Evaluating a Real World Ban on Menthol Cigarettes: An Interrupted Time-Series Analysis of Sales.

BACKGROUND: Menthol in cigarettes has been shown to increase regular cigarette smoking and nicotine dependence, and decrease success in smoking cessation. Owing to these reasons, in May 2015, the province of Ontario introduced a menthol ban on tobacco products that came into effect in January 2017 prior to a Federal Canadian Ban in October 2017. The objective of this article was to assess the effect of a provincial menthol ban on cigarette wholesale sales in Ontario. METHODS: Wholesale data submitted by tobacco manufacturers to Health Canada pursuant to the federal Tobacco Reporting Regulations from October 2012 to September 2017 were analyzed using interrupted time-series analysis. Changes in sales of cigarettes with and without menthol were estimated, using the province of British Columbia as a comparison. Analyses were seasonally adjusted. RESULTS: Sales of menthol and nonmenthol cigarettes increased from 2013 until the implementation of the 2017 provincial ban. Subsequently, a sharp decline of 55 million menthol cigarettes and 128 million total cigarettes was observed in Ontario. As a comparison, no significant changes were observed in British Columbia. CONCLUSION: This study supports the conclusion that implementation of a menthol ban in Ontario was associated with significant reduction of menthol cigarette sales and total cigarettes sales, compared to British Columbia where there was no provincial menthol ban. This suggests that menthol regulations in jurisdictions with a larger percentage of menthol smokers are likely to be highly effective. IMPLICATIONS: The 2017 menthol ban was associated with significant reduction of menthol cigarette sales and total cigarette sales suggesting that menthol regulations will have important effects on cigarette consumption.

Association of flavoured cigar regulations with wholesale tobacco volumes in Canada: an interrupted time series analysis.

INTRODUCTION: This study examines the association of Federal Canadian regulations passed in 2009 addressing flavours (excluding menthol) in small cigars with changes in cigar sales. METHODS: Quarterly wholesale unit data as reported to Health Canada from 2001 through 2016 were analysed using interrupted time series analysis. Changes in sales of cigars with and without flavour descriptors were estimated. Analyses were seasonally adjusted. Changes in the flavour types were assessed over time. RESULTS: The Federal flavour regulations were associated with a reduction in the sales of flavoured cigars by 59 million units (95% CI -86.0 to -32.4). Increases in sales of cigars with descriptors other than flavours (eg, colour or other ambiguous terms) were observed (9.6 million increase (95% CI -1.3 to 20.5), but the overall level (decline of 49.6 million units (95% CI -73.5 to -25.8) and trend of sales of cigars (6.9 million units per quarter (95% CI -8.1 to -5.7)) declined following the ban. Sensitivity analysis showed that there was no substantial difference in effect over time comparing Ontario and British Columbia, suggesting that other provincial tobacco control legislation was not associated with the changes in levels. Analyses suggested that the level change was sensitive to the specification of the date. CONCLUSION: This study demonstrates that flavour regulations have the potential to substantially impact tobacco sales. However, exemptions for certain flavours and product types may have reduced the effectiveness of the ban, indicating the need for comprehensive, well-designed regulations.

Rotator cuff repair: a review of surgical techniques, animal models, and new technologies under development.

Rotator cuff tears are the most common musculoskeletal injury occurring in the shoulder. Current surgical repair fails to heal in 20% to 95% of patients, depending on age, size of the tear, smoking, time of repair, tendon quality, muscle quality, healing response, and surgical treatments. These problems are worsened by the limited healing potential of injured tendons attributed to the presence of degenerative changes and relatively poor vascularity of the cuff tendons. Development of new techniques to treat rotator cuff tears requires testing in animal models to assess safety and efficacy before clinical testing. Hence, it is important to evaluate appropriate animal models for rotator cuff research with degeneration of tendons, muscular atrophy, and fatty infiltration similar to humans. This report reviews current clinical treatments and preclinical approaches for rotator cuff tear repair. The review will focus on current clinical surgical treatments, new repair strategies under clinical and preclinical development, and will also describe different animal models available for rotator cuff research. These findings and future directions for rotator cuff tear repair will be discussed.

Freeze-dried chitosan-platelet-rich plasma implants improve supraspinatus tendon attachment in a transosseous rotator cuff repair model in the rabbit.

Rotator cuff tears result in shoulder pain, stiffness, weakness and loss of motion. After surgical repair, high failure rates have been reported based on objective imaging and it is recognized that current surgical treatments need improvement. The aim of the study was to assess whether implants composed of freeze-dried chitosan (CS) solubilized in autologous platelet-rich plasma (PRP) can improve rotator cuff repair in a rabbit model. Complete tears were created bilaterally in the supraspinatus tendon of New Zealand White rabbits ( n = 4 in a pilot feasibility study followed by n = 13 in a larger efficacy study), which were repaired using transosseous suturing. On the treated side, CS-PRP implants were injected into the transosseous tunnels and the tendon itself, and healing was assessed histologically at time points ranging from one day to two months post-surgery. CS-PRP implants were resident within transosseous tunnels and adhered to tendon surfaces at one day post-surgery and induced recruitment of polymorphonuclear cells from 1 to 14 days. CS-PRP implants improved attachment of the supraspinatus tendon to the humeral head through increased bone remodelling at the greater tuberosity and also inhibited heterotopic ossification of the supraspinatus tendon at two months. In addition, the implants did not induce any detectable deleterious effects. This preliminary study provides the first evidence that CS-PRP implants could be effective in improving rotator cuff tendon attachment in a small animal model.

Freeze-Dried Chitosan-Platelet-Rich Plasma Implants for Rotator Cuff Tear Repair: Pilot Ovine Studies.

Rotator cuff tears are a very common shoulder pathology. Different suturing techniques have been used for surgical cuff repair, but failure of healing remains a significant clinical challenge. The objective of this study was to establish and compare chronic and acute ovine rotator cuff tear models in our laboratory and investigate the feasibility of using chitosan (CS)-platelet-rich plasma (PRP) implants in conjunction with suture anchors to treat rotator cuff tears in large animal models. Repair with suture anchors only was used as control. In two preliminary pilot studies, unilateral full-thickness tears were created in the infraspinatus (ISP) tendon of mature female Texel-cross sheep. In the chronic model (n = 4 sheep), the tendons were capped with silicon and allowed to retract for 6 weeks, leading to degenerative changes, whereas the tendons were immediately repaired in the acute model (n = 4 sheep). Transected ISP tendons were reattached with suture anchors and, in the case of treated shoulders, implants composed of freeze-dried CS solubilized in autologous PRP were additionally applied to the tendon-bone interface and on top of the repaired site. The chronic defect model induced significant tendon degeneration and retraction, which made repair more challenging than in the acute defect model. Half the tendons in the chronic repair model were found to be irrepairable at 6 weeks. In the other half, the tendons could not be reattached to the footprint due to significant retraction, which made this a model of tissue formation in a gap. In contrast, the acute tendon repair model was executed easily. Extensive bone remodeling and tissue ingrowth at the tendon-bone interface were observed in the case of treatment with anchors + CS-PRP in both models, suggesting that CS-PRP implants could potentially modulate rotator cuff healing processes in large animal models.

Chitosan inhibits platelet-mediated clot retraction, increases platelet-derived growth factor release, and increases residence time and bioactivity of platelet-rich plasma in vivo.

Platelet-rich plasma (PRP) has been used to treat different orthopedic conditions, however, the clinical benefits of using PRP remain uncertain. Chitosan (CS)-PRP implants have been shown to improve meniscus, rotator cuff and cartilage repair in pre-clinical models. The purpose of this current study was to investigate in vitro and in vivo mechanisms of action of CS-PRP implants. Freeze-dried formulations containing 1% (w/v) CS (80% degree of deacetylation and number average molar mass 38 kDa), 1% (w/v) trehalose as a lyoprotectant and 42.2 mM calcium chloride as a clot activator were solubilized in PRP. Gravimetric measurements and molecular/cellular imaging studies revealed that clot retraction is inhibited in CS-PRP hybrid clots through physical coating of platelets, blood cells and fibrin strands by chitosan, which interferes with platelet aggregation and platelet-mediated clot retraction. Flow cytometry and ELISA assays revealed that platelets are activated and granules secreted in CS-PRP hybrid clots and that cumulative release of platelet-derived growth factor (PDGF-AB) and epidermal growth factor is higher from CS-PRP hybrid clots compared to PRP clots in vitro. Finally, CS-PRP implants resided for up to 6 weeks in a subcutaneous implantation model and induced cell recruitment and granulation tissue synthesis, confirming greater residency and bioactivity compared to PRP in vivo.