Uptake and characteristics of zoledronic acid and denosumab patients and physicians in Ontario, Canada: impact of drug formulary access.

UNLABELLED: The addition of Limited Use criteria (less restrictive access) for zoledronic acid resulted in an immediate and significant increase in uptake and resulted in differences in patient/physician characteristics. In comparison, the uptake of denosumab (only listed with Limited Use) was rapid. Thus, formulary access restrictions have significant implications for prescribing. INTRODUCTION: We sought to describe the use of zoledronic acid and denosumab by physicians and patients over time and examine the impact of a 2012 provincial formulary modification that removed the administrative burden on physicians when prescribing zoledronic acid. METHODS: We identified users of zoledronic acid and denosumab using Ontario pharmacy claims data. The number of new patients and physicians was plotted and examined over time. Interrupted time series analysis examined the impact of a formulary modification to zoledronic acid use and prescribing. Descriptive characteristics of patients and prescribers were summarized pre- and post-formulary modification for zoledronic acid and overall for denosumab. RESULTS: We identified 1463 zoledronic acid patients treated by 627 physicians and 16,736 denosumab patients treated by 2904 physicians. In the first 2 months on the market, we identified a rapid uptake of denosumab (>450 physicians and >1200 patients) in contrast to zoledronic acid (<10 physicians and <10 patients). Zoledronic acid use increased significantly in the 2-month post-formulary change, yet no change in denosumab was observed. Prior to the formulary modification, more zoledronic acid patients had a history of osteoporosis therapy (41 vs. 26%) or bone density testing (30 vs. 10%). Compared to zoledronic patients (post-formulary modification), more denosumab patients had prior osteoporosis therapy (55 vs. 26%), yet fewer had a gastrointestinal diagnosis (6 vs. 11%). CONCLUSION: We identified a rapid uptake of denosumab in only 15 months of observation. A provincial formulary modification to zoledronic acid resulted in an increase in utilization and impacted patient characteristics.

Is the emergency department an appropriate substitute for primary care for persons with traumatic spinal cord injury?

STUDY DESIGN: Retrospective cohort with linkage of administrative data sets. OBJECTIVES: To describe the patterns (for example, number of visits by year post-injury) and characteristics of the emergency department (ED) visits (for example, acuity level, timing of visits, reasons for visits) made by persons with traumatic spinal cord injury (TSCI) over a 6-year period following injury. SETTINGS: Ontario, Canada. METHODS: Rates of ED utilization and reasons for ED visits were calculated between the fiscal years 2003-2009. Reasons for visits were categorized by acuity level: potentially preventable visits were defined as visits related to ambulatory sensitive conditions; low acuity and high acuity visits were defined by the Canadian Triage and Acuity Scale. RESULTS: The total number of ED visits for the 6-year period is 4403 (n=1217). Of these visits, 752 (17%) were classified as potentially preventable, 1443 (33%) as low acuity and 2208 (50%) as high acuity. The majority of patients, regardless of acuity level, did not see a primary care practitioner on the day of the ED visit and most visits occurred during the weekday (Mon-Fri 0700-1659 hours). ED use was highest in the first year but remained high over the subsequent years. For potentially preventable visits, the majority of visits were related to urinary tract infections (n=385 visits, 51.2%), followed by pneumonia (n=91, 12.1%). CONCLUSION: Given the high rates of ED use for low acuity and potentially preventable conditions, these results suggest that the ED is being used as an inappropriate substitute for primary care for individuals with TSCI 50% of the time.

Associative bacteria influence maize (Zea mays L.) growth, physiology and root anatomy under different nitrogen levels.

Despite the great diversity of plant growth-promoting bacteria (PGPB) with potential to partially replace the use of N fertilisers in agriculture, few PGPB have been explored for the production of commercial inoculants, reinforcing the importance of identifying positive plant-bacteria interactions. Aiming to better understand the influence of PGPB inoculation in plant development, two PGPB species with distant phylogenetic relationship were inoculated in maize. Maize seeds were inoculated with Bacillus sp. or Azospirillum brasilense. After germination, the plants were subjected to two N treatments: full (N+) and limiting (N-) N supply. Then, anatomical, biometric and physiological analyses were performed. Both PGPB species modified the anatomical pattern of roots, as verified by the higher metaxylem vessel element (MVE) number. Bacillus sp. also increased the MVE area in maize roots. Under N+ conditions, both PGPB decreased leaf protein content and led to development of shorter roots; however, Bacillus sp. increased root and shoot dry weight, whereas A. brasilense increased photosynthesis rate and leaf nitrate content. In plants subjected to N limitation (N-), photosynthesis rate and photosystem II efficiency increased in maize inoculated with Bacillus sp., whilst A. brasilense contained higher ammonium, amino acids and total soluble sugars in leaves, compared to the control. Plant developmental and metabolical patterns were switched by the inoculation, regardless of the inoculant bacterium used, producing similar as well as distinct modifications to the parameters studied. These results indicate that even non-diazotrophic inoculant strains can improve the plant N status as result of the morpho-anatomical and physiological modifications produced by the PGPB.

Acclimation responses to high light by Guazuma ulmifolia Lam. (Malvaceae) leaves at different stages of development.

The re-composition of deforested environments requires the prior acclimation of seedlings to full sun in nurseries. Seedlings can overcome excess light either through the acclimation of pre-existing fully expanded leaves or through the development of new leaves that are acclimated to the new light environment. Here, we compared the acclimation capacity of mature (MatL, fully expanded at the time of transfer) and newly expanded (NewL, expanded after the light shift) leaves of Guazuma ulmifolia Lam. (Malvaceae) seedlings to high light. The seedlings were initially grown under shade and then transferred to full sunlight. MatL and NewL were used for chlorophyll fluorescence and gas exchange analyses, pigment extraction and morpho-anatomical measurements. After the transfer of seedlings to full sun, the MatL persisted and acclimated to some extent to the new light condition, since they underwent alterations in some morpho-physiological traits and maintained a functional electron transport chain and positive net photosynthesis rate. However, long-term exposure to high light led to chronic photoinhibition in MatL, which could be related to the limited plasticity of leaf morpho-anatomical attributes. However, the NewL showed a high capacity to use the absorbed energy in photochemistry and dissipate excess energy harmlessly, attributes that were favoured by the high structural plasticity exhibited by these leaves. Both the maintenance of mature, photosynthetically active leaves and the production of new leaves with a high capacity to cope with excess energy were important for acclimation of G. ulmifolia seedlings.

Prevalence and possible mechanisms of ventricular arrhythmias in athletes.

To investigate the prevalence and nature of ventricular arrhythmias in athletes, 40 well trained healthy endurance athletes (20 cyclists and 20 runners) and 40 healthy sedentary subjects as controls were studied. Twenty four-hour continuous ECG monitoring showed a higher, even though not significant prevalence of ventricular ectopy in athletes (70% vs 55%). Complex forms of ventricular ectopy were also more prevalent in the athletes than in the controls (25% vs 5%; p less than 0.05). A prolongation of both measured QT interval and QT corrected for heart rate was observed at the ECG. Echocardiograms showed higher dimensional indices in the athletes, while functional indices were similar in athletes and controls. No correlation was found between any ECG or echocardiographic finding and the grade of ventricular arrhythmia. The comparison between the cyclists and the runners did not show any significant difference in the prevalence of ventricular arrhythmias or in the QT interval duration.

[Incidence of aortic recoarctation in 161 patients after a mean follow-up of 8 years. The usefulness of pressure gradient measurement at rest and following exercise and of digital angiography]. / Incidenza di ricoartazione aortica in 161 pazienti dopo un follow-up medio di 8 anni. Utilità della misurazione dei gradienti pressori a riposo e dopo sforzo e dell'angiografia digitale.

The incidence of aortic recoarctation has been evaluated after a mean follow-up period of 8.2 years in 161 patients aged from 2 to 54 years at the time of the operation. To this aim, blood pressure levels in the upper and lower limbs were measured at rest and after bicycle ergometer exercise. Patients whose systolic pressure gradient was significant (either above 20 mmHg at rest or 35 mmHg after exercise) underwent aortic digital angiography. Aortic coarctation was diagnosed when the ratio of the aortic area at the site of the operation was less than 40% of that at diaphragmatic level (Frederiksen's index III). Thus the overall incidence of recoarctation was 10.1%. All patients with a significant gradient at rest also showed a significant gradient after exercise. This suggests that it is worthwhile performing digital angiography directly, without exercise testing, in these patients. However, 39.8% of the patients without significant rest gradients displayed a significant gradient after exercise. On the whole, only 21.4% of the patients with a significant gradient after exercise had signs of recoarctation on digital angiography.

Effect of endurance training on Q-T interval and cardiac electrical stability in boys aged 10 to 14. Ventricular arrhythmias in trained boys.

In 30 highly trained boys aged 10-14 the prevalence of ventricular ectopic beats and Q-T interval duration were studied. In trained boys ECG Holter monitoring showed a higher even though not significantly different prevalence of ventricular arrhythmias than in 30 age-matched untrained controls. Ventricular ectopy was on the contrary lower than in a group of 30 adult athletes. Q-T corrected (Q-Tc) interval in the trained boys was longer than in the sedentary controls (p less than 0.001), while it was as long as in the adult athletes. No correlation was found between the degree of severity of ventricular ectopic beats and Q-Tc interval duration, heart rate or echocardiographic dimensional and functional findings. The clinical and prognostic importance of complex ventricular arrhythmias detected in healthy athletes remains to be elucidated.