Three noteworthy idiosyncrasies related to Canada's opioid-death crisis, and implications for public health-oriented interventions.

Canada has been experiencing a prolonged public health-crisis of high rates of overdose deaths caused by exceptionally potent/toxic, illicit opioid use. While many key features of this drug death epidemic are well-documented, several idiosyncratic aspects with relevance for public health-oriented interventions are not adequately recognised. These include: (i) the discrepant opioid patterns pan-Canada, with large majorities of opioid deaths caused by illicit fentanyl drugs in Western, but not Eastern regions where prescription-type opioid prevail; (ii) the environments of overdose deaths, where vast majorities occur in 'residential' or other shelter-type settings, presenting barriers for emergency interventions rather than health protection; and (iii) shifting drug use modes, where now majorities of overdose deaths are associated with drug 'inhalation' (instead of 'injection') in contexts of potent/toxic drug supply. We briefly describe these factors and related implications for intervention programming towards an improved response to the drug death-crisis.

"Safer Drug Supply" Measures in Canada to Reduce the Drug Overdose Fatality Toll: Clarifying Concepts, Practices and Evidence Within a Public Health Intervention Framework.

North America has been home to an unprecedented crisis of drug overdose deaths, driven largely by drug users' exposure to highly potent and toxic, illicit opioid drugs (e.g., fentanyl). Although a large and diverse menu of interventions (e.g., targeted prevention or treatment measures) has been implemented or expanded in Canada, these have not effectively managed to revert and reduce this excessive death toll. Given the fact that these interventions do not directly aim to address toxic drug exposure as the primary vector and cause of acute overdose deaths, public health-oriented "safer drug supply" measures have been initiated in local settings across Canada. These safer supply initiatives provide users with prescribed, pharmaceutical-grade drug supply with the aim of reducing overdose and death risks. These measures have been criticized but also misconstrued from several angles, e.g., as representing inadequate medical or even unethical and harmful practice. Related concerns regarding "diversion" have been raised. In this Perspective, we briefly address some of these issues and clarify selected issues of elementary concepts, practices, and evidence related to safer supply measures within a public health-oriented intervention framework. These measures are also discussed in reference to other, comparable types of public health-oriented emergency health or survival care standards, while considering the extreme contexts of an ongoing, acute drug death crisis in Canada.

Risk-thresholds for the association between frequency of cannabis use and the development of psychosis: a systematic review and meta-analysis.

BACKGROUND: Epidemiological studies show a dose-response association between cannabis use and the risk of psychosis. This review aimed to determine whether there are identifiable risk-thresholds between the frequency of cannabis use and psychosis development. METHODS: Systematic search of Embase, MEDLINE, PsycINFO, CINAHL, and Web of Science for relevant studies (1 January 2010-26 April 2021). Case-control or cohort studies that investigated the relationship between cannabis use and the risk of psychosis development that reported effect estimates [odds ratios (OR), hazard ratios (HR), risk ratios (RR)] or the raw data to calculate them, with information on the frequency of cannabis consumption were included. Effect estimates were extracted from individual studies and converted to RR. Two-stage dose-response multivariable meta-analytic models were utilized and sensitivity analyses conducted. The Newcastle Ottawa Scale was used to assess the risk of bias of included studies. RESULTS: Ten original (three cohorts, seven case-control) studies were included, including 7390 participants with an age range of 12-65 years. Random-effect model meta-analyses showed a significant log-linear dose-response association between cannabis use frequency and psychosis development. A restricted cubic-splines model provided the best fit for the data, with the risk of psychosis significantly increasing for weekly or more frequent cannabis use [RR = 1.01, 95% confidence interval (CI) 0.93-1.11 yearly; RR = 1.10, 95% CI 0.97-1.25 monthly; RR = 1.35, 95% CI 1.19-1.52 weekly; RR = 1.76, 95% CI 1.47-2.12 daily]. CONCLUSION: Individuals using cannabis frequently are at increased risk of psychosis, with no significant risk associated with less frequent use. Public health prevention messages should convey these risk-thresholds, which should be refined through further work.

Identifying risk-thresholds for the association between frequency of cannabis use and development of cannabis use disorder: A systematic review and meta-analysis.

BACKGROUND: Cannabis use disorder (CUD) affects one-in-five cannabis users, presenting a major contributor to cannabis-associated disease burden. Epidemiological data identify the frequency of cannabis use as a risk factor for CUD. This review aimed to determine quantifiable risk-thresholds of the frequency of cannabis use for developing CUD. METHODS: Systematic search of Medline, EMBASE, PsycInfo, CINAHL, and Web of Science for cohort/case-control studies that assessed the association between frequency of cannabis use and CUD from 2000 to 2022. Effect estimates were converted to risk ratios (RR). A random-effects multi-level multivariate meta-analytic approach was utilized, and sensitivity analyses conducted. Quality of included studies was assessed with the Newcastle Ottawa Scale. RESULTS: Six prospective cohort studies were included in this review, drawn from two main source studies. Random-effect modeling showed a significant log-linear dose-response association between the frequency of cannabis use and CUD risk (p < 0.0001). The risk of CUD increased from RR:2.03 (95% CI:1.85-2.22) for 'yearly' use, to RR:4.12 (95% CI:3.44-4.95) for 'monthly" use, RR:8.37 (95% CI:6.37-11.00) for 'weekly' use, and RR:16.99 (95% CI:11.80-24.46) for 'daily' use. Multi-level modeling showed an absolute risk increase (ARI) from 3.5% (95% CI:2.6-4.7) for 'yearly' use, to 8.0% (95% CI:5.3-12.1) for 'monthly' use, to 16.8% (95% CI:8.8-32.0) for 'weekly' use, and 36% (95% CI:27.047.9) for 'daily' use. CONCLUSION: A limited risk of CUD as a potential outcome of cannabis use exists even at infrequent levels of use, but significantly increases as frequency of use increases. Corresponding information should be conveyed to cannabis users as part of targeted prevention messaging to promote safer cannabis use.

Use of breast milk in infants with uncomplicated gastroschisis: A retrospective cohort study.

BACKGROUND: Infants with gastroschisis often experience slow return of bowel function following closure. The purpose of this study was to determine whether exclusive breast milk is associated with decreased time to enteral autonomy. METHODS: We conducted a retrospective cohort study of infants with uncomplicated gastroschisis from a tertiary pediatric hospital. The primary outcome was enteral autonomy, defined as days from initiating enteral feeds to stopping parenteral nutrition. Secondary outcomes included days of parenteral nutrition, length of stay, positive culture, necrotizing enterocolitis, cholestasis, additional surgery, readmission, and mortality. RESULTS: We identified 100 infants with gastroschisis treated from 2005 to 2019. Twenty-five were excluded due to gestational age <32 weeks, birth weight <1500 g, or gastroschisis-associated complications (e.g., intestinal atresia). Seventy-five were included in the analysis. Mean gestational age was 36 weeks, 48% were female, and all were diagnosed antenatally. Sixty-five infants (87%) received exclusive maternal (n = 64) or donor (n = 1) breast milk, while 10 others (13%) were fed formula for 1-16 days (mean 7 days). Two infants received formula only. Demographics and gastroschisis prognostic scores were similar between groups. Infants who were given breast milk exclusively demonstrated decreased time to enteral autonomy (median 18 versus 25 days, p = 0.023) and shorter duration of parenteral nutrition (median 20 versus 26 days, p = 0.037). CONCLUSION: Exclusive breast milk may be associated with improved outcomes among infants with gastroschisis. Further research is needed to evaluate the economic impact of this association and explore possible confounders. These efforts may expand the role of donor breast milk for these patients.

Postoperative management of pediatric patients undergoing minimally invasive repair of pectus excavatum: Where are we now?

PURPOSE: Minimally invasive repair of pectus excavatum (MIRPE) often leads to a painful and challenging recovery period. This study aims to describe the postoperative management of pediatric patients undergoing MIRPE and compare postoperative outcomes between patients using different routes of postoperative analgesia. METHODS: Retrospective chart review of pediatric patients who underwent MIRPE from July 2003 to September 2019 at a single pediatric tertiary care center. Data on pain management and course of hospital stay were ascertained. Descriptive statistics, Mann-Whitney U and Pearson Chi-Square tests were used to analyze data. A p-value <0.05 was considered significant. RESULTS: Of the 115 patients identified, 58 (50.4%) managed pain postoperatively using thoracic epidural and 57 (49.6%) used intravenous patient-controlled analgesia (IVPCA). The transition from the predominant use of epidural to IVPCA for MIRPE occurred between 2012 and 2013. Higher pain scores were reported by the IVPCA group at 6 h (p<0.001) and 12 h (p<0.001) postoperative. Patients using IVPCA had lower postoperative opioid consumption (p<0.001) and switched to oral opioids sooner than the epidural group (p<0.001). Fewer patients in the IVPCA group required urinary catheterization (p<0.001). Patients using IVPCA had a shorter hospital stay (4 days [IQR 4-5]) compared to the epidural group (5.5 [IQR 5-6]; p<0.001). Readmission was comparable at 3.48% in the total sample. CONCLUSION: Patients using intravenous patient-controlled analgesia reported higher pain scores however, this route of analgesia was associated with shorter hospital stay. Prospective studies designed to address moderator variables are required to confirm findings and develop standardized recovery protocols.

Elevated international normalized ratio is correlated with large volume transfusion in pediatric trauma patients.

BACKGROUND: Pediatric trauma patients may benefit from a balanced transfusion strategy, however, determining when to activate massive transfusion protocols remains uncertain. The purpose of this study was to explore whether certain scoring systems can predict the need for large volume transfusion. METHODS: We conducted a retrospective review of pediatric trauma patients who presented to our center and required a transfusion of packed red blood cells. Baseline laboratory and clinical data were used to calculate Trauma Associated Severe Hemorrhage (TASH) score and a previously reported composite of acidosis and coagulopathy. RESULTS: We identified 518 pediatric trauma patients who presented to our center between January 1, 2013 and December 31, 2018. These patients were less than 18 years of age (mean 9.6 years) and had an injury severity score ranging from 1 to 50 (mean 11.3). Forty-three patients (8.3%) received a transfusion within 24 hours of presentation, ranging from 4 to 139 mL/kg of packed red blood cells (mean 23.1 mL/kg). Transfusion volume was associated with acidosis and coagulopathy scores (r = 0.37, p = 0.033) and international normalized ratio (INR) (r = 0.34, p = 0.03) but not TASH (p = 0.72). Patients with INR≥1.3 received a higher mean volume of packed red cells compared to those with normal values (34 versus 18 mL/kg, p = 0.046). CONCLUSION: Pediatric trauma patients who undergo transfusion of packed red blood cells are likely to require large volume transfusion if their baseline INR is ≥1.3. These patients may benefit from a balanced transfusion strategy, such as utilization of massive transfusion protocols or whole blood.

Lower-Risk Cannabis Use Guidelines (LRCUG) for reducing health harms from non-medical cannabis use: A comprehensive evidence and recommendations update.

BACKGROUND: Cannabis use is common, especially among young people, and is associated with risks for various health harms. Some jurisdictions have recently moved to legalization/regulation pursuing public health goals. Evidence-based 'Lower Risk Cannabis Use Guidelines' (LRCUG) and recommendations were previously developed to reduce modifiable risk factors of cannabis-related adverse health outcomes; related evidence has evolved substantially since. We aimed to review new scientific evidence and to develop comprehensively up-to-date LRCUG, including their recommendations, on this evidence basis. METHODS: Targeted searches for literature (since 2016) on main risk factors for cannabis-related adverse health outcomes modifiable by the user-individual were conducted. Topical areas were informed by previous LRCUG content and expanded upon current evidence. Searches preferentially focused on systematic reviews, supplemented by key individual studies. The review results were evidence-graded, topically organized and narratively summarized; recommendations were developed through an iterative scientific expert consensus development process. RESULTS: A substantial body of modifiable risk factors for cannabis use-related health harms were identified with varying evidence quality. Twelve substantive recommendation clusters and three precautionary statements were developed. In general, current evidence suggests that individuals can substantially reduce their risk for adverse health outcomes if they delay the onset of cannabis use until after adolescence, avoid the use of high-potency (THC) cannabis products and high-frequency/-intensity of use, and refrain from smoking-routes for administration. While young people are particularly vulnerable to cannabis-related harms, other sub-groups (e.g., pregnant women, drivers, older adults, those with co-morbidities) are advised to exercise particular caution with use-related risks. Legal/regulated cannabis products should be used where possible. CONCLUSIONS: Cannabis use can result in adverse health outcomes, mostly among sub-groups with higher-risk use. Reducing the risk factors identified can help to reduce health harms from use. The LRCUG offer one targeted intervention component within a comprehensive public health approach for cannabis use. They require effective audience-tailoring and dissemination, regular updating as new evidence become available, and should be evaluated for their impact.

An overview of select cannabis use and supply indicators pre- and post-legalization in Canada.

BACKGROUND: Canada implemented the legalization and regulation of non-medical cannabis use, production and sale in 2018 aiming to improve public health and safety. While outcomes from legalization reforms in other jurisdictions mostly rely on US-based data have been assessed to be mixed, Canadian data are only emerging. We compiled select population-level data on key indicators to gauge initial developments from pre- to post-legalization of cannabis in Canada. METHODS: We examined indicators data focusing on the following topics: prevalence of cannabis use, frequency of use, methods/products of consumption, driving after cannabis use, and cannabis sourcing. Indicator data were obtained mostly from national and some provincial population surveys. Prevalence or percentages for the indicators pre- and post-legalization (e.g., 2017- 2020), including confidence intervals were reported, with changes noted, as available in and indicated by the data sources. RESULTS: Data suggested selected increases in cannabis use prevalence, mostly among mid- and older- but possibly also younger (e.g., under legal use age) users. Frequency of use and driving after cannabis use among active users do not appear to have changed. Methods of cannabis use show diversifying trends, with decreases in smoking and increases in alternatives use modes (e.g., edibles, vaping). There is a clearly increasing trend towards accessing cannabis from legal sources among adults, while under-legal-use-age youth do not appear to experience heightened barriers to obtaining cannabis in legalization contexts. CONCLUSIONS: Preliminary indicators on cannabis legalization in Canada show a mixed picture, some similar to US-based developments. While some use increases are observed, these do not necessarily represent indications of increases in cannabis-related harm, also since key (e.g., hospitalization or injury) data are lacking to date. There is a gradual embracing of legal supply sources of cannabis among users, which can be expected to serve public health and safety objectives. At the same time, cannabis use and access among under-age users as a principally vulnerable group do not appear to be hindered or reduced by legalization.

Improved documentation following the implementation of a trauma registry: A means of sustainability for trauma registries in low- and middle-income countries.

INTRODUCTION: Trauma registries in low- and middle-income countries (LMICs) are critical for improving trauma care; however, while some registries have been established in low-income settings, few are sustained due to a lack of sustainable funding. In many LMIC institutions, funding is dependent on documentation of trauma patients, but patient records may be of poor quality, missing, or incomplete. The development of a trauma registry and electronic patient registration system could be used to improve documentation of trauma patients in a low-income setting and lead to increased funding for trauma care. METHODS: A retrospective chart review of trauma patients at Mbarara Regional Referral Hospital in Uganda was performed, documenting the monthly admissions from January 2015-July 2016 prior to the establishment of a trauma registry. A trauma registry and electronic patient registration system were established in 2017, and monthly admissions from February 2017-December 2019 were documented. A negative binomial regression analysis was performed comparing the incident rate of admission pre-implementation of the registry compared to post-implementation, adjusting for month and year. Completeness of trauma patient records was also assessed. RESULTS: Prior to the implementation of the trauma registry and patient registration system (2015-2016), there was a mean of 5.2 (SD 4.4) trauma records per month identified. Following the implementation of the trauma registry, a mean of 103.4 trauma records per month were documented (SD 32.0) for an increased incident rate ratio of 20.9 (95% CI 15.7-27.6, p<0.001). There was also a significant increase in percentage of documents completed (OR 49.1, CI 12.4-193.7, p<0.001). DISCUSSION: Following the implementation of a trauma registry and electronic patient registration system at this low-income country hospital, an increase of 20.9 times completed trauma patient documentation was identified, and completion of the records improved. This more accurate documentation could be used to apply for increased government funding for trauma patients and sustain the trauma registry in the long term and could represent a means of long-term sustainability for other trauma registries in LMICs.

Cost effectiveness of the quality assurance and performance improvement project for suspected appendicitis study.

INTRODUCTION: Appendicitis is the most common pediatric emergent surgical condition, with 77,000 American pediatric admissions costing $680 million US annually. Diagnosing appendicitis can be challenging. The prospective Quality Assurance and performance improvement project for suspected aPPEndicitis (QAPPE) study implemented a standardized appendicitis assessment pathway. This current study aims to assess the cost-effectiveness of the QAPPE pathway. METHODS: QAPPE data (February 2018-January 2019) were compared to retrospective data from the year prior (January-December 2017). Patients aged <18, presenting with suspicion of appendicitis were identified using the emergency department patient database. Patients were excluded if they were transferred from an outside center or if appendicitis was not suspected. Study arms were compared using Student's t-test and assessed with standard costing techniques. The Incremental Cost-Effectiveness Ratio (ICER) was determined. Deterministic and probabilistic sensitivity analyses of the model were performed. Effectiveness was assessed by percent of negative appendectomies where alternate diagnosis was made intraoperatively or histologically. Significance was set at p < 0.05. RESULTS: QAPPE (n = 247) and traditional care (n = 234) patients were compared. Traditional care had higher admission frequency and lower pediatric appendicitis score. Demographics between all included patients and those admitted were similar overall. Patient costs were $3656.32 (95% CI $2407-$5250) Canadian (CAD) for QAPPE and $3823.56 (95% CI $2604-$5451) CAD for traditional care. QAPPE was the dominant strategy in the base model and probabilistic simulation found it favored in 64.7% of model iterations with a willingness to pay of $70,000 CAD. CONCLUSION: Using the QAPPE pathway to assess patients with suspected appendicitis reduced costs and improved effectiveness of patient care. LEVEL OF EVIDENCE: 2.

Quality Assurance and Performance Improvement Project for Suspected Appendicitis.

INTRODUCTION: Considerable variability exists in the diagnosis and management of acute appendicitis, affecting both quality and costs of care. This prospective cohort study aimed to decrease unnecessary radiological investigations, standardize radiological imaging, avoid unnecessary hospital admissions, and decrease our institution rate of negative appendectomy. METHODS: A multidisciplinary appendicitis care pathway was implemented. This pathway involved the use of the Pediatric Appendicitis Score, standardization of ultrasound reporting, and risk stratification to determine patient disposition. Patients were prospectively enrolled in the pathway and compared a preimplementation retrospective cohort. RESULTS: We included 235 patients in this study that took place between February 2017 and January 2018. An 88.5% pathway adherence rate for appropriate referral for ultrasounds, an 84% compliance rate for correct risk stratification, and the need for a surgical consult were achieved. After implementation, standardization of ultrasound (U/S) reporting increased from 0% to 78%. The rate of computed tomography utilization decreased from 7.3% to 4.7%. An appendectomy was completed in 68 (29%) of patients. There was only 1 (1.5%) negative appendectomy, compared to the prepathway institutional negative appendectomy rate of 4%. CONCLUSION: The implementation of a standardized, evidence-based, appendicitis care pathway has the potential to improve quality of care by reducing negative appendectomies, unnecessary computed tomography scans, and unnecessary hospital admissions. The participation of the emergency and diagnostic imaging departments is critical to the successful implementation of this quality improvement measure. This simple, effective model can be easily implemented at other centers to improve the care of children.

Ethical considerations in global surgery: a scoping review.

Introduction: An unmet burden of surgical disease exists worldwide and is disproportionately shouldered by low-income and middle-income countries (LMICs). As the field of global surgery grows to meet this need, ethical considerations need to be addressed. Currently, there are no formal guidelines to help inform relevant stakeholders of the ethical challenges and considerations facing global surgical collaborations. The aim of this scoping review is to synthesise the existing literature on ethics in global surgery and identify gaps in the current knowledge. Methods: A scoping review of relevant databases to identify the literature pertaining to ethics in global surgery was performed. Eligible articles addressed at least one ethical consideration in global surgery. A grounded theory approach to content analysis was used to identify themes in the included literature and guide the identification of gaps in existing literature. Results: Four major ethical domains were identified in the literature: clinical care and delivery; education and exchange of trainees; research, monitoring and evaluation; and engagement in collaborations and partnerships. The majority of published literature related to issues of clinical care and delivery of the individual patient. Most of the published literature was published exclusively by authors in high-income countries (HICs) (80%), and the majority of articles were in the form of editorials or commentaries (69.1%). Only 12.7% of articles published were original research studies. Conclusion: The literature on ethics in global surgery remains sparse, with most publications coming from HICs, and focusing on clinical care and short-term surgical missions. Given that LMICs are frequently the recipients of global surgical initiatives, the relative absence of literature from their perspective needs to be addressed. Furthermore, there is a need for more literature focusing on the ethics surrounding sustainable collaborations and partnerships.

The fragility of statistically significant findings from randomized controlled trials in pediatric appendicitis: A systematic review.

PURPOSE: Randomized controlled trials (RCT) in pediatric appendicitis remain limited, and the robustness of available evidence is unknown. The aim of this study was to determine the fragility of results in pediatric appendicitis RCTs. METHODS: A systematic search of Embase and MEDLINE was performed. Eligible studies were two-armed RCTs that included at least one statistically significant dichotomous outcome, had parallel-group allocation, and assessed pediatric patients (0-17) with a primary diagnosis of appendicitis. The Fragility Index (FI) for one statistically significant outcome per trial was calculated using a Fisher's exact test, with statistical significance set at p < 0.05. RESULTS: Six studies were identified for inclusion. Studies included a median of 103 patients (interquartile range [IQR] 86-127), with a median of 18 (IQR 4.5-41.25) events for analyzed outcomes. The primary outcome variable was included in analysis for 4(67%) studies. The median FI across studies was 3 (IQR 0.75-4.25), with results ranging from 0 to 5. Results indicate that overall, converting 3 patients from non-events to events in a single trial arm would change the significant dichotomous outcome to nonsignificant. CONCLUSION: The fragility of results in RCTs in pediatric appendicitis should be considered before clinical practice is changed. Investigators should consider reporting the FI alongside study results, as p-values alone may be misleading. TYPE OF STUDY: Randomized Controlled Trial. LEVEL OF EVIDENCE: Level I.