Limited low-quality evidence of a non-statistically significant trend toward smoking cessation in adults using nicotine e-cigarettes exists compared with other therapies or placebo. Larger, high-quality studies are needed to inform policy decisions.

C lavicle fractures are common injuries, affecting about 22 000 Canadians each year and numbering 1.75 million fractures worldwide. [1][2][3][4][5][6] The majority of these fractures are located in the midshaft, accounting for about 80% of all clavicle fractures.1,2 Closed midshaft fractures were traditionally treated nonoperatively, a practice largely based on previous studies by Neer and Rowe. 7,8 In the last decade, evidence challenged the standard of nonoperative treatment, reporting high rates of nonunion (15%-20%), poor early function, and residual sequelae at 6 months following nonoperative management in up to 42% of patients.9 Small clinical trials that followed have fuelled a growing popularity to treat these fractures surgically with plates and screws or intramedullary devices; however, these procedures carry inherent surgical risks for infection, implant failure and hardware irritation requiring subsequent removal. 10,11 Whether surgery or a conservative approach is the optimal method of management for midshaft clavicle fractures is still an issue of debate. Several trials have compared operative and nonoperative approaches to treatment. In the last 5 years, a number of trials have also investigated various surgical techniques and the use of different implants. Previous reviews focused only on the operative versus nonoperative debate. 1,9,11,12 Our review adds to this body of literature by providing data from the largest and most recent trial. It also provides a summary of the evidence on surgical techniques for these injuries, as well as nonsurgical options.We performed a meta-analysis to determine the effect of operative and nonoperative interventions for treating acute displaced midshaft clavicle fractures on the risk of secondary operation and all complications and on long-term function. Background: The popularity of surgery for acute displaced midshaft clavicle fractures has been fuelled by early randomized controlled trials (RCTs) showing improved rates of radiographic union and perceived functional benefits compared with nonoperative approaches. We performed a meta-analysis to determine the effect of operative and nonoperative interventions on the risk of secondary operation and complications and on long-term function. Operative versus nonoperative interventions for common

BackgroundSurrogate outcomes are a significant challenge in drug evaluation for health technology assessment (HTA) agencies. The research objectives were to: identify factors associated with surrogate use and acceptability in Canada’s Common Drug Review (CDR) recommendations, and compare the CDR with other HTA or regulatory agencies regarding surrogate concerns.MethodsFinal recommendations were identified from CDR inception (September 2003) to December 31, 2010. Recommendations were classified by type of outcome (surrogate, final, other) and acceptability of surrogates (determined by the presence/absence of statements of concern regarding surrogates). Descriptive and statistical analyses examined factors related to surrogate use and acceptability. For thirteen surrogate-based submissions, recommendations from international HTA and regulatory agencies were reviewed for statements about surrogate acceptability.ResultsOf 156 final recommendations, 68 (44%) involved surrogates. The overall ‘do not list’ (DNL) rate was 48%; the DNL rate for surrogates was 41% (p = 0.175). The DNL rate was 64% for non-accepted surrogates (n = 28) versus 25% for accepted surrogates (odds ratio 5.4, p = 0.002). Clinical uncertainty, use of economic evidence over price alone, and a premium price were significantly associated with non-accepted surrogates. Surrogates were used most commonly for HIV, diabetes, rare diseases, cardiovascular disease and cancer. For the subset of drugs studied, other HTA agencies did not express concerns for most recommendations, while regulatory agencies frequently stated surrogate acceptance.ConclusionsThe majority of surrogates were accepted at the CDR. Non-accepted surrogates were significantly associated with clinical uncertainty and a DNL recommendation. There was inconsistency of surrogate acceptability across several international agencies. Stakeholders should consider collaboratively establishing guidelines on the use, validation, and acceptability of surrogates.

Lorlatinib is the only targeted therapy approved in Canada to treat patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) whose tumor has progressed despite treatment with second-generation ALK tyrosine kinase inhibitor (TKI), a patient population with high unmet need and lack of publicly reimbursed targeted treatments in Canada. We prospectively examined the real-world effectiveness and impact of lorlatinib on quality-of-life in 59 lorlatinib-treated patients, characterized as: median age of 62.0 years; 47.5% were female; 32.2% had central nervous system metastases; 50.8% had 2+ prior ALK TKI lines; and alectinib was the most common ALK TKI (72.9%) administered before lorlatinib, including 44.1% who received first-line alectinib. With a median follow-up of 15.3 months (IQR: 6.2–19.2), median time-to-treatment discontinuation of lorlatinib was 15.3 months (95% CI: 7.9–not reached), with 54.2% (95% CI: 40.8–65.9%) of patients without treatment discontinuation at 12 months. At baseline, the mean health utility score (HUS) was 0.744 (SD: 0.200). At 3 months, patients receiving lorlatinib demonstrated a 0.069 (95% CI: 0.020–0.118; p = 0.007) average HUS increase over baseline; HUS was maintained at 6 and 12 months. Thus, patients with ALK-positive NSCLC post second-generation ALK TKI remained on lorlatinib for a meaningful duration of time while their quality-of-life was preserved.