Real-world Evidence for the Antianginal Efficacy of Trimetazidine from the Russian Observational CHOICE-2 Study

Introduction

The guidelines recommend a beta-blocker or calcium channel blocker as the first-line medication for angina, supplemented by other agents for additional symptoms. One such agent is trimetazidine (TMZ), which has been shown to reduce the frequency of anginal episodes and improve exercise performance without affecting haemodynamic parameters. However, extensive real-world evidence for its efficacy in combination with first-line therapies has been lacking.

Methods

The aim of this large-scale, Russian, multicentre, 6-month, open-label, prospective observational study was to assess the effect of adding TMZ modified release 35 mg bid to background antianginal therapy in the real-world clinical setting.

Results

The study included 896 patients: 54% women, aged 29–90 years (42.6% >65 years), 63% with class II angina, and receiving beta-blockers alone or in combination (93%). Add-on TMZ reduced angina frequency and short-acting nitrate use within 2 weeks (both p < 0.0001) regardless of background therapy and maintained this effect over 6 months. It increased the proportion of patients with class I angina sixfold while decreasing that of class 3 angina almost fourfold. It also improved walking distance and well-being at 6 months (both p < 0.0001). Treatment was well tolerated.

Conclusion

Add-on TMZ is a safe and rapidly effective treatment for reducing angina attacks and nitrate use in the real-world clinical setting. It also increases exercise capacity and well-being. These effects are observed within 2 weeks and persist for at least 6 months.

     

Anti-Anginal Effectiveness and Tolerability of Trimetazidine Modified Release 80 Mg Once Daily in Stable Angina Patients in Real-World Practice

Introduction

Trimetazidine (TMZ) was shown to reduce angina symptoms and increase the exercise capacity in stable angina (SA) patients. A new formulation allowing a once-daily (od) dosage could improve patients’ satisfaction and adherence.

Methods

ODA was a 3-month, observational, multicenter, prospective Russian study in SA patients with persistent symptoms despite therapy. Angina attack frequency, short-acting nitrate (SAN) consumption, adherence to antianginal medications, and overall efficacy and tolerability of TMZ 80 mg od were assessed in a real-world setting.

Results

A total of 3066 patients were included (mean age 62.8, 48% male). After 3 months, TMZ 80 mg od treatment led to a significant (p?<?0.001) decrease in angina attack frequency (from 4.7?±?3.5 to 0.9?±?1.3/week) and SAN use (from 4.5?±?3.9 to 0.7?±?1.3/week). Overall tolerability and effectiveness were rated as “very good” by the majority of physicians. Medication adherence improved significantly, with good adherence reported by 56% of patients (vs. 24% at baseline, p?<?0.0001) and non-adherence by 3% (vs. 36% at baseline, p?<?0.0001) at month 3. Patient satisfaction with TMZ od was 9.5 [on a scale of 1 to 10 (very satisfied)]. Patients reported improved physical activity: more patients reported no limitations (15% vs. 1% at baseline p?<?0.01), slight limitation (46% vs. 5% at baseline, p?<?0.001) or moderate limitation (30% vs. 23%, p?<?0.01) and fewer patients reported substantial limitation (8% vs. 52% at baseline, p?<?0.001) or very marked reduction (1% vs. 19% at baseline, p?<?0.01) at month 3.

Conclusion

In this prospective, observational study, TMZ 80 mg od effectively reduced angina attacks and SAN consumption, improved physical activity and adherence and was well tolerated in chronic SA patients.

Trial Registration

ISRCTN registry Identifier, ISRCTN97780949.

Funding

Servier.

Plain Language Summary

Plain language summary available for this article.

     

Efficacy of Ivabradine in Combination with Beta-Blockers Versus Uptitration of Beta-Blockers in Patients with Stable Angina (CONTROL-2 Study)

Introduction

Heart rate (HR) reduction is an integral part of antianginal therapy, but many patients do not reach the guideline-recommended target of less than 60 bpm despite high use of beta-blockers (BB). Failure to uptitrate BB doses may be partly to blame. To explore other options for lowering HR and improving angina control, CONTROL-2 was initiated to compare the efficacy and tolerability of the combination of BBs with ivabradine versus uptitration of BBs to maximal tolerated dose, in patients with stable angina.

Methods

This multicenter, open, randomized study included 1104 patients with Canadian Cardiovascular Society (CCS) class II or III stable angina, in sinus rhythm, and on background stable treatment with non-maximal recommended doses of BBs. Consecutive patients were allocated to ivabradine + BB or BB uptitration in a 4:1 ratio.

Results

At the end of the study (week 16), addition of ivabradine to BB treatment and BB uptitration resulted in reduction in HR (61 ± 6 vs. 63 ± 8 bpm; p = 0.001). At week 16, significantly more patients on ivabradine + BB were in CCS class I than with BB uptitration (37.1% vs. 28%; p = 0.017) and significantly more patients were angina-free (50.6% vs. 34.2%; p < 0.001). Patient health status based on the visual analogue scale (VAS) was also better in the ivabradine + BB group. Adverse events (AEs) were significantly more common with BB uptitration than with the ivabradine + BB combination (18.4% vs. 9.4%, p < 0.001).

Conclusion

In patients with stable angina, combination therapy with ivabradine + BB demonstrated good tolerability, safety, and more pronounced clinical improvement, compared to BB uptitration.

Trial Registration

ISRCTN30654443.

Funding

Servier.

     

Ivabradine in combination with beta-blocker improves symptoms and quality of life in patients with stable angina pectoris: results from the ADDITIONS study

Aim

Several clinical trials have demonstrated the antianginal and anti-ischemic efficacy of ivabradine in combination with beta-blocker in patients with stable angina pectoris. The ADDITIONS (PrActical Daily efficacy anD safety of Procoralan^® In combinaTION with betablockerS) study evaluated the efficacy, safety, and tolerability of ivabradine added to beta-blocker, and its effect on angina symptoms and quality of life in routine clinical practice.

Methods

This non-interventional, multicenter, prospective study included 2,330 patients with stable angina pectoris treated with a flexible dose of ivabradine twice daily in addition to beta-blocker for 4 months. The parameters recorded included heart rate, number of angina attacks, nitrate consumption, tolerance, and quality of life.

Results

After 4 months ivabradine (mean dose 12.37 ± 2.95 mg/day) reduced heart rate by 19.4 ± 11.4 to 65.6 ± 8.2 bpm (p < 0.0001). The number of angina attacks was reduced by 1.4 ± 1.9 per week (p < 0.0001), and nitrate consumption by 1.9 ± 2.9 U per week (p < 0.0001). At baseline (i.e., on beta-blocker), half of the patients (51%) were classified as Canadian Cardiovascular Society (CCS) grade II; 29% were CCS grade I. After 4 months’ treatment with ivabradine, most of the patients were CCS grade I (68%). The EQ-5D index improved by 0.17 ± 0.23 (p < 0.0001). The overall efficacy of ivabradine was considered by the physicians as “very good” (61%) or “good” (36%) in most patients. Suspected adverse drug reactions were documented in 14 patients; none were severe.

Conclusion

In daily clinical practice, combining ivabradine with beta-blocker not only reduces heart rate, number of angina attacks, and nitrate consumption, but also improves the quality of life in patients with stable angina pectoris.

     

Pooled Aquablation Results for American Men with Lower Urinary Tract Symptoms due to Benign Prostatic Hyperplasia in Large Prostates (60–150 cc)

Introduction

To present short-term safety and efficacy data of men with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) treated with Aquablation.

Methods

Men with LUTs secondary to BPH (60–150 cc) underwent Aquablation treatment from February 2016 to December 2017 across 17 investigational sites in the USA from two contemporary investigational device exemption (IDE) studies called WATER (NCT02505919) and WATER II (NCT03123250).

Results

One hundred seven males with mean age of 67.3?±?6.5 years were treated with Aquablation; mean prostate volume was 99.4?±?24.1 cc. The pooled results show that large prostates have an average procedure time of less than 36 min and discharge on average 1.6?±?1 days. The IPSS decreased by 16.7?±?8.1 points at 3 months and Q_max increased by 11.2?±?12.4 ml/s. The Clavien-Dindo (CD) grade 2 or higher event rate at 3 months was 29%. A non-hierarchical breakdown for CD events yielded 18% grade 2 and 19% grade 3 or higher.

Conclusion

Men with LUTS secondary to BPH (60–150 cc) in a pooled analysis were treated safely and effectively with Aquablation up to 3 months postoperatively.

Trial Registration

ClinicalTrials.gov identifiers, NCT02505919 and NCT03123250.

Funding

PROCEPT BioRobotics.

     

Automatic adjustment of pressure support by a computer-driven knowledge-based system during noninvasive ventilation: a feasibility study

Objective

To evaluate the feasibility of using a knowledge-based system designed to automatically titrate pressure support (PS) to maintain the patient in a “respiratory comfort zone” during noninvasive ventilation (NIV) in patients with acute respiratory failure.

Design and setting

Prospective crossover interventional study in an intensive care unit of a university hospital.

Patients

Twenty patients.

Interventions

After initial NIV setting and startup in conventional PS by the chest physiotherapist NIV was continued for 45?min with the automated PS activated.

Measurements and results

During automated PS minute-volume was maintained constant while respiratory rate decreased significantly from its pre-NIV value (20?±?3 vs. 25?±?3?bpm). There was a trend towards a progressive lowering of dyspnea. In hypercapnic patients PaCO₂ decreased significantly from 61?±?9 to 51?±?2?mmHg, and pH increased significantly from 7.31?±?0.05 to 7.35?±?0.03. Automated PS was well tolerated. Two system malfunctions occurred prompting physiotherapist intervention.

Conclusions

The results of this feasibility study suggest that the system can be used during NIV in patients with acute respiratory failure. Further studies should now determine whether it can improve patient-ventilator interaction and reduce caregiver workload.

     

Distribution of lung ventilation in spontaneously breathing neonates lying in different body positions

Objective

The aim of our study was to determine the effect of the irregular spontaneous breathing pattern and posture on the spatial distribution of ventilation in neonates free from respiratory disease by the non-invasive imaging method of electrical impedance tomography (EIT). Scanning of spontaneously breathing neonates is the prerequisite for later routine application of EIT in babies with lung pathology undergoing ventilator therapy.

Design

Prospective study.

Setting

Neonatal intensive care unit at a university hospital.

Patients

Twelve pre-term and term neonates (mean age: 23 days; mean body weight: 2,465 g; mean gestational age: 34 weeks; mean birth weight: 2,040 g).

Interventions

Change in body position in the sequence: supine, right lateral, prone, supine.

Measurements and results

EIT measurements were performed using the Göttingen GoeMF I system. EIT scans of regional lung ventilation showing the distribution of respired air in the chest cross-section were generated during phases of rapid tidal breathing and deep breaths. During tidal breathing, 54.5±8.3%, 55.2±10.5%, 59.9±8.4% and 54.2±8.5% of inspired air (mean values ± SD) were directed into the right lung in the supine, right lateral, prone and repeated supine postures respectively. During deep inspirations, the right lung ventilation accounted for 52.6±7.9%, 68.5±8.5%, 55.4±8.2% and 50.5±6.6% of total ventilation respectively.

Conclusion

The study identified the significant effect of breathing pattern and posture on the spatial distribution of lung ventilation in spontaneously breathing neonates. The results demonstrate that changes in regional ventilation can easily be determined by EIT and bode well for the future use of this method in paediatric intensive care.

     

Breakthrough Cancer Pain: Preliminary Data of The Italian Oncologic Pain Multisetting Multicentric Survey (IOPS-MS)

Introduction

An ongoing national multicenter survey [Italian Oncologic Pain multiSetting Multicentric Survey (IOPS-MS)] is evaluating the characteristics of breakthrough cancer pain (BTP) in different clinical settings. Preliminary data from the first 1500 cancer patients with BTP enrolled in this study are presented here.

Methods

Thirty-two clinical centers are involved in the survey. A diagnosis of BTP was performed by a standard algorithm. Epidemiological data, Karnofsky index, stage of disease, presence and sites of metastases, ongoing oncologic treatment, and characteristics of background pain and BTP and their treatments were recorded. Background pain and BTP intensity were measured. Patients were also questioned about BTP predictability, BTP onset (≤10 or >10 min), BTP duration, background and BTP medications and their doses, time to meaningful pain relief after BTP medication, and satisfaction with BTP medication. The occurrence of adverse reactions was also assessed, as well as mucosal toxicity.

Results

Background pain was well controlled with opioid treatment (numerical rating scale 3.0 ± 1.1). Patients reported 2.5 ± 1.6 BTP episodes/day with a mean intensity of 7.5 ± 1.4 and duration of 43 ± 40 min; 977 patients (65.1%) reported non-predictable BTP, and 1076 patients (71.7%) reported a rapid onset of BTP (≤10 min). Higher patient satisfaction was reported by patients treated with fast onset opioids.

Conclusions

These preliminary data underline that the standard algorithm used is a valid tool for a proper diagnosis of BTP in cancer patients. Moreover, rapid relief of pain is crucial for patients’ satisfaction. The final IOPS-MS data are necessary to understand relationships between BTP characteristics and other clinical variables in oncologic patients.

Funding

Molteni Farmaceutici, Italy.

     

Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer

Purpose

The aim of this work was to develop a CAIX-specific nanobody conjugated to IRDye800CW for molecular imaging of pre-invasive breast cancer.

Procedures

CAIX-specific nanobodies were selected using a modified phage display technology, conjugated site-specifically to IRDye800CW and evaluated in a xenograft breast cancer mouse model using ductal carcinoma in situ cells (DCIS).

Results

Specific anti-CAIX nanobodies were obtained. Administration of a CAIX-specific nanobody into mice with DCIS xenografts overexpressing CAIX showed after 2 h a mean tumor-to-normal tissue ratio (TNR) of 4.3?±?0.6, compared to a TNR of 1.4?±?0.2 in mice injected with the negative control nanobody R2-IR. In DCIS mice, a TNR of 1.8?±?0.1 was obtained. Biodistribution studies demonstrated an uptake of 14.0?±?1.1 %I.D./g in DCIS?+?CAIX tumors, 4.6?±?0.8 %I.D./g in DCIS tumors, while 2.0?±?0.2 %I.D./g was obtained with R2-IR.

Conclusions

These results demonstrate the successful generation of a CAIX-specific nanobody-IRDye800CW conjugate that can be used for rapid imaging of (pre-)invasive breast cancer.

     

Outcomes Following Implantation of Two Second-Generation Trabecular Micro-Bypass Stents in Patients with Open-Angle Glaucoma on One Medication: 18-Month Follow-Up

Introduction

The study objective was to evaluate the intraocular pressure (IOP) and medication-lowering effect of 2 second-generation trabecular micro-bypass stents in eyes with open-angle glaucoma (OAG) on one preoperative medication.

Methods

Fifty-seven qualified phakic eyes with OAG on 1 medication, preoperative medicated IOP of 18–30 mmHg, and preoperative unmedicated (post-washout) IOP of 22–38 mmHg underwent implantation of 2 second-generation trabecular micro-bypass stents in a standalone procedure. Evaluations included IOP, best-corrected visual acuity, medication use, fundus and slit lamp examinations, visual field, cup to disc ratio, pachymetry, and complications and interventions. Subjects have been followed for 18 months, and follow-up is ongoing.

Results

At Month 12 postoperative, 100% of eyes had achieved an IOP reduction ≥20% (100% had IOP ≤18 mmHg and 67% had IOP ≤15 mmHg) without medication versus preoperative unmedicated IOP, and 75% had IOP reduction ≥20% without medication versus preoperative medicated IOP. The Month 12 mean unmedicated IOP had decreased by 42%, to 14.2 ± 1.9 mmHg vs 24.4 ± 1.3 mmHg preoperatively, and this reduction was maintained through 18 months (14.4 ± 2.1 mmHg). A high safety profile was observed.

Conclusion

In this prospective, open-label, single-arm study, the standalone implantation of two second-generation trabecular micro-bypass stents in OAG patients on 1 preoperative medication resulted in IOP reduction to ≤15 mmHg and elimination of medication through 18 months, with favorable safety.

Trial Registration

ClinicalTrials.gov identifier, NCT02868190.

Funding

Glaukos Corporation, San Clemente, CA.

     

Intrapartum transperineal ultrasound for evaluating uterine contraction intensity in the second stage of labor

Purpose

To clarify whether intrapartum transperineal ultrasound (ITU) can be used to evaluate uterine contraction intensity, and whether the intensity is associated with the duration of the second stage.

Methods

A prospective observational study was performed involving 86 women with a normal singleton term fetus and more than three contractions every 10 min. ITU was performed for contractile and non-contractile periods of labor at the beginning of the second stage, and one representative “angle of progression (AoP)” image was selected for each period. The Mann–Whitney U test was used to compare ?AoP, the difference between the two angles, depending on the duration of the second stage. Receiver operating characteristic curves were used to evaluate the probability of duration of the second stage ≤50 min in nulliparous women.

Results

Among nulliparous women, ΔAoP differed significantly according to the duration of the second stage (52.5° ± 5.0° for ≤50 min vs. 30.9° ± 2.1° for >50 min; P < 0.001). Receiver operating characteristic curve analysis showed that approximately 85% of nulliparous women with ΔAoP greater than 40° delivered within 50 min.

Conclusion

These findings could be utilized in the evaluation of uterine contraction intensity, and ?AoP measurement could be used to predict the duration of the second stage of labor in nulliparous women.

     

Determination of functional residual capacity by oxygen washin-washout: a validation study

Objective

To validate a new system for functional residual capacity (FRC) measurements using oxygen washin/washout in spontaneously breathing humans. The system (LUFU, Drägerwerk AG, Lübeck, Germany) consists of an unmodified EVITA 4 ventilator, a side-stream paramagnetic oxygen sensor and a dedicated software.

Design

Laboratory study and measurements in spontaneously breathing volunteers.

Setting

Pulmonary function laboratory of a university hospital.

Participants

20 healthy and 15 lung diseased volunteers.

Interventions

FRC was measured by LUFU (LUFU-FRC) and by helium dilution (He-FRC); intra-thoracic gas volume (ITGV) was determined by body plethysmography. Each measurement cycle consisted of four independent LUFU-FRC determinations (step change of FiO₂ from 0.21 to 0.5 and back and from 0.21 to 1.0 and back), two helium-dilution runs and two body box measurements. Repeatability and agreement between methods were determined by comparing different measurements of one technique and by comparing different techniques among each other.

Measurements and results

Repeatability of LUFU-FRC was estimated by comparing washin to washout and the different FiO₂steps. The difference of the means was 3.7% at the most. Agreement between methods resulted in the following differences (mean?±?standard deviation of differences) for healthy and lung-diseased volunteers, respectively: LUFU-FRC vs. He-FRC –0.40?±?0.50?L (0.02?±?0.95?L), LUFU-FRC vs. ITGV –0.43?±?0.54?L (–0.18?±?0.61?L) and He-FRC vs. ITGV –0.03?±?0.43?L (–0.20?±?0.98?L).

Conclusions

LUFU is a non-invasive method for the determination of FRC that requires only minor additional equipment and no modification to the ventilator. It can be used in difficult conditions such as breathing patterns with variations from breath to breath. The results of this study show that LUFU is sufficiently reliable and repeatable to warrant its clinical application.

     

Efficiency of quantitative echogenicity for investigating supraspinatus tendinopathy by the gray-level histogram of two ultrasound devices

Purpose

The gray-level histogram of ultrasound is a promising tool for scanning the hypoechogenic appearance of supraspinatus tendinopathy, and the aim of this study was to test the hypothesis that the gray-level value of the supraspinatus tendon in the painful shoulder has a lower value on B-mode images even though in different ultrasound devices.

Methods

Sixty-seven patients who had unilateral shoulder pain with rotator cuff tendinopathy underwent bilateral shoulder ultrasonography, and we compared the mean gray-level values of painful shoulders and contralateral shoulders without any pain in each patient using two ultrasound devices. The echogenicity ratio (symptomatic/asymptomatic side) of two ultrasound devices was compared.

Results

A significant difference existed between the symptomatic shoulder and contralateral asymptomatic shoulder (p < 0.001) on the mean gray-level value measurements of each device. The symptomatic-to-asymptomatic tendon echogenicity ratio of device A was 0.919 ± 0.090 in the transverse plane and 0.937 ± 0.081 in the longitudinal plane, and the echogenicity ratio of device B was 0.899 ± 0.113 in the transverse plane and 0.940 ± 0.113 in the longitudinal plane.

Conclusions

The decline of the mean gray-level value and the echogenicity ratio of the supraspinatus tendon in the painful shoulder may be utilized as a useful sonographic reference of unilateral rotator cuff lesions.

Level of evidence

Diagnostic level III.

     

Prone equals prone? Impact of positioning techniques on respiratory function in anesthetized and paralyzed healthy children

Objectives

Although the prone position is effectively used to improve oxygenation, its impact on functional residual capacity is controversial. Different techniques of body positioning might be an important confounding factor. The aim of this study was to determine the impact of two different prone positioning techniques on functional residual capacity and ventilation distribution in anesthetized, preschool-aged children.

Design

Functional residual capacity and lung clearance index, a measure of ventilation homogeneity, were calculated using a sulfur-hexafluoride multibreath washout technique. After intubation, measurements were taken in the supine position and, in random order, in the flat prone position and the augmented prone position (gel pads supporting the pelvis and the upper thorax).

Setting

Pediatric anesthesia unit of university hospital.

Patients and participants

Thirty preschool children without cardiopulmonary disease undergoing elective surgery.

Measurements and results

Mean (range) age was 48.5 (24–80) months, weight 17.2 (10.5–26.9)?kg, functional residual capacity (mean ±?SD) 22.9?±?6.2?ml.kg ^?1 in the supine position and 23.3?±?5.6?ml.kg ^?1 in the flat prone position, while lung clearance indices were 8.1?±?2.3 vs. 7.9?±?2.3, respectively. In contrast, functional residual capacity increased to 27.6 ± 6.5 ml.kg ^?1 (pp

Conclusions

Functional residual capacity and ventilation distribution were similar in the supine and flat prone positions, while these parameters improved significantly in the augmented prone position, suggesting that the technique of prone positioning has major implications for pulmonary function.

     

Retrospective Evaluation of a Fixed-Dose Combination of Oxycodone and Acetaminophen to Manage Moderate Pain: The Lower the Better

Introduction

Oxycodone is one of the most commonly used opioid analgesics in the clinical management of pain. The present retrospective analysis aimed to determine the dose of oxycodone that could achieve effective control of moderate pain when combined with a fixed dose of acetaminophen, and the time required to reach a clinically relevant reduction in intensity of pain.

Methods

Data of patients treated with a combination of oxycodone (5, 10, and 20 mg) and acetaminophen (325 mg) were evaluated for gender, current disease condition, basal pain intensity, total daily dose, days of controlled pain at the initial low dose, and pain intensity after treatment using a numeric pain rating scale.

Results

Data from a total of 491 patients were assessed; of these 93.5% of patients experienced persistent non-cancer pain and had an average baseline pain score of 5.68 ± 1.35. For the overall population, the pain score was reduced to 2.49 ± 1.71 with a mean dose of 8.68 ± 4.96 mg oxycodone after 21.60 ± 6.12 days of treatment with the combination. Almost 97% of the patients who reported relief of pain received 1.61 ± 0.67 doses of oxycodone 5 mg combined with 325 mg of acetaminophen.

Conclusion

A low-dose combination of oxycodone with acetaminophen can be effective in the management of moderate pain and may help in reducing the treatment-associated adverse reactions and drug dependence.

Funding

Sponsorship for article processing charges was provided by Molteni Farmaceutici, Florence, Italy.

     

Association of Performance Status and Pain in Metastatic Bone Pain Management in the Spanish Clinical Setting

Introduction

Bone metastasis is the most common cause of cancer-related pain, and metastatic bone pain (MBP) is not only severe but also progressive in many patients. The aim of this study was to investigate the association between pain management and performance status in patients with metastatic bone cancer in the Spanish clinical setting.

Methods

A 3-month follow-up prospective, epidemiologic, multicenter study was conducted in 579 patients to assess the evolution of their performance, the impact of pain control on sleep and functionality, and the degree of pain control according to analgesic treatment.

Results

In patients with MBP, Eastern Cooperative Oncology Group (ECOG) status (1.5 ± 0.7–1.3 ± 0.7 and 1.3 ± 0.8; p < 0.001) and pain (6.5 ± 1.4–2.8 ± 1.9 and 2.1 ± 1.9; p < 0.001) improved significantly from baseline to months 1 and 3, as did functionality and sleep, after a treatment change consisting of increasing the administration of opioids. Evolution of ECOG and pain were closely related. ECOG and pain outcomes were significantly more favorable in patients treated with opioids versus non-opioid treatment, and in patients who did not need rescue medication versus those who did.

Conclusions

MBP is currently poorly managed in Spain. ECOG improvement is closely and directly related to pain management in MBP. Opioid treatment and a lack of requirements for rescue medication are associated with better ECOG and pain outcomes in MBP patients.

Funding

Mundipharma Pharmaceuticals S.L.

     

Shear wave elastography of the spleen: evaluation of spleen stiffness in healthy volunteers

Purpose

The aim of this study was to assess the mean value of spleen stiffness measured by Shear wave elastography in healthy patients and its dependence on age, sex, and spleen dimensions, and to evaluate the repeatability of this method.

Methods

The final study group included 59 healthy volunteers without any clinical evidence of liver disease, portal hypertension, hematological disorders, and without any pathological ultrasonographic spleen findings. Each patient underwent abdominal ultrasound examination and elastography of the liver and the spleen.

Results

The mean value of spleen stiffness was 16.6 ± 2.5 kPa. In the group of men (N = 25), it was 17.3 ± 2.7 kPa, and in the group of women (N = 34), it was 16.1 ± 2.2 kPa. The study confirmed no correlation between spleen stiffness and sex, age of patients, and spleen size. Coefficient of repeatability and correlation coefficient between the results of the first and the second measurement showed good but not ideal repeatability of the measurement results.

Conclusion

Our outcomes may be a reference point for evaluating spleen stiffness in research on patients with various illnesses.

     

Additive Intraocular Pressure Lowering Effects of the Rho Kinase Inhibitor,Ripasudil in Glaucoma Patients Not Able to Obtain Adequate Control After Other Maximal Tolerated Medical Therapy

Introduction

The aim of this study is to investigate the additive intraocular pressure (IOP)-lowering effects and safety of the selective Rho kinase inhibitor, 0.4% ripasudil, in patients with glaucoma not adequately controlled by other maximal tolerated medical therapies.

Methods

We retrospectively reviewed 92 glaucoma patients who received ripasudil as an additive glaucoma treatment. In spite of receiving prior maximal tolerated medical therapies, all patients had uncontrolled glaucoma before receiving ripasudil. IOP was recorded at all follow-up dates.

Results

The study population consisted of 43 primary open-angle glaucoma (POAG), 28 normal-tension glaucoma (NTG), ten secondary glaucoma, seven exfoliation glaucoma, and four developmental glaucoma patients. After ripasudil administration, there was a significant decrease in the IOP. The mean pre-administration IOP and % IOP reduction at the last follow-up were 19.7 ± 4.9 mmHg and 6.5 ± 17.0% for POAG, 15.5 ± 2.0 mmHg and 2.3 ± 10.4% for NTG, 22.8 ± 8.3 mmHg and 19.1 ± 13.5% for secondary glaucoma, 22.5 ± 4.4 mmHg and 2.1 ± 14.5% for exfoliation glaucoma, and 20.2 ± 8.9 mmHg and 11.4 ± 23.1% for developmental glaucoma, respectively. Side effects led to ripasudil discontinuation in 13 patients, with five exhibiting an allergic reaction, six developing blepharitis, and two having a burning sensation.

Conclusions

Use of ripasudil as an adjunctive therapy resulted in lowering of the IOP. Ripasudil was well tolerated.

Funding

Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (26462689).

     

Shear wave elastography evaluation in pediatric testicular microlithiasis: a comparative study

Purpose

The aim of this study was to evaluate the testicular parenchyma in pediatric patients with testicular microlithiasis by shear wave elastography (SWE) and compare the values with normal control subjects.

Methods

Twenty-three patients previously diagnosed with testicular microlithiasis under follow-up for 20 ± 11 months were included in the study group. In the control group, 31 patients with no medical history that could affect testicular tissue were prospectively included. Forty-six testes in the study group and 62 testes in the control group were evaluated with gray-scale ultrasound and SWE.

Results

There were no differences in age and testes volume between the study and control groups. The mean SWE values of all testes based on elasticity and speed parameters in the study group were 8.84 ± 2.86 kPa and 1.66 ± 0.26 m/s, respectively. In the control group, mean SWE values were 5.26 ± 1.17 kPa and 1.31 ± 0.14 m/s, respectively. Elasticity values were significantly higher in testes with microlithiasis as compared with the control group (p < 0.001).

Conclusions

SWE evaluation demonstrates the effects of ultrastructural changes in elasticity that are not detected on gray-scale ultrasound. SWE is a more reliable method in follow-up examinations for pediatric testicular microlithiasis.

     

Human Radiation Dosimetry of [<Superscript>18</Superscript>F]AV-1451(T807) to Detect Tau Pathology

Purpose

[¹⁸F]AV-1451 is a positron emission tomography (PET) radioligand for detecting paired helical filament tau. Our aim was to estimate the radiation dose of [¹⁸F]AV-1451 in humans.

Procedures

Whole-body PET scans were acquired for six healthy volunteers (three male, three female) for 128 min after injection of [¹⁸F]AV-1451 (268?±?31 MBq). Radiation doses were estimated using the OLINDA/EXM software.

Results

The estimated organ doses ranged from 7.81 to 81.2 μSv/MBq. The critical organ for radiation burden was the liver. Radiation doses to the reproductive and blood-forming organs were 14.15, 8.43, and 18.35 μSv/MBq for the ovaries, testes, and red marrow, respectively. The mean effective dose was 22.47?±?3.59 μSv/MBq.

Conclusions

A standard single injection of 185 MBq (5 mCi) results in an effective dose of 4.7 mSv in a healthy subject. Therefore, [¹⁸F]AV-1451 could be used in multiple PET scans of the same subject per year.