Take-home drug checking as a novel harm reduction strategy in British Columbia, Canada.

BACKGROUND: Drug checking is a harm reduction strategy used to identify components of illicitly obtained drugs, including adulterants, to prevent overdose. This study evaluated the distribution of take-home fentanyl test strips to people who use drugs (PWUD) in British Columbia, Canada. The primary aim was to assess if the detection of fentanyl in opioid samples was concordant between a take-home model and testing by trained drug checking staff. METHODS: Take-home fentanyl test strips were distributed at ten sites providing drug checking services from April to July 2019. The fentanyl positivity of the aggregate take-home and on-site drug checking groups were compared by class of substance tested. An administered survey assessed acceptability and behaviour change. RESULTS: 1680 take-home results were obtained from 218 unique participants; 68% of samples (n=1142) were identified as opioids and 23% (n=382) were stimulant samples. During this period, 852 samples were tested using on-site drug checking. The fentanyl positivity of opioid samples was 90.0% for take-home samples and 89.1% for on-site samples (Difference 0.8% (95% CI -2.3% to 3.9%)). These results were not affected by previous experience with test strips. Fentanyl positivity of stimulants in the take-home group was higher than on-site (24.7% vs. 3.2%), but the study was underpowered to conduct statistical analysis on this sub-group. When fentanyl was detected, 27% of individuals reported behaviour change that was considered safer/positive. Greater than 95% of participants stated they would use fentanyl test strips again. CONCLUSIONS: Take-home fentanyl test strips used by PWUD on opioid samples can provide similar results to formal drug checking services and are a viable addition to existing overdose prevention strategies. Use of this strategy for detection of fentanyl in stimulant samples requires further evaluation. This intervention was well accepted and in some participants was associated with positive behaviour change.

Patient preferences for first-line treatment of classical Hodgkin lymphoma: a US survey and discrete choice experiment.

A cross-sectional online survey, including a discrete choice experiment (DCE), was used to investigate first-line treatment preferences in patients with classical Hodgkin lymphoma (cHL) in the United States; 141 patients (median age 35.0 years) participated. In the DCE, risk of progression at 2 years (progression free survival) had the highest relative importance to patients (31.3%) when considering first-line treatments, followed by 2-year overall survival (OS; 26.9%), on-treatment pulmonary toxicity (23.3%), and on-treatment peripheral neuropathy (18.5%). Marginal rate of substitution analyses demonstrated that a 0.44% and 0.09% increase in 2-year OS was required for patients to accept a 1% increase in the risk of disease progression at 2 years and peripheral neuropathy, respectively. A 2.6% increase in 2-year OS was needed to accept a 7% rather than a 2% risk of pulmonary toxicity. In summary, patients with cHL rated survival attributes as more important than drug-related toxicity when considering first-line treatments.

Efficacy and safety of first-line carboplatin-versus cisplatin-based chemotherapy for non-small cell lung cancer: A meta-analysis.

OBJECTIVES: Platinum-based chemotherapy is the mainstay of first-line (1L) therapy for advanced non-small cell cancer (NSCLC). The objective of this study was to evaluate the relative efficacy, safety, and health-related quality of life (HRQoL) of carboplatin- versus cisplatin-based chemotherapy in 1L NSCLC. MATERIALS AND METHODS: A meta-analysis by the Cochrane group (2013) was updated. Systematic searches of CENTRAL, Medline, Embase, Latin American and Caribbean Health Sciences database, clinicaltrials.gov and conference proceedings were conducted to include randomized controlled trials (RCTs) published between 2013-January 2018 which compared carboplatin and cisplatin combined with: gemcitabine, vinorelbine, docetaxel, paclitaxel, irinotecan, or pemetrexed. Endpoints included overall survival (OS), one-year OS, objective response rate (ORR), grade 3/4 drug-related toxicities, and HRQoL. RESULTS: Twelve RCTs (2,048 patients) were identified from 4,139 records for inclusion in the meta-analysis. There were no significant differences in OS (hazards ratio [HR]: 1.08, 95% confidence interval [CI]: 0.96, 1.21) and one-year OS (relative risk [RR]: 0.97, CI: 0.89, 1.07) between carboplatin- and cisplatin-based chemotherapy. A small effect on ORR favouring cisplatin was detected (RR = 0.88; CI: 0.78, 0.99). Differences in drug-related toxicities were observed between carboplatin- and cisplatin-based chemotherapy for thrombocytopenia, anaemia, neurotoxicity, and the risk of nausea/vomiting. Three RCTs comparing HRQoL between carboplatin- and cisplatin-based chemotherapy found no significant differences. CONCLUSIONS: This updated evidence base corroborates findings of previous meta-analyses showing no difference in OS between carboplatin- and cisplatin-based chemotherapy, despite a slight benefit in ORR for cisplatin. Toxicity profiles should be considered alongside patients' comorbidities in the choice of therapy.

Characteristics of non-randomised studies using comparisons with external controls submitted for regulatory approval in the USA and Europe: a systematic review.

OBJECTIVES: Non-randomised clinical trial designs involving comparisons against external controls or specific standards can be used to support regulatory submissions for indications in diseases that are rare, with high unmet need, without approved therapies and/or where placebo is considered unethical. The objective of this review was to summarise the characteristics of non-randomised trials submitted to the European Medicines Agency (EMA) or Food and Drug Administration (FDA) for indications in haematological cancers, haematological non-malignant conditions, stem cell transplants or rare metabolic diseases. METHODS: We conducted systematic searches of EMA databases of conditional approvals, exceptional circumstances, or orphan drug designations and FDA inventories of orphan drug designations, accelerated approvals, breakthrough therapy, fast-track and priority approvals. Products were included if reviewed by at least one agency between 2005 and 2017, the primary evidence base was non-randomised trial(s) and the indication was for haematological cancers, stem cell transplantation, haematological conditions or rare metabolic conditions. RESULTS: We identified 43 eligible indication-specific products using non-randomised study designs involving comparisons with external controls, submitted to the EMA (n=34) and/or FDA (n=41). Of the 43 indication-specific products, 4 involved matching external controls to the population of a non-randomised interventional study using individual patient-level data (IPD), 12 referred to external controls without IPD and 27 did not explicitly reference external controls. The FDA approved 98% of submissions, with 56% accelerated approvals; most required postapproval confirmatory randomised controlled trials (RCT). The EMA approved 79% of submissions, with a quarter of approvals conditional on completion of a postapproval RCT or additional non-randomised trials. CONCLUSIONS: There has been a large increase in submissions to the EMA and FDA using non-randomised study designs involving comparisons with external controls in recent years. This study demonstrated that regulators may be willing to approve such submissions, although approvals are often conditional on further confirmatory evidence from postapproval studies.

Health-Related Quality of Life of Patients with Acute Myeloid Leukemia: A Systematic Literature Review.

INTRODUCTION: Patients with acute myeloid leukemia (AML), especially those with relapsed or refractory AML, have poor clinical prognosis and outcomes. Health-related quality of life (HRQoL) assessments have become increasingly important in oncology, aiding in identifying and informing supportive therapy needs during treatment and beyond; however, HRQoL in hematology, and AML in particular, has received relatively minor attention. The aim was to identify and summarize estimates of HRQoL in patients with AML, including patients with relapsed or refractory AML. METHODS: A systematic literature review was performed. MEDLINE and EMBASE databases were searched for peer-reviewed literature published between 2004 and 2014 in the US and Europe. Abstracts from four relevant conference proceedings between 2012 and 2014 were reviewed. Data from eligible studies were extracted describing the HRQoL instruments used, domains assessed, and HRQoL scores reported. RESULTS: Fourteen peer-reviewed studies met the eligibility criteria and were included in the review. Cancer- or leukemia-specific HRQoL measures were used in 78.6% of the studies. Overall, HRQoL was superior among AML survivors compared to individuals on active treatment. Fatigue was identified as the most problematic symptom domain in patients, irrespective of their treatment status. Reported HRQoL declined shortly after diagnosis or treatment initiation and recovered over time. CONCLUSION: The included studies identified a decrease in HRQoL after treatment initiation and highlighted the role of fatigue in HRQoL in this patient population. Limited HRQoL data were identified among relapsed or refractory AML patients although they have worse prognostic outcomes. New treatment options that have less negative impact on HRQoL or health initiatives specifically targeting HRQoL of patients with AML are warranted. In addition, further studies exploring HRQoL in the relapsed or refractory patient population are needed to inform disease management and treatment decisions.

Glucagon-like peptide-1 receptor agonists compared with basal insulins for the treatment of type 2 diabetes mellitus: a systematic review and meta-analysis.

AIMS: Since 2005, several glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been approved to treat people with type 2 diabetes. These agents are considered for use at the same point in the treatment paradigm as basal insulins. A comprehensive comparison of these drug classes, therefore, can help inform treatment decisions. This systematic review and meta-analysis assessed the clinical efficacy and safety of GLP-1 RAs compared with basal insulins. MATERIALS AND METHODS: MEDLINE, EMBASE, CENTRAL and PubMed databases were searched. Randomized clinical trials (RCTs) of ≥16 weeks' duration comparing GLP-1 RAs vs basal insulins in adults with type 2 diabetes inadequately controlled with oral antihyperglycemic drugs were included. Data on the change from baseline to 26 weeks (±10 weeks) of treatment in hemoglobin A1c (HbA1c) and weight, as well as the proportion of patients experiencing hypoglycaemia, were extracted. Fixed-effect pairwise meta-analyses were conducted where data were available from ≥2 studies. RESULTS: Fifteen RCTs were identified and 11 were meta-analysed. The once-weekly GLP-1 RAs, exenatide long acting release (LAR) and dulaglutide, led to greater, statistically significant mean HbA1c reductions vs basal insulins (exenatide: -0.31% [95% confidence interval -0.42, -0.19], dulaglutide: -0.39% [-0.49, -0.29]) whilst once-daily liraglutide and twice-daily exenatide did not (liraglutide: 0.06% [-0.06, 0.18], exenatide: 0.01% [-0.11, 0.13]). Mean weight reduction was seen with all GLP-1 RAs while mean weight gain was seen with basal insulins. Interpretation of the analysis of hypoglycaemia was limited by inconsistent definitions and reporting. Because of the limited number of available studies sensitivity analyses to explore heterogeneity could not be conducted. CONCLUSIONS: Although weight reduction is seen with all GLP-1 RA's, only the once-weekly agents, exenatide LAR and dulaglutide, demonstrate significant HbA1c reductions when compared to basal insulins.

Quality of Care for Patients with Type 2 Diabetes Mellitus in Dubai: A HEDIS-Like Assessment.

Objective. As little data are available on the quality of type 2 diabetes mellitus (T2DM) care in the Arabian Gulf States, we estimated the proportion of patients receiving recommended monitoring at the Dubai Hospital for T2DM over one year. Methods. Charts from 150 adults with T2DM were systematically sampled and quality of care was assessed during one calendar year, using a Healthcare Effectiveness Data and Information Set- (HEDIS-) like assessment. Screening for glycosylated haemoglobin (HbA1c), low-density lipoprotein (LDL), blood pressure, retinopathy, and nephropathy was considered. Patients were classified based on their most recent test in the period, and predictors of receiving quality care were examined. Results. Mean age was 58 years (standard deviation (SD): 12.4 years) and 33% were males. Over the year, 98% underwent HbA1c screening (50% had control and 28% displayed poor control); 91% underwent LDL screening (65% had control); 55% had blood pressure control; 30% had retinopathy screening; and 22% received attention for nephropathy. No individual characteristics examined predicted receiving quality care. Conclusion. Some guideline monitoring was conducted for most patients; and rates of monitoring for selected measures were comparable to benchmarks from the United States. Greater understanding of factors leading to high adherence would be useful for other areas of preventive care and other jurisdictions.

The economic burden of prematurity in Canada.

BACKGROUND: Preterm birth is a major risk factor for morbidity and mortality among infants worldwide, and imposes considerable burden on health, education and social services, as well as on families and caregivers. Morbidity and mortality resulting from preterm birth is highest among early (< 28 weeks gestational age) and moderate (28-32 weeks) preterm infants, relative to late preterm infants (33-36 weeks). However, substantial societal burden is associated with late prematurity due to the larger number of late preterm infants relative to early and moderate preterm infants. METHODS: The aim in this study was to characterize the burden of premature birth in Canada for early, moderate, and late premature infants, including resource utilization, direct medical costs, parental out-of-pocket costs, education costs, and mortality, using a validated and published decision model from the UK, and adapting it to a Canadian setting based on analysis of administrative, population-based data from Québec. RESULTS: Two-year survival was estimated at 56.0% for early preterm infants, 92.8% for moderate preterm infants, and 98.4% for late preterm infants. Per infant resource utilization consistently decreased with age. For moderately preterm infants, hospital days ranged from 1.6 at age two to 0.09 at age ten. Cost per infant over the first ten years of life was estimated to be $67,467 for early preterm infants, $52,796 for moderate preterm infants, and $10,010 for late preterm infants. Based on population sizes this corresponds to total national costs of $123.3 million for early preterm infants, $255.6 million for moderate preterm infants, $208.2 million for late preterm infants, and $587.1 million for all infants. CONCLUSION: Premature birth results in significant infant morbidity, mortality, healthcare utilization and costs in Canada. A comprehensive decision-model based on analysis of a Canadian population-based administrative data source suggested that the greatest national-level burden is associated with moderate preterm infants due to both a large cost per infant and population size while the highest individual-level burden is in early preterm infants and the largest total population size is in late preterm infants. Although the highest medical costs are incurred during the neonatal period, greater resource utilization and costs extend into childhood.

A population-based study of childhood respiratory morbidity after severe lower respiratory tract infections in early childhood.

OBJECTIVES: To estimate the risk of childhood chronic respiratory morbidity among those hospitalized for severe lower respiratory tract infection (LRTI) in early childhood, and to determine whether severe LRTI is an independent predictor. STUDY DESIGN: The population-based Régie de l'Assurance Maladie du Québec datasets were used to identify LRTI hospitalizations before age 2 years in a birth cohort from 1996-1997 and a comparison cohort of children without an LRTI hospitalization. The incidence rate and incidence rate ratio of chronic respiratory morbidity before age 10 years were calculated, and multivariable logistic regression was performed to estimate the impact of LRTI hospitalization on chronic respiratory morbidity. Population-attributable risks of chronic respiratory morbidity due to severe LRTI were estimated, and similar analyses were performed for respiratory syncytial virus LRTI. RESULTS: Among the birth cohort, 7104 patients (4.9%) were hospitalized for LRTI before age 2 years. By age 10 years, 52.5% of the LRTI cohort and 27.9% of the nonhospitalized cohort had developed chronic respiratory morbidity; the incidence rate ratio was 1.81 (95% CI, 1.76-1.86) for males and 1.91 (95% CI, 1.84-1.99) for females. The OR for chronic respiratory morbidity based on LRTI hospitalization before age 2 years was 2.79 (95% CI, 2.66-2.93). The population-attributable risk of chronic respiratory morbidity due to any LRTI was approximately 25%, and that for respiratory syncytial virus LRTI was similar. CONCLUSIONS: Hospitalization of young children for LRTIs is associated with two-fold increased risk of childhood chronic respiratory morbidity, demonstrating the ongoing impact of LRTI in infancy.

A systematic review of risk factors associated with surgical site infections among surgical patients.

IMPORTANCE: Surgical site infection (SSI) complicates 2-5% of surgeries in the United States. Severity of SSI ranges from superficial skin infection to life-threatening conditions such as severe sepsis, and SSIs are responsible for increased morbidity, mortality, and economic burden associated with surgery. Staphylococcus aureus (S. aureus) is a commonly-isolated organism for SSI, and methicillin-resistant S. aureus SSI incidence is increasing globally. OBJECTIVE: The objective of this systematic review was to characterize risk factors for SSI within observational studies describing incidence of SSI in a real-world setting. EVIDENCE REVIEW: An initial search identified 328 titles published in 2002-2012; 57 were identified as relevant for data extraction. Extracted information included study design and methodology, reported cumulative incidence and post-surgical time until onset of SSI, and odds ratios and associated variability for all factors considered in univariate and/or multivariable analyses. FINDINGS: Median SSI incidence was 3.7%, ranging from 0.1% to 50.4%. Incidence of overall SSI and S. aureus SSI were both highest in tumor-related and transplant surgeries. Median time until SSI onset was 17.0 days, with longer time-to-onset for orthopedic and transplant surgeries. Risk factors consistently identified as associated with SSI included co-morbidities, advanced age, risk indices, patient frailty, and surgery complexity. Thirteen studies considered diabetes as a risk factor in multivariable analysis; 85% found a significant association with SSI, with odds ratios ranging from 1.5-24.3. Longer surgeries were associated with increased SSI risk, with a median odds ratio of 2.3 across 11 studies reporting significant results. CONCLUSIONS AND RELEVANCE: In a broad review of published literature, risk factors for SSI were characterized as describing reduced fitness, patient frailty, surgery duration, and complexity. Recognition of risk factors frequently associated with SSI allows for identification of such patients with the greatest need for optimal preventive measures to be identified and pre-treatment prior to surgery.

Respiratory distress syndrome at birth is a risk factor for hospitalization for lower respiratory tract infections in infancy.

BACKGROUND: Respiratory distress syndrome (RDS) and hospitalization for lower respiratory tract infection (LRTI; specifically, respiratory syncytial virus) are important causes of morbidity in infancy. Whether RDS at birth is an independent risk factor for LRTI is unknown. This study estimated the risk of LRTI-related hospitalization among late preterm infants with a history of RDS. METHODS: The population-based cohort from Québec included all late preterm infants (32-36 weeks gestational age) born in 1996 to 1997. RDS was identified by International Classification of Diseases, Ninth Revision code 769, and a comparison cohort generated from all without RDS. A multivariable model estimated the adjusted odds ratio of LRTI-related hospitalization among late preterm infants with a history of RDS; and the incidence and increased risk of childhood chronic respiratory morbidity was calculated. RESULTS: Of the 7488 late preterms, 459 (6.1%) had a history of RDS; 525 late preterms (7.0%) were hospitalized for LRTI in infancy, including 57 (12.4%) with RDS. The adjusted odds ratio for LRTI-related hospitalization associated with RDS was 1.6 (1.2-2.2). Other significant risk factors included male sex, or diagnosis of other respiratory conditions, diaphragm anomalies, bacteremia, intraventricular hemorrhage, congenital heart disease or respiratory system anomalies. Late preterm infants with a history of RDS were also at a significantly increased risk of childhood chronic respiratory morbidity. CONCLUSIONS: Late preterms with a history of RDS are at a 60% increased risk of LRTI-related hospitalization in infancy compared with late preterm infants without RDS. Such infants may benefit from interventions decreasing the risk of contracting respiratory viruses causing acute LRTI.