Adherence to and persistence with antidiabetic medications and associations with clinical and economic outcomes in people with type 2 diabetes mellitus: A systematic literature review

We designed a systematic literature review to identify available evidence on adherence to and persistence with antidiabetic medication in people with type 2 diabetes (T2D). Electronic screening and congress searches identified real-world noninterventional studies (published between 2010 and October 2020) reporting estimates of adherence to and persistence with antidiabetic medication in adults with T2D, and associations with glycaemic control, microvascular and/or macrovascular complications, hospitalizations and healthcare costs. Ninety-two relevant studies were identified, the majority of which were retrospective and reported US data. The proportions of patients considered adherent (median [range] 51.2% [9.4%-84.3%]) or persistent (median [range] 47.7% [16.9%-94.0%]) varied widely across studies. Multiple studies reported an association between greater adherence/persistence and greater reductions in glycated haemoglobin levels. Better adherence/persistence was associated with fewer microvascular and/or macrovascular outcomes, although there was little consistency across studies in terms of which outcomes were improved. More adherent and more persistent patients were typically less likely to be hospitalized or to have emergency department visits/admissions and spent fewer days in hospital annually than less adherent/persistent patients. Greater adherence and persistence were generally associated with lower hospitalization costs, higher pharmacy costs and lower or budget-neutral total healthcare costs compared with lower adherence/persistence. In conclusion, better adherence and persistence in people with T2D is associated with lower rates of microvascular and/or macrovascular outcomes and inpatient hospitalization, and lower or budget-neutral total healthcare expenditure. Education and treatment strategies to address suboptimal adherence and persistence are needed to improve clinical and economic outcomes.     

Video observation of hand-hygiene compliance in a manufacturer of ready-to-eat pie and pastry products

ABSTRACT

Food-handler hand-hygiene can be a contributory factor for food-borne illness. Cognitive data (knowledge/attitudes/self-reported practices), while informative, are not indicative of behaviour, and are subject to biases. Consequently, observation of behaviour is superior to survey data. However, researcher presence in direct observation increases reactivity, whereas video observation gives comprehensive analysis over a longer period, furthermore, familiarity reduces reactivity. Although video observation has been used to assess food safety at retail/foodservice, this valuable method is under-utilized in food-manufacturing environments. For the study, footage (24 h) was reviewed to assess compliance in a food-manufacturing site with company protocol. Video observation of food-handlers entering production (n = 674) was assessed; upon 70 occasions no attempt to implement hand-hygiene was observed. Of attempted hand-hygiene practices (n = 604), only 2% implemented compliant practices. Although 78% of attempts utilized soap, only 42% included sanitizer. Duration ranged from 1 to 69 s (Median 17 s). The study provides hand-hygiene data in an area that observational data is seldom captured.     

Cyclical strain improves artificial equine tendon constructs in vitro

Tendon injuries are a common cause of morbidity in humans. They also occur frequently in horses, and the horse provides a relevant, large animal model in which to test novel therapies. To develop novel cell therapies that can aid tendon regeneration and reduce subsequent reinjury rates, the mechanisms that control tendon tissue regeneration and matrix remodelling need to be better understood. Although a range of chemical cues have been explored (growth factors, media etc.), the influence of the mechanical environment on tendon cell culture has yet to be fully elucidated. To mimic the in vivo environment, in this study, we have utilised a novel and affordable, custom‐made bioreactor to apply a cyclical strain to tendon‐like constructs generated in three‐dimensional (3D) culture by equine tenocytes. Dynamic shear analysis (DSA), dynamic scanning calorimetry (DSC) and Fourier‐transform infrared (FTIR) spectroscopy were used to determine the mechanical and chemical properties of the resulting tendon‐like constructs. Our results demonstrate that equine tenocytes exposed to a 10% cyclical strain have an increased amount of collagen gel contraction after 7 and 8 days of culture compared with cells cultured in 3D in the absence of external strain. While all the tendon‐like constructs have a very similar chemical composition to native tendon, the application of strain improves their mechanical properties. We envisage that these results will contribute towards the development of improved biomimetic artificial tendon models for the development of novel strategies for equine regenerative therapies.     

Analysis of ordered composite endpoints

Composite endpoints are frequently used in clinical trials, but simple approaches, such as the time to first event, do not reflect any ordering among the endpoints. However, some endpoints, such as mortality, are worse than others. A variety of procedures have been proposed to reflect the severity of the individual endpoints such as pairwise ranking approaches, the win ratio, and the desirability of outcome ranking. When patients have different lengths of follow-up, however, ranking can be difficult and proposed methods do not naturally lead to regression approaches and require specialized software. This paper defines an ordering score O to operationalize the patient ranking implied by hierarchical endpoints. We show how differential right censoring of follow-up corresponds to multiple interval censoring of the ordering score allowing standard software for survival models to be used to calculate the nonparametric maximum likelihood estimators (NPMLEs) of different measures. Additionally, if one assumes that the ordering score is transformable to an exponential random variable, a semiparametric regression is obtained, which is equivalent to the proportional hazards model subject to multiple interval censoring. Standard software can be used for estimation. We show that the NPMLE can be poorly behaved compared to the simple estimators in staggered entry trials. We also show that the semiparametric estimator can be more efficient than simple estimators and explore how standard Cox regression maneuvers can be used to assess model fit, allow for flexible generalizations, and assess interactions of covariates with treatment. We analyze a trial of short versus long-term antiplatelet therapy using our methods.     

Interval breast cancer risk associations with breast density,family history and breast tissue aging

Interval breast cancers (those diagnosed between recommended mammography screens) generally have poorer outcomes and are more common among women with dense breasts. We aimed to develop a risk model for interval breast cancer. We conducted a nested case–control study within the Melbourne Collaborative Cohort Study involving 168 interval breast cancer patients and 498 matched control subjects. We measured breast density using the CUMULUS software. We recorded first-degree family history by questionnaire, measured body mass index (BMI) and calculated age-adjusted breast tissue aging, a novel measure of exposure to estrogen and progesterone based on the Pike model. We fitted conditional logistic regression to estimate odds ratio (OR) or odds ratio per adjusted standard deviation (OPERA) and calculated the area under the receiver operating characteristic curve (AUC). The stronger risk associations were for unadjusted percent breast density (OPERA = 1.99; AUC = 0.66), more so after adjusting for age and BMI (OPERA = 2.26; AUC = 0.70), and for family history (OR = 2.70; AUC = 0.56). When the latter two factors and their multiplicative interactions with age-adjusted breast tissue aging (p = 0.01 and 0.02, respectively) were fitted, the AUC was 0.73 (95% CI 0.69–0.77), equivalent to a ninefold interquartile risk ratio. In summary, compared with using dense breasts alone, risk discrimination for interval breast cancers could be doubled by instead using breast density, BMI, family history and hormonal exposure. This would also give women with dense breasts, and their physicians, more information about the major consequence of having dense breasts—an increased risk of developing an interval breast cancer.