The practical approach to the evaluation of methods used to determine the disintegration time of orally disintegrating tablets (ODTs)

Even that orodispersible tablets (ODTs) have been successfully used in therapy for more than 20 years, there is still no compendial method of their disintegration time evaluation other than the pharmacopoeial disintegration test conducted in 800–900 mL of distilled water. Therefore, several alternative tests more relevant to in vivo conditions were described by different researchers. The aim of this study was to compare these methods and correlate them with in vivo results. Six series of ODTs were prepared by direct compression. Their mechanical properties and disintegration times were measured with pharmacopoeial and alternative methods and compared with the in vivo results. The highest correlation with oral disintegration time was found in the case of own-construction apparatus with additional weight and the employment of the method proposed by Narazaki et al. The correlation coefficients were 0.9994 (p < 0.001), and 0.9907 (p < 0.001) respectively. The pharmacopoeial method correlated with the in vivo data much worse (r = 0.8925, p < 0.05). These results have shown that development of novel biorelevant methods of ODT’s disintegration time determination is eligible and scientifically justified.     

VCSim3: a VR simulator for cardiovascular interventions

Purpose

Effective and safe performance of cardiovascular interventions requires excellent catheter/guidewire manipulation skills. These skills are currently mainly gained through an apprenticeship on real patients, which may not be safe or cost-effective. Computer simulation offers an alternative for core skills training. However, replicating the physical behaviour of real instruments navigated through blood vessels is a challenging task.

Methods

We have developed VCSim3—a virtual reality simulator for cardiovascular interventions. The simulator leverages an inextensible Cosserat rod to model virtual catheters and guidewires. Their mechanical properties were optimized with respect to their real counterparts scanned in a silicone phantom using X-ray CT imaging. The instruments are manipulated via a VSP haptic device. Supporting solutions such as fluoroscopic visualization, contrast flow propagation, cardiac motion, balloon inflation, and stent deployment, enable performing a complete angioplasty procedure.

Results

We present detailed results of simulation accuracy of the virtual instruments, along with their computational performance. In addition, the results of a preliminary face and content validation study conveyed on a group of 17 interventional radiologists are given.

Conclusions

VR simulation of cardiovascular procedure can contribute to surgical training and improve the educational experience without putting patients at risk, raising ethical issues or requiring expensive animal or cadaver facilities. VCSim3 is still a prototype, yet the initial results indicate that it provides promising foundations for further development.

     

Efficacy and safety of budesonide/formoterol in the management of chronic obstructive pulmonary disease.

The efficacy and safety of budesonide/formoterol in a single inhaler compared with placebo, budesonide and formoterol were evaluated in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). In a 12-month, randomised, double-blind, placebo-controlled, parallel-group study in 812 adults (mean age 64 yrs, mean forced expiratory volume in one second (FEV1) 36% predicted normal), patients received two inhalations twice daily of either budesonide/formoterol (Symbicort) 160/4.5 microg (delivered dose), budesonide 200 microg (metered dose), formoterol 4.5 microg or placebo. Severe exacerbations and FEV1 (primary variables), peak expiratory flow (PEF), COPD symptoms, health-related quality of life (HRQL), mild exacerbations, use of reliever beta2-agonist and safety variables were recorded. Budesonide/formoterol reduced the mean number of severe exacerbations per patient per year by 24% versus placebo and 23% versus formoterol. FEV1 increased by 15% versus placebo and 9% versus budesonide. Morning PEF improved significantly on day 1 versus placebo and budesonide; after 1 week, morning PEF was improved versus placebo, budesonide and formoterol. Improvements in morning and evening PEF versus comparators were maintained over 12 months. Budesonide/formoterol decreased all symptom scores and use of reliever beta2-agonists significantly versus placebo and budesonide, and improved HRQL versus placebo. All treatments were well tolerated. These results suggest a role for budesonide/formoterol in the long-term management of moderate-to-severe chronic obstructive pulmonary disease.     

Eyeing central neurons in vascular growth and reparative angiogenesis

The generation of blood vessels is a highly synchronized process requiring the coordinated efforts of several vascular and nonvascular cell populations as well as a stringent orchestration by the tissue being vascularized. Stereotyped angiogenesis is vital for both developmental growth and to restore tissue metabolic supply after ischemic events. Central neurons such as those found in the brain, spinal cord, and retina are vast consumers of oxygen and nutrients and therefore require high rates of perfusion by functional vascular networks to ensure proper sensory transmission. During a metabolic mismatch, such as that occurring during a cerebrovascular infarct or in ischemic retinopathies, there is increasing evidence that central neurons have an inherent ability to influence the vascular response to injury. With a focus on the retina and retinal ischemic disorders, this review explores the ever-growing evidence suggesting that central neurons have the propensity to impact tissue vascularization and reparative angiogenesis. Moreover, it addresses the paradoxical ability of severely ischemic neurons to hinder vascular regrowth and thus segregate the most severely injured zones of nervous tissue. The topics covered here are pertinent for future therapeutic strategies because promoting and steering vascular growth may be beneficial for ischemic disorders.     

Measurement of active shoulder proprioception: dedicated system and device

Proprioception is an essential part of shoulder stability and neuromuscular control. The purpose of the study was the development of a precise system of shoulder proprioception assessment in the active mode (Propriometr). For that purpose, devices such as the electronic goniometer and computer software had been designed. A pilot study was carried out on a control group of 27 healthy subjects, the average age being 23.8 (22–29) in order to test the system. The result of the assessment was the finding of the error of active reproduction of the joint position (EARJP). EARJP was assessed for flexion, abduction, external and internal rotation. For every motion, reference positions were used at three different angles. The results showed EARJP to range in 3–6.1°. The proprioception evaluation system (propriometr) allows a precise measurement of active joint position sense. The designed system can be used to assess proprioception in both shoulder injuries and treatment. In addition, all achieved results of normal shoulders may serve as reference to be compared with the results of forthcoming studies.     

Clinical outcome in patients receiving systemic therapy for metastatic sarcomatoid renal cell carcinoma: A retrospective analysis☆

ObjectivesSarcomatoid metastatic renal cell carcinoma (mRCC) represents an aggressive subset of disease, and a definitive therapeutic strategy is lacking. We seek to define outcomes associated with systemic therapy (including immunotherapy, cytotoxic therapy, and targeted agents) for sarcomatoid mRCC, with attention to novel prognostic schema.Materials and methodsFrom an institutional database including 270 patients with mRCC, we identified 34 patients with documented sarcomatoid features. Within this cohort, we assessed 21 patients who received systemic therapy. Survival was assessed in the overall cohort and in subgroups divided by clinicopathologic characteristics, including the extent of sarcomatoid features, Memorial Sloan-Kettering Cancer Center (MSKCC) risk criteria, Heng criteria, and the nature of systemic therapy rendered.ResultsOf the 21 patients assessed, 2 patients received chemotherapy, 7 patients received immunotherapy, and 12 patients received targeted agents as their first line treatment. Median overall survival (OS) in the overall cohort was 18.0 months (95% CI 6.9–22.0). By MSKCC criteria, patients with poor-risk disease had a median OS of 4.7 months, compared with 20.1 months for patients with intermediate-risk disease [hazard ratio (HR) 0.02, 95%CI 0.003–0.15; P = 0.0001]. A similar difference in median OS was seen poor- and intermediate-risk groups when stratifying by Heng criteria (HR 0.17, 95%CI 0.001–0.12). There was no significant difference in survival in patients with sarcomatoid predominant disease vs. nonpredominant disease (HR 0.62, 95%CI 0.23–1.65; P = 0.34), nor was there a difference amongst patients who received targeted therapies vs. nontargeted therapies (HR 1.0, 95%CI 0.61–1.40; P = 0.36).ConclusionsCompared with previous series and prospective trials assessing patients with sarcomatoid mRCC, the observed survival was prolonged. Although both Heng and MSKCC risk scores may be useful in determining prognosis, further studies are needed to identify relevant biomarkers and define the optimal therapeutic strategy for this disease.     

Obstructive sleep apnea and heart rate asymmetry microstructure during sleep

Purpose

Heart rate decelerations and accelerations have unequal input to heart rate variability (HRV) and patterns created by consecutive cardiac cycles—this phenomenon is known as heart rate asymmetry (HRA). The analysis of monotonic runs of heart rate decelerations and accelerations provides a detailed insight into the HRA microstructure and thus of HRV.

Aim

To evaluate the relation between the severity of obstructive sleep apnea (OSA) and the HRA microstructure during sleep.

Methods

Seventy-eight patients with suspected OSA underwent overnight polysomnography. The 300-min ECGs from the polysomnography were selected and analyzed. The HRA microstructure was quantified by measuring (1) the contribution of monotonic runs of decelerations or accelerations of different lengths to the number of all sinus beats, and (2) the length of the longest deceleration and acceleration runs.

Results

There were 19 patients with no/mild OSA (Apnea/Hypopnea Index (AHI) 5.1 ± 2.5/h), 18 with moderate OSA (AHI 21.8 ± 4.0/h) and 41 with severe OSA (AHI 42.8 ± 17.4/h). Patients with severe OSA had significantly reduced deceleration and acceleration runs of length 1 compared to the moderate OSA group, and compared to patients with no/mild OSA they had an increased number of longer runs (from 5 to 10 for accelerations and from 5 to 8 for decelerations; p < 0.05 for all comparisons). The longest acceleration runs were significantly longer in severe OSA group (p < 0.05) than in subjects with no/mild OSA.

Conclusions

HRA microstructure is related with OSA severity. An increased number of longer deceleration and acceleration runs is more common in severe OSA patients.