Clinical efficacy of once-daily micronized purified flavonoid fraction 1000 mg tablet in patients with symptomatic chronic venous disease

Aim: To investigate the clinical efficacy of micronized purified flavonoid fraction (MPFF) 1000?mg given as a single 1000?mg tablet once daily in patients suffering from chronic venous disease (CVD) vs MPFF 500?mg twice daily.

Methods: In an international, randomized, double-blind, parallel-group study, patients classified C0s to C4 according to Clinical Etiological Anatomic Pathophysiologic [CEAP] classification and with leg pain graded as superior to 4?cm on a 10-cm visual analog scale (VAS), were treated for 8 weeks with either MPFF 1000?mg once daily or MPFF 500?mg twice daily. The present post-hoc analysis focuses on the effect of treatment over time in patients randomized to the MPFF 1000?mg group. Leg pain was assessed at each follow-up visit by VAS. VAS scores over time were compared between each visit using paired Student t-tests.

Results: In total, 87 patients out of 174 were randomized to the MPFF 1000?mg group. Mean age?±?SD was 49.1?±?12.2 years, most of the patients were female (81.6%), the main CEAP classes of the most affected leg were C1 (20.7%), C2 (39.1%), C3 (33.33%), and the mean duration of CVD was 14.6?±?10.9 years. Patients with previous CVD treatment represent 27.6% of the patients. A MPFF 1000?mg tablet once daily was associated with a significant and continuous reduction in leg pain throughout the treatment period: –1.54?cm (±1.45) from baseline to week 2 (p?<?.01), –1.11?cm (±1.06) from week 2 to week 4 (p?<?.01), –1.57?cm (±1.05) from week 4 to week 8 (p?<?.01).

Conclusions: The new MPFF 1000?mg dose regimen in once daily tablets was associated with a rapid and continuous reduction in leg pain throughout the 8-week treatment period.     

Characterisation of peppermint (Mentha piperita L.) essential oil encapsulates

Aim: The aim was to choose the optimal encapsulation system and to incorporate encapsulates loaded with essential oil into the ice cream as a model food product.

Methods: Ca-alginate beads were produced by electrostatic extrusion process. Gelatine/alginate coacervates were processed with coacervation. Carnauba wax microparticles were produced using melt dispersion process. Morphological properties, chemical, and thermal stabilities of encapsulates were tested by SEM, FTIR spectral, and thermogravimetric analysis.

Results: Alginate provided sufficient emulsion stability over 1?h. Ca-alginate showed higher encapsulation efficiency (EE) (98.4?±?4.3%) compared to carnauba wax (94.2?±?7.8%) and gelatine/alginate coacervates (13.2?±?1.2%). The presence of essential oil in all three types of encapsulates confirmed with FTIR. The encapsulation process ensured controlled release and thermal stability of the oil.

Conclusions: Ca-alginate matrix as the most suitable for peppermint essential oil encapsulation. The sensory analysis showed that ice cream incorporating encapsulates is a promising system for the consumption of health beneficial peppermint essential oil.     

Velocity vector imaging for the assessment of segmental ventricular function in children with a single right ventricle after cavopulmonary anastomosis

Objective: Ventricular function assessment is very important for the treatment and prognostic classification of children with a single right ventricle (SRV) after cavopulmonary anastomosis (CPA). However, unusual ventricular shapes can result in inaccurate measurements. The aim of this study was to evaluate velocity vector imaging (VVI) for assessing segmental ventricular function in children with SRV after CPA.

Methods: Twenty-one children with SRV after CPA and 21 age- and sex-matched children with normal biventricular anatomy and function were included. The longitudinal velocity, displacement, strain and strain rate were measured in the two groups in six segments by VVI. The velocity, displacement, strain and strain rate of the SRVs were compared with max(dp/dt) measured during simultaneous cardiac catheterization in the SRV subjects.

Results: The control group consisted of 13 males and 8 females (69% males) with a mean age of 6.7?±?3.5 years and mean weight of 20.5?±?6.5?kg, and the study group consisted of 13 males and 8 females with a mean age 6.7?±?3.7 years and mean weight of 20.6?±?6.8?kg. Age, weight and sex distribution were similar between the groups (all, p?>?.05). Strain and strain rate values in all six segments were significantly lower in the study group than in the control group (all, p?<?.05). The max(dp/dt) of the SRV was 522.84?±?158.32?mmHg/s, and the strain rate of the basal segment at the rudimentary chamber correlated best with max(dp/dt) (r?=?0.74, p?<?.01).

Conclusions: Segmental ventricular dysfunction was present in children with SRV after CPA, and it could be assessed using VVI.     

Greater occipital and supraorbital nerve blockade for the preventive treatment of migraine: a single-blind,randomized, placebo-controlled study

Objective: Nerve injections have been used for the acute and preventive treatment of migraine in recent decades. Most of these injections focused on greater occipital nerve (GON) blockade. However, few studies were placebo controlled, and only a few of them investigated GON and supraorbital nerve (SON) blockade together. This study aimed to evaluate the efficacy of GON and SON blockade with local anesthetics for the preventive treatment of migraine without aura.

Methods: Eighty-seven patients diagnosed with migraine without aura were included in the study. Patients were divided randomly. One group was injected with 1% lidocaine, the other group was injected with 0.9% saline. GON and SON injections were done bilaterally. The injections were repeated weekly for 3 weeks. Patients were followed up for 2 months to assess clinical response.

Results: Seventy-one patients completed the study. After 2 months, the number of headache days decreased significantly from 12.8?±?10.9 to 5.3?±?7.4, and VAS decreased from 8.3?±?1.0 to 5.5?±?1.9 in the blockade group. The number of headache days decreased from 12.4?±?10.3 to 7.5?±?7.2 and VAS decreased from 8.2?±?1.1 to 7.4?±?1.3 in the placebo group. Response was seen in 65.1% of the patients in the blockade group (65.4% for episodic migraine, 64.7% for chronic migraine) and 28.6% of the patients in the placebo group. The difference was significant.

Conclusions: The results suggest that GON and SON blockade with lidocaine was more effective than the placebo in the prophylactic treatment of both episodic and chronic migraine.     

Usability and safety of SB5 (an adalimumab biosimilar) prefilled syringe and autoinjector in patients with rheumatoid arthritis

Objective: To demonstrate comparability between administration of the adalimumab biosimilar, SB5, via prefilled syringe (PFS) and autoinjector (AI) pen based on injection site pain, patient preference, and safety in rheumatoid arthritis (RA) patients.

Methods: In this phase 2, open-label study (NCT02565810; EudraCT Number 2014-004887-39), adult RA patients self-administered 40?mg SB5 subcutaneously via PFS at weeks 0 and 2, followed by AI at weeks 4, 6, 8, and 10. Patients rated injection site pain from 0 (no pain) to 10 (severe pain) using a visual numeric scale immediately and 15–30?min post-injection at weeks 0, 2, 4, and 6. Equivalence between PFS and AI was concluded if the 97.5% confidence interval (CI) of the difference in the injection site pain scores at weeks 2 and 6 was contained within the equivalence margin of ±5. Overall impression and preference for PFS and AI were also evaluated. Safety was assessed up to 20?weeks after the first injection.

Results: Of 49 patients enrolled, 48 completed the study. Mean injection site pain scores were equivalent between PFS and AI immediately (2.3 vs 2.0; 97.5% CI = ?0.99–0.30) and 15–30?min post-injection (0.8 vs 0.7; 97.5% CI = ?0.47–0.25). The overall impression of both devices was comparable. The overall preference of AI was higher than PFS. Treatment-emergent adverse events (TEAE) were mild-to-moderate. There were no severe or serious TEAEs reported during the study.

Conclusions: In RA patients, SB5 showed equivalent injection site pain and comparable safety when administered via PFS and AI.     

QAPSA: post-marketing surveillance of capsaicin 8% patch for long-term use in patients with peripheral neuropathic pain in France

Objective: To describe the characteristics of patients treated with the capsaicin 8% patch, prescribing conditions, long-term effects of repeat treatment on pain intensity and perception, quality of life, and impact on concomitant medication.

Methods: A national, longitudinal, prospective, non-interventional, post-marketing open study was conducted in 50 French pain centers. Adult volunteer non-diabetic patients with peripheral neuropathic pain receiving capsaicin 8% patch treatment were consecutively enrolled. Treatment could be repeated over a 12-month period, with 6?months’ follow-up after last application.

Results: A total of 684 patients (age: 53.0?±?14.9?years, mean?±?standard deviation; post-traumatic/surgical peripheral neuropathic pain: 76.3%; pain intensity: 6.2?±?1.7; pain duration: 3.0?years, median) were treated with 1 to 5 patches at 3/4?month intervals; 70.3% were naive to capsaicin 8% patch treatment at inclusion. Six months after last application, treatment was considered as successful for 21.8% (95% confidence interval: 17.5%–26.7%) of patients by a stringent criterion combining improvement according to the patient’s global impression of change (PGIC) and at least 30% improvement on a numerical pain rating scale (NPRS). Clinically relevant improvement in health-related quality of life was observed at end-of-study. No unexpected safety concerns were observed with capsaicin 8% patch repeat treatment.

Conclusions: The data of this post-marketing study meets the request by the French authorities for additional data on conditions of use in everyday practice. They confirmed the tolerance and long-term effect of capsaicin 8% patch in patients with peripheral neuropathic pain in real-world conditions.     

Is the endovascular embolization of tributaries of the internal iliac veins essential in the treatment of isolated pelvic-perineal reflux?

Aim: The aim of study was to investigate the opportunities of local phlebectomy in the elimination of isolated pelvic-perineal reflux (PPR), as well as to determine the feasibility of endovascular embolization of the tributaries of internal iliac veins in PPR. Clinical trial no. NCT01598051.

Materials and methods: The work is based on the results of examination and treatment of 43 female patients with varicose veins of the pelvis, perineum, and lower extremities. Patients had no signs of pelvic congestion syndrome (PCS). All patients underwent duplex ultrasound scanning (DUS) and ovariography with pelvic phlebography (OPP). For the elimination of PPR, local phlebectomy was performed in the major labia and perineal area, with maximal possible mobilization of the vessel within the operative wound (33 patients). In 10 patients with isolated varicose transformation of the superficial veins on the posterior thigh, mini-phlebectomy was performed using the Varady phlebectomy extractors.

Results and discussion: The varicose syndrome of the external genitalia, perineum, and posterior thigh was successfully treated in 100% of patients. Findings suggest that thorough mobilization and excision of the veins of the pudendal labia, perineum, and subcutaneous veins of the thigh is a reliable method for eliminating the pathological reflux from the intrapelvic veins to the superficial veins of the perineum and lower extremities. No recurrences of vulvar, perineal varices or dilation of the veins of the lower extremities were observed in 100% of patients over the 3-year follow-up period.

Conclusion: Local phlebectomy is an effective technique for eliminating the isolated PPR in patients with varicose transformation of intrapelvic, vulvar, or perineal veins. Endovascular embolization of the tributaries of the internal iliac veins is not an essential component in the treatment of PPR. The present study has a limitation due to the absence of patients with PCS. The effectiveness of phlebectomy in the treatment of isolated PPR was studied.     

Atorvastatin potentiates the effect of selenomethionine on thyroid autoimmunity in euthyroid women with Hashimoto’s thyroiditis

Objective: In many studies, selenium supplementation decreased serum titers of thyroid antibodies. The aim of the study was to investigate whether statin therapy determines selenium action on thyroid autoimmunity.

Methods: This prospective case-control study enrolled 42 euthyroid women with Hashimoto’s thyroiditis and normal vitamin D status, 20 of whom had been treated with atorvastatin (40?mg daily) for at least 6 months. All patients received selenomethionine (200 µg daily) for 6 months. Plasma levels of lipids, serum titers of thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) antibodies, as well as serum levels of thyrotropin, free thyroid hormones, and 25-hydroxyvitamin D were determined at the beginning and at the end of the study.

Results: At baseline, there were no differences between both treatment arms in plasma lipids, titers of thyroid antibodies, serum levels of thyrotropin, free thyroid hormones, and 25-hydroxyvitamin D. Selenometionine decreased titers of TPOAb (from 843?±?228 to 562?±?189?U/mL) and TgAb (from 795?±?286 to 501?±?216?U/mL) in atorvastatin-treated women, as well as titers of TPOAb (from 892?±?247 to 705?±?205?U/mL) and TgAb (from 810?±?301 to 645?±?224?U/mL) in statin-naive women. The changes in antibody titers were more pronounced in women receiving atorvastatin (between-group difference: 94 [32–156] [TPOAb]; 129 [52–206] [TgAb]). Treatment-induced changes in TPOAb and TgAb correlated positively with baseline thyroid antibody titers. Circulating levels of lipids, free thyroxine, free triiodothyronine, and 25-hydroxyvitamin D remained at similar levels throughout the study.

Conclusions: The obtained results indicate that the decrease in titers of thyroid antibodies was potentiated by atorvastatin use.     

Optimisation of the microencapsulation of lavender oil by spray drying

Background: Lavender oil consists of around 100 components and is susceptible to volatilisation and degradation reactions.

Aim: Microencapsulate lavender oil by spray drying using a biocompatible polymeric blend of gum acacia and maltodextrin to protect the oil components. Effect of total polymer content, oil loading, gum acacia, and maltodextrin proportions on the size, yield, loading, and encapsulation efficiency of the microparticles was investigated.

Methods: Morphology and oil localisation within microparticles were assessed by confocal laser scanning electron microscope. Structural preservation and compatibility were assessed using Fourier transform infra-red spectroscopy, differential scanning calorimetry, and gas chromatography–mass spectrometry.

Results: Lavender microparticles of size 12.42?±?1.79?µm prepared at 30 w/w% polymer concentration, 16.67 w/w% oil loading, and 25w/w% gum acacia showed maximum oil protection at high loading (12?mg w/w%), and encapsulation efficiency (77.89 w/w%).

Conclusion: Lavender oil was successfully microencapsulated into stable microparticles by spray drying using gum acacia/maltodextrin polymeric blend.     

In vivo study of mPEG–PCL as a nanocarriers for anti-inflammatory drug delivery of simvastatin

Purpose: In this study, methoxy poly (ethylene glycol)-poly (ε-caprolactone) (mPEG–PCL) di-block copolymers were synthesized. The purpose of this work is to investigate the in vivo anti-inflammatory effects of simvastatin-loaded micelles.

Methods: The structure of synthesized copolymers was characterized by using HNMR, FTIR, and GPC techniques. Simvastatin was encapsulated in micelles through a single-step nano-precipitation method, leading to the formation of simvastatin-loaded mPEG–PCL (simvastatin-mPEG–PCL) micelles. In this study, the anti-inflammatory effects of simvastatin/mPEG–PCL micelles versus indomethacin were investigated in acute inflammation-induced rats. The paw edema thickness was measured 1, 2, 3, and 4?h after injection of formulation. The inhibition of edema in various groups were calculated and reported by percentages.

Results: The results showed that the zeta potential of micelles was about ?14.9?±?0.47?mV and the average size was in range of 66.10?±?0.34?nm. Simvastatin was encapsulated in mPEG–PCL micelles with a loading capacity of 9.63?±?0.87% and an encapsulation efficiency of 64.20?±?0.79%. Simvastatin and simvastatin-mPEG–PCL micelles showed significant anti-inflammatory activity in the present study.

Conclusions: This study revealed that simvastatin and simvastatin/mPEG–PCL micelles both have anti-inflammatory effects and suggested that statins have potential anti-inflammatory activity along with their lipid lowering properties.     

Comparison of a twice daily injection of insulin aspart 50 with insulin aspart 30 in patients with poorly controlled type 2 diabetes

Objective: To compare the efficacy and safety of a twice daily injection of insulin aspart (BIAsp) 30 and BIAsp50 in patients with type 2 diabetes mellitus (T2DM) poorly controlled with oral hypoglycemic agents (OHAs).

Methods: In this 12 week prospective, randomized, parallel trial, a total of 80 T2DM patients, 59?±?10?years old with a disease duration of 9.3?±?6.6?years and HbA1c >7% despite large doses of metformin and sulfonylurea administration, were randomized to receive BIAsp30 (n?=?40) or BIAsp50 (n?=?40). The primary endpoint was a change in HbA1c at week 12.

Results: The changes in HbA1c from baseline were ?2.5%?±?1.0% in the BIAsp50 group and ?2.5%?±?1.2% in the BIAsp30 group (p?=?.897). No difference was observed in the rate of HbA1c target achievement (<7.0%) between BIAsp50 (42.5%) and BIAsp30 (32.5%) (p?=?.495). The change in fasting plasma glucose (FPG) in the BIAsp50 group was lower than that in the BIAsp30 group (p?<?.001), while the change in two-hour postprandial blood glucose (2hPBG) was higher and blood glucose excursion was lower in the BIAsp50 group than that in the BIAsp30 group (p?<?.001, p?<?.001). A significant improvement in HbA1c was observed with BIAsp50 in subgroups with baseline blood glucose excursion >7.8?mmol/L or 2hPBG >17.6?mmol/L compared with BIAsp30. There were no differences in hypoglycemia or body weight between groups.

Conclusions: Compared with BIAsp30, BIAsp50 showed greater efficacy in patients with baseline BG excursion >7.8?mmol/L or 2hPBG >17.6?mmol/L as well as good safety for hypoglycemia.

Clinical trial registration: ChiCTR-IIR-16008958.     

Interaction of deoxyschizandrin and schizandrin B with liver uptake transporters OATP1B1 and OATP1B3

1. Deoxyschizandrin and schizandrin B have diverse pharmacological effects, including hepatoprotective activity. We aim to study their hepatic uptake and their effects on the hepatic uptake of other clinical drugs mediated by OATP1B1 and OATP1B3.

2. Deoxyschizandrin exhibited a high affinity for OATP1B1 with K_m of 17.61?±?0.43?μM but a low affinity for OATP1B3. Similarly, schizandrin B also showed a strong affinity for OATP1B1 with K_m of 18.45?±?1.23?μM but a weak affinity for OATP1B3.

3. Atorvastatin and rifampicin could inhibit the uptake of deoxyschizandrin and schizandrin B mediated by OATP1B1.

4. Intriguingly, both deoxyschizandrin and schizandrin B significantly promoted the uptake of atorvastatin (with EC₅₀ of 50.58?±?8.08 and 24.70?±?5.82 µM, respectively) and rosuvastatin (with EC₅₀ of 13.46?±?2.70 and 8.99?±?4.73 µM, respectively) mediated by OATP1B1. Deoxyschizandrin could markedly promote the uptake of fluvastatin but inhibit the uptake of sodium taurocholate (TCNa) mediated by OATP1B1.

5. The promotion on hepatic uptake of statins mediated by OATP1B1 might lead to enhanced efficacy of cholesterol lowering and reduced risk of myopathy for hyperlipidemia patients when given statins together with deoxyschizandrin or schizandrin B.     

The impact of adaptive iterative dose reduction 3D on the improvement of shoulder image quality in head and neck CTA

Objective: The aim of this study was to determine the impact of adaptive iterative dose reduction 3?D (AIDR3D) on the improvement of shoulder image quality in low-radiographic dose head and neck CT angiography (CTA).

Materials and methods: Ninety patients who underwent CTA examination were randomly divided into two groups, namely group A (n?=?45) and B (n?=?45). Patients in group A were scanned under 120?kV and 300?mA, with images reconstructed by filtered back projection (FBP), and patients in group B were scanned under 80?kV and auto mA with images reconstructed by AIDR3D. Image quality was accessed by two experienced radiologists. The noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of common carotid artery (CCA) at C7 level, and radiation dosage were compared between the two groups.

Results: The score of CCA in group B was significantly higher than group A (p?<?0.05), and there were no significant differences in the scores of carotid sinus and internal carotid artery between the two groups (p?>?0.05). The score of intracranial artery in group B was lower than that of group A, however, the image quality in group B can meet the requirement of clinical diagnosis. The noise value of CCA at C7 level in group B was significantly lower than that of group A (p?<?0.05). SNR and CNR values of CCA at C7 level in group B were significantly higher than those of group A (p?<?0.05). Effective radiation dose in group B was significantly decreased compared with group A (p?<?0.05).

Conclusion: AIDR3D remarkably improved image quality in low-radiographic dose head and neck CTA over FBP, which made the low-dose CTA images meet the requirement of clinical diagnosis.     

A randomized,double-blinded,placebo-controlled,parallel trial of vitamin D3 supplementation in adult patients with migraine

Background: Vitamin D levels have been linked to certain pain states, including migraine. This study investigated whether vitamin D supplementation would be beneficial for adult patients with migraine (ClinicalTrials.gov Identifier: NCT01695460).

Methods: A randomized, double-blinded, placebo-controlled parallel trial was conducted in migraine patients (36 women and 12 men, 18–65 years of age). A 4-week baseline period was conducted before randomization to 24 weeks of treatment. Participants were assigned to receive D3-Vitamin (n?=?24, 18 women and 6 men, 100?μg/day D3-Vitamin) or placebo (n?=?24,?18 women and 6 men). Migraine attacks and related symptoms were assessed by self-reported diaries. The response rate (i.e. experiencing a 50% or greater reduction in migraine frequency from baseline to week 24), change in migraine severity, and number of migraine days were recorded. Changes in migraine-related symptoms, HIT-6^TM scores, and pain sensitivity tests (pressure pain threshold and temporal summation) were also evaluated. Serum levels of both 25 (OH)D and 1,25 (OH)₂D were assessed from baseline to week 24.

Results: The number of headache days changed from 6.14?±?3.60 in the treatment group and 5.72?±?4.52 in the placebo group at baseline to 3.28?±?3.24 and 4.93?±?3.24 by the end of the trial, respectively. Migraine patients on D3-Vitamin demonstrated a significant decrease (p?<?.001) in migraine frequency from baseline to week 24 compared with placebo. However, migraine severity, pressure pain thresholds, or temporal summation did not show a significant change. 25(OH)D levels increased significantly for the D3-Vitamin group during the first 12 weeks of treatment. There was no significant change in 1,25(OH)₂D. No side-effects were reported or noted.

Conclusions: D3-Vitamin was superior to placebo in reducing migraine days in migraine patients. Larger studies are required to confirm that vitamin D₃ might be one of the prophylactic options for adult patients with migraine.     

High one-year mortality following hospitalization for severe hypoglycemia among patients with diabetes mellitus: findings of a retrospective cohort study at an acute tertiary care hospital in Singapore

Objectives: Little is known about the 1-year short-term mortality rate following hospital admissions with severe hypoglycemia. This study aimed to determine the factors associated with increased 1-year mortality rate following hospitalization in diabetes patients admitted with severe hypoglycemia to the Singapore General Hospital.

Methods: Clinical, biochemical, and 1-year mortality data from diabetes patients who were admitted with severe hypoglycemia in the year 2014 were extracted from institutional medical records. Patients who passed away during the episode of admissions with severe hypoglycemia were excluded from the analysis. The clinical and biochemical factors between patients who survived and those who did not survive within 1 year following admission were compared using logistic regression analysis.

Results: Three hundred and four patients (181 female and 123 male) were admitted with severe hypoglycemia in 2014, and the mean capillary blood glucose on admission was 2.3?±?0.7?mmol/L. Sixty-three (20.7%) patients died within 1-year post-discharge from the hospital. Compared with patients who survived 1-year post-discharge from the hospital, non-survivors were older (69.3?±?11.0 vs 75.5?±?11.2 years, p?<?.001), had longer lengths of stay (LOS) (5.0?±?7.4 vs 9.0?±?12.8 days, p?=?.02), and had a higher Charlson Comorbidity Index (CCI) (4.1?±?1.9 vs 5.9?±?2.4, p?<?.001). Factors associated with increased 1-year mortality risk were age (odds ratio [OR]?=?1.06; 95% confidence interval [CI]?=?1.03–1.09, p?<?.01), LOS in hospital (OR?=?1.01; 95% CI?=?1.01–1.08, p?<?.01), and CCI (OR?=?1.51; 95% CI?=?1.31–1.75, p?<?.01), respectively.

Conclusions: Older diabetes patients with more comorbidities and longer LOS were at increased risk of dying within a year of discharge after hospitalization with severe hypoglycemia. Admission with severe hypoglycemia has important prognostic implications. Healthcare professionals should address hypoglycemia and other health issues during the hospital admissions.     

Insulin-like growth factor-1 (IGF-1) poly (lactic-co-glycolic acid) (PLGA) microparticles – development,characterisation, and in vitro assessment of bioactivity for cardiac applications

Aim: The aim of this study was to evaluate the formulation of a synthetic IGF-1 (pIGF-1) in PLGA microparticles (MP).

Methods: Poly (lactic-co-glycolic acid) (PLGA) MPs loaded with pIGF-1 were prepared, characterised and evaluated using double emulsion solvent evaporation method.

Results: Spherical MPs showed an average particle size of 2?µm, encapsulation efficiency (EE) of 67% and 50% degradation over 15?days. With a view to enhancing retention in the myocardium, the MP formulation was encapsulated in a cross-linked hyaluronic acid hydrogel. pIGF-1 released from MPs and from MPs suspended in hyaluronic acid hydrogel remained bioactive, determined by a significant increase in cellular proliferation of c-kit⁺ cells.

Conclusion: This formulation has potential for loco-regional delivery to damaged myocardium to promote the survival of cardiomyocytes.     

Effects of quercetin on the pharmacokinetics of losartan and its metabolite EXP3174 in rats

1. This study investigates the influence of quercetin on the pharmacokinetics of losartan and its metabolite EXP3174 in rats.

2. The pharmacokinetic profiles of losartan and EXP3174 of orally administered losartan (10?mg/kg) with or without pretreatment with quercetin (20?mg/kg/day for 7 days) were investigated. Additionally, Caco-2 cell transwell model and rat liver microsome incubation experiments were also conducted to investigate its potential mechanism.

3. The results showed that when the rats were pretreated with quercetin, the C_max (2.16?±?0.40 vs. 1.33?±?0.21?mg/L) and the AUC_(0–t) (13.89?±?1.22 vs. 7.34?±?0.75?mg·h/L) of losartan increased significantly (p?<?.05), and while the C_max (0.76?±?0.09 vs. 1.14?±?0.18?mg/L) of EXP3174 decreased significantly compared to the control (p?<?.05). The t_1/2 of losartan was prolonged from 3.27?±?0.45?h to 4.74?±?0.51?h (p?<?.05). The results also indicated that quercetin could increase losartan absorption rate by inhibiting the activity of P-gp and decrease its metabolic stability by inhibiting the activity of CYP450 enzyme.

4. These results indicated that the herb–drug interaction between quercetin and losartan might occur when they are co-administered in rats, quercetin could increase the systemic exposure of losartan and decrease the plasma concentration of EXP3174, possibly by inhibiting the activity of P-gp or CYP450 enzyme.     

Stress-related upper gastrointestinal bleeding in adult neurocritical care patients: a Chinese multicenter,retrospective study

Objective: China has limited data on stress-related gastrointestinal ulcers in patients admitted for neurosurgical care. This study evaluated the incidence of upper gastrointestinal bleeding (UGIB) and use of stress ulcer prophylaxis (SUP) in Chinese neurocritical care patients (Glasgow Coma Scale [GCS] score ≤10).

Methods: This multicenter, retrospective study was performed from January 2015 to July 2015. Medical records of 1468 patients hospitalized during 2014 were reviewed. An estimated UGIB incidence rate of 4.4% was considered for precision of 1.3% for estimation of UGIB. The primary endpoint was evaluation of overall incidence of any overt UGIB in ≤14 days after cerebral lesion. Secondary endpoints included incidence of UGIB with or and without clinically significant complications, time to UGIB, associated risk factors and SUP used.

Results: We analyzed 1416 patients (mean age: 53.7?±?14.00 years; males: 62.4%) with cerebral lesions. Overall incidence rate of UGIB ≤14 days was 12.9% (95% CI: 11.2%–14.7%), 0.76% with and 12.1% without significant clinical complications. Average time and duration of bleeding were 2.9?±?3.37 days and 4.2?±?8.4 days, respectively. The most significant risk factors for UGIB were mechanical ventilation for >48?hours (p?<?.0001), UGIB history (p?=?.0026) and use of anticoagulants (p?<?.0001). Acid-suppression drugs were administered for SUP in 79.0% of the patients, whereas 40.5% received hemostatic drugs.

Conclusions: The rate of UGIB incidence was higher than the estimated rate in neurocritical care patients in China, suggesting the need for better management and treatment for stress-related mucosal disease in China. History of UGIB, mechanical ventilation and/or anticoagulants significantly affected UGIB.

ClinicalTrials registry number: NCT02316990.     

Bone-targeted agent treatment patterns and the impact of bone metastases on patients with advanced breast cancer in the United States

Objective: Bone metastases are common among patients with advanced breast cancer, putting patients at increased risk of skeletal-related events (SREs). This study described impact of bone metastases, utilization of bone-targeted agents (BTAs) and physicians’ decision processes for BTA use in advanced breast cancer.

Methods: Data were collected using the Adelphi Breast Cancer Disease-Specific Programme in the United States. Physicians completed a detailed record for eligible patients (women ≥18?years, with stage IIIB–IV breast cancer).

Results: Data available from 1276 patients with advanced breast cancer included 485 (38%) with bone metastases. Most (80%) reported pain at bone metastasis diagnosis; of those reporting pain, 55% reported moderate to severe pain. Among patients with bone metastasis, 69% received a BTA. Reasons for initiating BTAs were bone pain (32%) and an estimated high risk of SREs (25%). Reasons for not treating with BTAs were very recent diagnosis (37%), poor Karnofsky performance status (14%), perceived low risk of SREs (11%) and short life expectancy (11%). Zoledronic acid (48%) and denosumab (42%) were commonly used BTAs; the main reasons for initiating BTA treatment were long-term safety (28% and 32%, respectively) and efficacy in delaying SREs (15% and 31%, respectively). The analysis was not adjusted for age or other possible confounders.

Conclusion: Bone pain is a common and sometimes severe symptom of bone metastases in advanced breast cancer and a common reason for initiating BTA treatment. Safety and efficacy were the main factors considered by physicians when selecting BTAs.