, 2019. Univariable regression analyses were used to test for differences in drug dog encounters between samples, and to identify factors associated with a more intensive drug dog encounter (namely those that involved a stop and/or search). RESULTS: People who inject drugs were less likely to witness drug dogs than those who regularly use ecstasy and/or other illegal stimulants (odds ratio (OR) 0.46; 95 % CI 0.30-0.69). They were significantly more likely than EDRS participants to report being stopped and searched (3.29; 1.68-6.44) however. Among those carrying drugs at their last stop and/or search encounter, the majority of both samples reported that their drugs were not detected by police. IDRS participants aged 35-49 were more likely to report a stop and/or search encounter than those aged 17-34; no significant associations were found among the EDRS sample. CONCLUSIONS: Despite participants who use ecstasy and/other stimulants being more likely than those who regularly inject drugs to report encountering drug dogs in non-festival settings, participants who inject drugs were more likely to report an intensive or invasive drug dog encounter and/or receiving a formal criminal justice consequence. This study reinforces questions about the efficacy and appropriateness of drug dog operations.

Co-designing drug alerts for health and community workers for an emerging early warning system in Victoria, Australia.

BACKGROUND: Alerts about changes in unregulated drug markets may be useful for supporting health and community workers to anticipate, prevent, and respond to unexpected adverse drug events. This study aimed to establish factors influencing the successful design and implementation of drug alerts for use in clinical and community service settings in Victoria, Australia. METHODS: An iterative mixed methods design was used to co-produce drug alert prototypes with practitioners and managers working across various alcohol and other drug services and emergency medicine settings. A quantitative needs-analysis survey (n = 184) informed five qualitative co-design workshops (n = 31). Alert prototypes were drafted based on findings and tested for utility and acceptability. Applicable constructs from the Consolidated Framework for Implementation Research helped to conceptualise factors that impact successful alert system design. RESULTS: Timely and reliable alerts about unexpected drug market changes were important to nearly all workers (98%) yet many reported insufficient access to this kind of information (64%). Workers considered themselves 'conduits' for information-sharing and valued alerts for increasing exposure to drug market intelligence; facilitating communication about potential threats and trends; and improving capacity for effective responding to drug-related harm. Alerts should be 'shareable' across a range of clinical and community settings and audiences. To maximise engagement and impact, alerts must command attention, be easily recognisable, be available on multiple platforms (electronic and printable formats) in varying levels of detail, and be disseminated via appropriate notification mechanisms to meet the needs of diverse stakeholder groups. Three drug alert prototypes (SMS prompt, summary flyer, and a detailed poster) were endorsed by workers as useful for supporting their work responding to unexpected drug-related harms. DISCUSSION: Alerts informed by coordinated early warning networks that offer close to real-time detection of unexpected substances can provide rapid, evidence-based drug market intelligence to inform preventive and responsive action to drug-related harm. The success of alert systems requires adequate planning and resourcing to support design, implementation, and evaluation, which includes consultation with all relevant audiences to understand how to maximise engagement with information, recommendations, and advice. Our findings about factors impacting successful alert design have utility to inform the development of local early warning systems.

Encounters with police drug detection dogs at music festivals amongst people who regularly use ecstasy and/or other illicit stimulants in Australia.

INTRODUCTION: Despite increasing evidence challenging the effectiveness and legality of police drug dog operations, these strategies remain common. We aimed to describe drug dog encounters at music festivals, behavioural adaptations taken in anticipation of their presence and consequences of encounters amongst a sample of people who regularly use MDMA/ecstasy. METHODS: Data were collected via interviewer-administered questionnaires in April-June 2019. Australians aged 16 years or older who used MDMA/ecstasy and/or other stimulants monthly in the last 6 months were recruited from capital cities via social media and word-of-mouth (n = 797). Participants reported recent drug dog encounters, encounter settings and actions taken in anticipation of and in response to encounters. RESULTS: In this sample, encounters with drug dogs at festivals were common (60%), with most participants (92%) reporting anticipating the encounter. Most (86%) of this group reported behavioural adaptations to avoid a detection, with concealing drugs well (57%) and consuming prior to entering the festival (20%) most reported. Only 4% of those who expected drug dog presence chose not to carry or consume drugs. One-quarter (26%) of those who reported an encounter were stopped by police and 4% were searched (bodily/bag search). DISCUSSION AND CONCLUSION: Most participants anticipated drug dog presence at festivals, however, were not deterred from carrying or consuming drugs. Some reported adaptations to avoid detection may increase drug-related health, social and legal harms. Our study suggests drug dog presence at festivals does not deter carriage/use of illegal drugs, and echoes concerns regarding the efficacy and appropriateness of this policing initiative.

'We don't live in a harm reduction world, we live in a prohibition world': tensions arising in the design of drug alerts.

BACKGROUND: Drug alerts designed for health and community workforces have potential to avert acute harms associated with unpredictable illicit drug markets, by preparing workers to respond to unusual drug-related events, and distribute information to service users. However, the design of such alerts is complicated by diverse needs of individuals, and broader socio-political contexts. Here, we discuss the tensions that arose in the process of co-designing drug alert templates with health and community workers. METHODS: We conducted five in-depth digital co-design workshops with 31 workers employed in alcohol and other drug and urgent care settings. Our approach to analysis was informed by Iterative Categorisation and reflexive thematic analysis methods. RESULTS: We identified five key tensions. First, there is a need to provide comprehensive information to meet the information needs of a diverse group of workers with varying knowledge levels, while also designing alerts to be clear, concise, and relevant to the work of individuals. Second, it is important that alerts do not create 'information overload'; however, it is also important that information should be available to those who want it. Third, alert design and dissemination must be perceived to be credible, to avoid 'alert scepticism'; however, credibility is challenging to develop in a broader context of criminalisation, stigmatisation, and sensationalism. Fourth, alerts must be carefully designed to achieve 'intended effects' and avoid unintended effects, while acknowledging that it is impossible to control all potential effects. Finally, while alerts may be intended for an audience of health and community workers, people who use drugs are the end-users and must be kept front of mind in the design process. CONCLUSIONS: The co-design process revealed complexities in designing drug alerts, particularly in the context of stigmatised illicit drug use, workforce diversity, and dissemination strategies. This study has highlighted the value of developing these important risk communication tools with their target audiences to ensure that they are relevant, useful, and impactful. The findings have informed the development of our drug alert prototypes and provide local context to complement existing best-practice risk-communications literature.

The Green Placental Disk: Massive Placental Disk Bilirubin Deposition Due to Maternal Hyperbilirubinemia.

BACKGROUND: Bile staining in the hepatobiliary tree is a well-known phenomenon, but bilirubin can also be deposited in and stain the umbilical cord, amniotic fluid, placental disk and placental membranes. CASE REPORT: We present a placenta with grossly greenish discoloration of the placental disk and microscopic villous bilirubin deposition due to maternal hyperbilirubinemia. Conclusion: Maternal hyperbilirubinemia causes massive bilirubin deposition in villous synctiotrophoblasts and Hofbauer cells leading to grossly green discoloration of the placental disk.

Bilateral Ovarian Sertoli-Leydig Cell Tumors Harboring DICER1 Germline and Distinct Somatic Mutations: Case Report and Literature Review.

Background: DICER1 tumor predisposition syndrome is characterized by an increased risk for development of pleuropulmonary blastoma, pituitary blastoma, multinodular thyroid goiter, thyroid carcinoma, sex cord stromal tumor, cystic nephroma, embryonal rhabdomyosarcoma, and tumors of the CNS, amongst others. Of this list, only pituitary blastoma is recognized as pathognomonic for the syndrome. Case report: We describe a 15-year-old female with bilateral, asynchronous Sertoli-Leydig cell tumors (SLCT). Both tumors harbored an identical germline frameshift mutation as well as unique somatic DICER1 hot-spot point mutations. Discussion: A review of bilateral SLCTs demonstrates that all patients with available DICER1 mutation status carried a germline DICER1 mutation (100%, 9 of 9). In cases with known somatic DICER1 status on bilateral tumors, all harbored distinct somatic mutations (100%, 5 of 5). Our findings support the notion that bilateral ovarian SLCTs are indeed separate events and do not represent recurrent or metastatic disease.

Successful Orthotopic Heart Transplantation in a Patient with Anti-U Antibody.

OBJECTIVE: The U (universal) antigen is part of the MNS blood group present at a frequency of nearly 100% in Caucasians and 98% of African Americans. The anti-U antibody is clinically significant and has been reported to cause hemolytic transfusion reactions and hemolytic disease of the fetus and newborn. METHODS: Routine forward and backward typing, direct antiglobulin testing, and an antibody screen were performed. In addition, red blood cell phenotype and adsorption studies were also performed. RESULTS: The patient was found to have a rare anti-U antibody, rendering all available inventory in our hospital incompatible for transfusion. CONCLUSION: This is the first reported case of solid organ transplantation in a patient with an anti-U alloantibody. Appropriate pretransplant evaluation and coordination between the clinical team and transfusion medicine service must be optimized to procure rare packed red blood cell units in a timely manner.

Artificial Intelligence in Plasma Cell Myeloma: Neural Networks and Support Vector Machines in the Classification of Plasma Cell Myeloma Data at Diagnosis.

BACKGROUND: Plasma cell neoplasm and/or plasma cell myeloma (PCM) is a mature B-cell lymphoproliferative neoplasm of plasma cells that secrete a single homogeneous immunoglobulin called paraprotein or M-protein. Plasma cells accumulate in the bone marrow (BM) leading to bone destruction and BM failure. Diagnosis of PCM is based on clinical, radiologic, and pathological characteristics. The percent of plasma cells by manual differential (bone marrow morphology), the white blood cell (WBC) count, cytogenetics, fluorescence in situ hybridization (FISH), microarray, and next-generation sequencing of BM are used in the risk stratification of newly diagnosed PCM patients. The genetics of PCM is highly complex and heterogeneous with several genetic subtypes that have different clinical outcomes. National Comprehensive Cancer Network guidelines recommend targeted FISH analysis of plasma cells with specific DNA probes to detect genetic abnormalities for the staging of PCM (4.2021). Recognition of risk categories through training software for classification of high-risk PCM and a novel way of addressing the current approaches through bioinformatics will be a significant step toward automation of PCM analysis. METHODS: A new artificial neural network (ANN) classification model was developed and tested in Python programming language with a first data set of 301 cases and a second data set of 176 cases for a total of 477 cases of PCM at diagnosis. Classification model was also developed with support vector machines (SVM) algorithm in R studio and interactive data visuals using Tableau. RESULTS: The resulting ANN algorithm had 94% accuracy for the first and second data sets with a classification summary of precision (PPV): 0.97, recall (sensitivity): 0.76, f1 score: 0.83, and accuracy of logistic regression of 1.0. SVM of plasma cells versus TP53 revealed a 95% accuracy level. CONCLUSION: A novel classification model based only on specific morphological and genetic variables was developed using a machine learning algorithm, the ANN. ANN identified an association of WBC and BM plasma cell percentage with two of the high-risk genetic categories in the diagnostic cases of PCM. With further training and testing of additional data sets that include morphologic and additional genetic rearrangements, the newly developed ANN model has the potential to develop an accurate classification of high-risk categories of PCM.

Profile and correlates of colorimetric reagent kit use among people who use ecstasy/MDMA and other illegal stimulants in Australia.

BACKGROUND: Colorimetric reagent kits can provide information about the compounds present in drug samples. This study aimed to identify patterns and correlates of colorimetric reagent kit use, as well as behavioural outcomes of testing, amongst people who use illegal stimulants in a context that lacks permanent government-sanctioned drug checking services. METHODS: Australians residing in capital cities who reported regularly using ecstasy/MDMA and/or other illegal stimulants ≥monthly in the past six months were recruited via social media and word-of-mouth from April-July 2019 (N = 792). Participants were asked about testing the contents and/or purity of illegal drugs, and features of last colorimetric reagent kit use. Logistic regression identified correlates of last using a kit (referent: no use of drug checking technology to test drug contents/purity in the past year). RESULTS: Over one-third (36%) reported testing drug contents and/or purity; of this group, 86% had last used a colorimetric reagent kit. On the last occasion, 52% reported someone else had conducted testing; 58% said testing occurred <24 h before planned drug use; and 24% reported testing for quantity of a substance. Correlates of drug checking comprised: being younger, male, past six-month use of new psychoactive substances, accessing community-based health services for alcohol or other drug reasons, selling drugs for cash profit, obtaining information from peers who had tried the drug, and searching online for reports of the drug by stamp/appearance. The majority (84%) tested a substance they had been sold and/or given as MDMA; of these, 87% detected MDMA. Of those who expected and detected MDMA, 29% and 11% reported results to their peers and dealer, respectively. CONCLUSION: People who use ecstasy/MDMA and/or other illegal stimulants seek out objective information about substance contents. In countries that lack permanent government-sanctioned drug checking services, it is important to acknowledge that people already engage in drug checking but with suboptimal technologies and without tailored specialist advice and education.

Second Report of PDE10A-BRAF Fusion in Pediatric Spindle Cell Sarcoma With Infantile Fibrosarcoma-Like Morphology Suggesting PDE10A-BRAF Fusion Is a Recurrent Event.

Infantile/congenital fibrosarcoma (IFS) is the most common soft tissue tumor in children less than one year of age. The most common anatomic site of IFS is in the extremities or trunk, and rarely in the abdomen or retroperitoneum. Approximately 70-90% of cases are characterized by a distinct t(12;15)(p13;q25) translocation resulting in an ETV6-NTRK3 gene fusion. As such, TRK inhibitors are considered frontline therapy in TRK-fusion positive IFS. The ETV6-NTRK3 fusion is also detected in congenital mesoblastic nephroma (CMN) and less frequently in myeloid leukemias, secretory breast carcinoma, and mammary-type secretory carcinoma of the skin and salivary glands. Infrequently, cases of tumors with IFS-like morphology without the characteristic ETV6-NTRK3 gene fusion have been identified. Herein, an ETV6-NTRK3 fusion negative spindle cell sarcoma with IFS-like morphology subjected to genomic profiling revealed a PDE10A-BRAF fusion, a fusion event that has been detected previously in an isolated case of undifferentiated infantile sarcoma.

Low rates of anti-recipient isohemagglutinins in ABO incompatible hematopoietic stem cell transplants.

INTRODUCTION: Isohemagglutinins occur naturally and form in an 'opposite' (antigen-negative) pattern to a patient's ABO blood type. Patients undergoing minor and bidirectional ABO incompatible hematopoietic stem cell transplantation (HSCT) may demonstrate detectable antibodies against their native blood type. In this study, we sought to characterize the rates of such antibody formation and evaluate the clinical significance of our findings. MATERIALS AND METHODS: An internal database of HSCT patients at an academic medical center was queried for ABO incompatible transplant patients from 2009-2019. Serum typing results, clinical histories, and laboratory data were compiled and reviewed. RESULTS: A total of 182 minor and bidirectional ABO incompatible HSCT patients were identified. Anti-recipient isohemagglutinins were found in 9% (16/182) of the HSCT patients. The rate was higher in patients with minor incompatibility (12%: 15/127) versus bidirectional ABO incompatibility (2%: 1/55) (p = 0.04). No anti-recipient isohemagglutinins were identified in umbilical cord HSCT patients (0%: 0/7). Serologic agglutination reactions of recipient isohemagglutinins were overall mostly weak (13/16 weak + to 1+). There was a trend towards a higher rate of acute graft-versus-host-disease in patients with anti-recipient isohemagglutinins compared to those without (75% vs. 53%; p = 0.12), though not statistically significant. Rates of alloimmunization to minor red cell antigens were similar between the two groups. Few patients showed laboratory evidence of hemolysis at 12 months follow up. DISCUSSION AND CONCLUSIONS: Anti-recipient isohemagglutinins occur at low rates in ABO incompatible HSCT and are significantly more common in minor ABO incompatible transplant compared to bidirectional transplants. Larger cohort studies are needed to better understand the relationship between anti-recipient isohemagglutinins and HSCT outcomes.

Structural and functional changes in an Australian high-level drug trafficking network after exposure to supply changes.

BACKGROUND: Illicit drug markets and associated supply changes (including changes in availability and purity) have been studied for many years but with limited attention to how drug trafficking networks adapt to such changes and the consequences thereof: the aim of this study. METHODS: A longitudinal social network analysis was applied to a high-level drug trafficking network which supplied methamphetamine and other drugs over 15 years in Melbourne, Australia (1993-2007). Data were extracted from judges' sentencing comments, a biography, and mainstream media. Five time periods were devised, and supply changes (distinguishing between law-enforcement-caused and non-law-enforcement-caused) were coded in each period. Then, the associated structural and functional changes in the network were analysed within and between periods. RESULTS: Thirty-two supply changes were identified, of which 59% were law-enforcement-caused and 41% not. Temporally associated structural and functional changes included a shift from mostly international trafficking to mostly domestic manufacture (and vice versa), recruiting corrupted public officials, decentralisation, as well as changes in network density, roles, and size. Despite 32 supply changes, the network continued to sell large quantities of drugs for at least 15 years. CONCLUSION: This research highlighted the complex adaptive nature of the illicit drug trade and its resilience to market change. Supply changes were associated with a variety of structural and functional changes in the network, some of which resulted in negative consequences such as corruption or the increased domestic manufacture of methamphetamine.

The price and mark up of pharmaceutical drugs supplied on the black market.

BACKGROUND: Research examining illicit drug markets has shown that price affects consumption and mark ups are extremely high. However, the economics of black market pharmaceutical supply remains unknown, despite increasing harms due to pharmaceuticals. METHODS: Semi-structured, telephone interviews were conducted in Australia with 51 people involved in supplying pharmaceuticals in the previous six months. Interviews were audio-recorded, transcribed and quantitative information on costs, sale price, quantity and frequency of supply were coded and used to calculate the mark up ratio for each drug transaction 'cycle', accounting for distribution via selling, gifting and trading. Mixed effects gamma regressions were used to identify predictors of price and mark up, clustering by participant. RESULTS: There were 29 drugs supplied over 111 cycles, including hypnotic-sedatives (38%), pharmaceutical opioids (32%), stimulants (18%) and others (12%). Sedatives were sold at lower prices than opioids and there was a negative relationship between unit price and transaction size, consistent with a discount effect. For every dollar spent acquiring the drugs, the supplier earned a median of $3.19. Cycles involving the distribution of drugs sourced via intermediaries (e.g. friends/family) had lower mark up than drugs sourced directly from the medical system. CONCLUSION: To our knowledge, this is one of few studies to analyse economic aspects of the pharmaceutical black market from a supply perspective. There were a small number of cycles that realised large profits that may warrant different types of policy responses, however for most suppliers in our sample gross revenue and gross profit was modest.

Development and Validation of a Feline Medial Saphenous Venipuncture Model and Rubric.

Cats are extremely popular pets with the reputation of being uncooperative for even common procedures, such as venipuncture. In this study, we sought to create and validate a cat medial saphenous venipuncture model and rubric for use in veterinary training. The validation framework consisted of content evidence, internal structure evidence, and relationship with other variables. Eleven veterinarians and veterinary technicians who were experienced with the procedure evaluated the model by means of a survey. These experienced participants, along with 25 veterinary students who were novices at the skill, performed venipuncture on the model while being digitally recorded. One hundred percent of the experienced participants and 88% of the novices reported that the model was helpful for teaching feline medial saphenous venipuncture. They identified a few areas for continued improvement, including increasing the blood flow rate and decreasing the vessel wall rigidity. Experienced users' rubric scores were significantly higher than novice students' (experienced, M = 13.4; novice M = 16.5; p = .05), suggesting that the model's features were adequate to differentiate the performances of various users. Internal consistency of the eight-item rubric was acceptable at .74. These results supported validation of the cat medial saphenous model and rubric for use in veterinary education.