Treatment Persistence and Healthcare Costs Among Patients with Rheumatoid Arthritis Changing Biologics in the USA

Introduction

After a patient with rheumatoid arthritis (RA) fails tumor necrosis factor inhibitor (TNFi) treatment, clinical guidelines support either cycling to another TNFi or switching to a different mechanism of action (MOA), but payers often require TNFi cycling before they reimburse switching MOA. This study examined treatment persistence, cost, and cost per persistent patient among MOA switchers versus TNFi cyclers.

Methods

This study of Commercial and Medicare Advantage claims data from the Optum Research Database included patients with RA and at least one claim for a TNFi (adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab) between January 2012 and September 2015 who changed to another TNFi or a different MOA therapy (abatacept, tocilizumab, or tofacitinib) within 1 year. The index date was the date of the change in therapy. Treatment persistence was defined as no subsequent switch or 60-day gap in therapy for 1 year post-index. RA-related costs included plan-paid and patient-paid amounts for inpatient, outpatient, and pharmacy claims. Medication costs included index and post-index costs of TNFi and different MOA therapies.

Results

There were 581 (38.3%) MOA switchers and 935 (61.7%) TNFi cyclers. The treatment persistence rate was significantly higher for MOA switchers versus TNFi cyclers (47.7% versus 40.2%, P = 0.004). Mean 1-year healthcare costs were significantly lower among MOA switchers versus TNFi cyclers for total RA-related costs ($37,804 versus $42,116; P < 0.001) and medication costs ($29,001 versus $34,917; P < 0.001). When costs were divided by treatment persistence, costs per persistent patient were lower among MOA switchers versus TNFi cyclers: $25,436 lower total RA-related cost and $25,999 lower medication costs.

Conclusion

MOA switching is associated with higher treatment persistence and lower healthcare costs than TNFi cycling. Reimbursement policies that require patients to cycle TNFi before switching MOA may result in suboptimal outcomes for both patients and payers.

Funding

Sanofi and Regeneron Pharmaceuticals.

     

Clinical Outcomes and Biologic Costs of Switching Between Tumor Necrosis Factor Inhibitors in US Veterans with Rheumatoid Arthritis

Introduction

The purpose of this study was to evaluate clinical outcomes and drug/administration costs of treatment with tumor necrosis factor inhibitor (TNFi) agents in US veterans with rheumatoid arthritis (RA) initiating TNFi therapy. The analysis compared patients initiating and continuing a single TNFi with patients who subsequently switched to a different TNFi.

Methods

Data from patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry who initiated treatment with adalimumab, etanercept, or infliximab from 2003 to 2010 were analyzed. Outcomes included duration of therapy, Disease Activity Score based on 28 joints (DAS28), and direct drug and drug administration costs.

Results

Of 563 eligible patients, 262 initiated a single TNFi therapy, 142 restarted their initial TNFi after a ≥90-day gap in treatment (interrupted therapy), and 159 switched to a different TNFi. Patients who switched had higher mean DAS28 before starting TNFi therapy than patients with single or interrupted therapy: 5.3 vs 4.5 or 4.6, respectively. Mean duration of the first course was 34.3 months for single therapy, 18.3 months for interrupted therapy, and 17.7 months for switched therapy. Mean post-treatment DAS28 was highest for patients who switched TNFi. Mean annualized costs for first course were $13,800 for single therapy, $13,200 for interrupted therapy, and $14,200 for switched therapy; mean annualized costs for second course were $12,800 for interrupted therapy and $15,100 for switched therapy.

Conclusion

Patients who switched TNFi had higher pre-treatment DAS28 and higher overall costs than patients who received the same TNFi as either single or interrupted therapy.

Funding

This research was funded by Immunex Corp., a fully owned subsidiary of Amgen Inc., and by VA HSR&D Grant SHP 08-172.

     

Impact of Treatment-Related Beliefs on Medication Adherence in Immune-Mediated Inflammatory Diseases: Results of the Global ALIGN Study

Introduction

Medication adherence is critical in chronic immune-mediated inflammatory diseases (IMIDs) and could be affected by patients’ treatment-related beliefs. The objective of this study was to determine beliefs about systemic medications in patients with IMIDs and to explore the association of those beliefs and other factors with adherence.

Methods

This was a multi-country, cross-sectional, self-administered survey study. Included were adults diagnosed with one of six IMIDs receiving conventional systemic medications and/or tumor necrosis factor inhibitors (TNFi). Patients’ necessity beliefs/concerns towards and adherence to treatments were assessed by the Beliefs about Medicines Questionnaire and four-item Morisky Medication Adherence Scale. Correlation of patients’ beliefs about treatment and other factors with adherence were evaluated by multivariable regression analyses.

Results

Among studied patients (N = 7197), 32.0% received TNFi monotherapy, 27.7% received TNFi–conventional combination therapy, and 40.3% received conventional medications. Across IMIDs, high adherence to systemic treatment was more prevalent in TNFi groups (61.3–80.7%) versus corresponding conventional treatment groups (28.4–64.7%). In at least four IMIDs, greater perception of the illness continuing forever (P < 0.001), of the treatment helping (P < 0.001), and more concerns about the illness (P < 0.01), but not clinical parameters, were associated with higher treatment necessity beliefs. Higher treatment necessity beliefs, older age, Caucasian race, and TNFi therapy were associated with high medication adherence in at least four IMIDs.

Conclusions

Treatment necessity beliefs were higher than concerns about current medication in patients with IMID. Illness perceptions had a greater impact on treatment necessity beliefs than clinical parameters. Older age, greater treatment necessity beliefs, and TNFi therapy were associated with high self-reported medication adherence in at least four IMIDs.

Trial registration

ACTRN12612000977875.

Funding

AbbVie.

     

Intraoperative Molecular Imaging of Lung Adenocarcinoma Can Identify Residual Tumor Cells at the Surgical Margins

Purpose

During lung surgery, identification of surgical margins is challenging. We hypothesized that molecular imaging with a fluorescent probe to pulmonary adenocarcinomas could enhance residual tumor during resection.

Procedures

Mice with flank tumors received a contrast agent targeting folate receptor alpha. Optimal dose and time of injection was established. Margin detection was compared using traditional methods versus molecular imaging. A pilot study was then performed in three humans with lung adenocarcinoma.

Results

The peak tumor-to-background ratio (TBR) of murine tumors was 3.9. Fluorescence peaked at 2 h and was not improved beyond 0.1 mg/kg. Traditional inspection identified 30 % of mice with positive margins. Molecular imaging identified an additional 50 % of residual tumor deposits (p?<?0.05). The fluorescent probe visually enhanced all human tumors with a mean TBR of 3.5.

Conclusions

Molecular imaging is an important adjunct to traditional inspection to identify surgical margins after tumor resection.

     

Pre-clinical Evaluation of a Cyanine-Based SPECT Probe for Multimodal Tumor Necrosis Imaging

Purpose

Recently we showed that a number of carboxylated near-infrared fluorescent (NIRF) cyanine dyes possess strong necrosis avid properties in vitro as well as in different mouse models of spontaneous and therapy-induced tumor necrosis, indicating their potential use for cancer diagnostic- and prognostic purposes. In the previous study, the detection of the cyanines was achieved by whole body optical imaging, a technique that, due to the limited penetration of near-infrared light, is not suitable for investigations deeper than 1 cm within the human body. Therefore, in order to facilitate clinical translation, the purpose of the present study was to generate a necrosis avid cyanine-based NIRF probe that could also be used for single photon emission computed tomography (SPECT). For this, the necrosis avid NIRF cyanine HQ4 was radiolabeled with ¹¹¹indium, via the chelate diethylene triamine pentaacetic acid (DTPA).

Procedures

The necrosis avid properties of the radiotracer [¹¹¹In]DTPA-HQ4 were examined in vitro and in vivo in different breast tumor models in mice using SPECT and optical imaging. Moreover, biodistribution studies were performed to examine the pharmacokinetics of the probe in vivo.

Results

Using optical imaging and radioactivity measurements, in vitro, we showed selective accumulation of [¹¹¹In]DTPA-HQ4 in dead cells. Using SPECT and in biodistribution studies, the necrosis avidity of the radiotracer was confirmed in a 4T1 mouse breast cancer model of spontaneous tumor necrosis and in a MCF-7 human breast cancer model of chemotherapy-induced tumor necrosis.

Conclusions

The radiotracer [¹¹¹In]DTPA-HQ4 possessed strong and selective necrosis avidity in vitro and in various mouse models of tumor necrosis in vivo, indicating its potential to be clinically applied for diagnostic purposes and to monitor anti-cancer treatment efficacy.

     

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).

     

Adherence to Long-Term Interferon Beta-1b Injection Therapy in Patients with Multiple Sclerosis Using an Electronic Diary

Introduction

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system requiring long-term treatment, which is often hampered by non-adherence to self-applicable therapies, provoking continued disease activity and health care system burdens. This study assessed the influence of a personal digital assistant (PDA) with diary function (n = 339 patients) on persistence and adherence to an interferon beta treatment regimen in comparison to a paper patient diary (n = 330 patients).

Methods

Patients who recently started with subcutaneous injections of interferon beta-1b were recruited in this prospective, non-interventional, national cohort study for an observational period of 2 years after successful completion of the initial dose escalation.

Results

Therapy persistence as assessed by the drop-out rate within 104 weeks was about 50% in both study cohorts. In male patients, the drop-out rate was 10% lower when using a PDA compared to the non-PDA group. Use of a PDA with an injection reminder function increased adherence to the injection schedule (every other day) by a mean of 24.5 injections over 24 months in comparison to use of a PDA without injection reminder function.

Conclusion

Persistence in this study was in the published range of observational MS studies. Furthermore, in male patients continuation of therapy might be positively influenced by use of a PDA, and both female and male patients might benefit from an integrated reminder function. In conclusion, electronic diaries reminding patients of upcoming injections can promote an improved adherence to MS therapy.

Trial registration

ClinicalTrials.gov identifier: NCT00902135.

Funding

Bayer Vital GmbH.

     

Aspekte einer liaisonpsychiatrischen Betreuung von Patienten einer universitären Schmerzambulanz

Background

Owing to a rise of psychosomatic comorbidities, the treatment of psychological disorders, which may negatively impact prognosis and therapy, is increasingly becoming a focus of attention for pain outpatient clinics.

Aim

This study investigates and discusses the advantages of liaison psychiatric care in a university pain clinic.

Methods

In this retrospective study, we investigated all patients who presented to an anaesthesiologically led pain clinic between January and June 2014. The psychiatric history was taken by the liaison psychiatrist of the pain clinic.

Results

In the period investigated, 485 patients were treated as outpatients. A psychiatric diagnosis was present 351 patients (72.4%). The distribution of the diagnoses was comparable with that of a consultation service. Adaptation and affective disorders dominated. The patients were preferentially treated with new generation antidepressants.

Conclusion

The constant presence of a liaison psychiatrist allows for timely, specialised care of pain patients in terms of a multimodal therapeutic approach.

     

Once-Daily Triple Therapy in Patients with COPD: Patient-Reported Symptoms and Quality of Life

Introduction

Directly recorded patient experience of symptoms and health-related quality of life (HRQoL) can complement lung function and exacerbation rate data in chronic obstructive pulmonary disease (COPD) clinical studies. The FULFIL study recorded daily symptoms and activity limitation together with additional patient-reported outcomes of dyspnea and HRQoL, as part of the prespecified analyses. FULFIL co-primary endpoint data have been previously reported.

Methods

FULFIL was a phase III, 24-week, randomized, double-blind, double-dummy, multicenter study comparing once-daily single inhaler triple therapy [fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI)] 100 µg/62.5 µg/25 µg with twice-daily inhaled corticosteroid/long-acting β₂-agonist therapy [budesonide/formoterol (BUD/FOR)] 400 µg/12 µg in patients with symptomatic COPD at risk of exacerbations. A subset participated for 52 weeks. Patient-reported assessments were: Evaluating Respiratory Symptoms in COPD? (E-RS: COPD), St George’s Respiratory Questionnaire (SGRQ) for COPD, COPD Assessment Test (CAT), baseline and transitional dyspnea indices (TDI) and daily and global anchor questions for activity limitation.

Results

FF/UMEC/VI showed greater reductions from baseline in 4-weekly mean E-RS: COPD total and all subscale scores compared with BUD/FOR; differences were statistically significant (P < 0.05) at each time period. FF/UMEC/VI also demonstrated greater improvements from baseline at weeks 4 and 24 in SGRQ domain scores and TDI focal score compared with BUD/FOR. At weeks 4 and 24, improvements greater than the minimal clinically important difference from baseline were observed in CAT score with FF/UMEC/VI, but not BUD/FOR; differences were statistically significant (P ≤ 0.003).

Conclusion

These findings demonstrate sustained daily symptom and HRQoL benefits of FF/UMEC/VI versus BUD/FOR. The inclusion of the CAT may provide data that are readily generalizable to everyday clinical practice.

Trial registration

ClinicalTrials.gov number: NCT02345161.

Funding

GSK.

     

Labrumrekonstruktion – wie ist die Evidenz?

Background

The labrum is a biomechanically important structure of the hip joint. In the event of labral loss the new technique of labral reconstruction is aimed at restoring the anatomy and function of the labrum and thus prevention of joint degeneration.

Objective

The results and evidence relating to labral reconstruction are presented.

Material and methods

The currently available studies were evaluated and the biomechanical and clinical articles on labral reconstruction are discussed.

Results

There are a large number of different indications and surgical variants of this procedure. Biomechanical and clinical studies concerning labral defects show that the situation is improved by a reconstruction.

Discussion

As a result of the small number of cases and the low quality of the publications, there is as yet a lack of clinical evidence concerning this new surgical method. The biomechanical results suggest that reconstruction of a segmental labral defect is plausible for selected cases. Initial clinical results have to be confirmed by further studies in the long term.

     

Once-Daily Triple Therapy in Patients with Advanced COPD: Healthcare Resource Utilization Data and Associated Costs from the FULFIL Trial

Introduction

Chronic obstructive pulmonary disease is associated with a high healthcare resource and cost burden. Healthcare resource utilization was analyzed in patients with symptomatic chronic obstructive pulmonary disease at risk of exacerbations in the FULFIL study. Patients received either once-daily, single inhaler triple therapy (fluticasone furoate/umeclidinium/vilanterol) 100 µg/62.5 µg/25 µg or twice-daily dual inhaled corticosteroid/long-acting beta agonist therapy (budesonide/formoterol) 400 µg/12 µg.

Methods

FULFIL was a phase III, randomized, double-blind, double-dummy, multicenter study. Unscheduled contacts with healthcare providers were recorded by patients in a daily electronic diary; the costs of healthcare resource utilization were calculated post hoc using UK reference costs.

Results

Over 24 weeks, slightly fewer patients who received fluticasone furoate/umeclidinium/vilanterol (169/911; 18.6%) required contacts with healthcare providers compared with budesonide/formoterol (180/899; 20.0%). Over 52 weeks in an extension population, fewer patients who received fluticasone furoate/umeclidinium/vilanterol required unscheduled contacts with healthcare providers compared with budesonide/formoterol (25.2% vs. 32.7%). Non-drug costs per treated patient per year were lower in the fluticasone furoate/umeclidinium/vilanterol group than the budesonide/formoterol group over 24 and 52 weeks (£653.80 vs. £763.32 and £749.22 vs. £988.03, respectively), with the total annualized cost over 24 weeks being slightly greater for fluticasone furoate/umeclidinium/vilanterol than budesonide/formoterol (£1,289.35 vs. £1,267.45).

Conclusions

This healthcare resource utilization evidence suggests that, in a clinical trial setting over a 24- or 52-week timeframe, non-drug costs associated with management of a single inhaler fluticasone furoate/umeclidinium/vilanterol are lower compared with twice-daily budesonide/formoterol.

Trial Registration

ClinicalTrials.gov number: NCT02345161.

Funding

GSK

     

Olanzapine vs haloperidol: treating delirium in a critical care setting

Objective

To compare the safety and estimate the response profile of olanzapine, a second-generation antipsychotic, to haloperidol in the treatment of delirium in the critical care setting.

Design

Prospective randomized trial

Setting

Tertiary care university affiliated critical care unit.

Patients

All admissions to a medical and surgical intensive care unit with a diagnosis of delirium.

Interventions

Patients were randomized to receive either enteral olanzapine or haloperidol.

Measurements

Patient’s delirium severity and benzodiazepine use were monitored over 5 days after the diagnosis of delirium.

Main results

Delirium Index decreased over time in both groups, as did the administered dose of benzodiazepines. Clinical improvement was similar in both treatment arms. No side effects were noted in the olanzapine group, whereas the use of haloperidol was associated with extrapyramidal side effects.

Conclusions

Olanzapine is a safe alternative to haloperidol in delirious critical care patients, and may be of particular interest in patients in whom haloperidol is contraindicated.

     

A Retrospective Cohort Study Comparing Utilization and Costs of Biologic Therapies and JAK Inhibitor Therapy Across Four Common Inflammatory Indications in Adult US Managed Care Patients

Introduction

Biologic therapies are used to treat several inflammatory diseases, including rheumatoid arthritis (RA), psoriasis (PsO), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). Data from a commercial claims database were used to evaluate utilization and cost of biologic treatment for these conditions.

Methods

Data were obtained from the Optum Research Database. Patients were aged 18–63 years with diagnosis of moderate to severe RA, PsO, PsA, and/or AS and first (index) claim for biologics abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, rituximab, tocilizumab, or ustekinumab or non-biologic tofacitinib between March 1, 2011 and February 28, 2013. One-year treatment costs were based on observed paid amounts and used to impute dosing. Treatment patterns (persistence, switching, discontinuing, restarting) were evaluated.

Results

Data from 20,159 patients were analyzed for index medications abatacept (n = 583), adalimumab (n = 6521), certolizumab pegol (n = 415), etanercept (n = 9116), golimumab (n = 231), infliximab (n = 1906), rituximab (n = 295), tocilizumab (n = 165), ustekinumab (n = 922), and tofacitinib (n = 5). For patients with RA only, costs were lowest for tofacitinib ($18,769), rituximab ($19,569), or abatacept ($21,877), and ranged from $23,682 to $30,269 for all other medications. For patients with PsO only, costs were lowest for adalimumab ($29,186), etanercept ($31,212), and infliximab ($32,409) compared with ustekinumab ($53,746). For patients with PsA only, costs were lowest for etanercept ($26,916), followed by golimumab ($27,987), adalimumab ($28,749), and infliximab ($31,974). Costs were lowest with etanercept for RA plus PsA ($25,477) and for PsO plus PsA ($29,376), and with golimumab for AS only ($24,225). Across indications, annual costs were $29,521, $27,488, and $28,672 for adalimumab, etanercept, and infliximab, respectively; persistence was greatest with infliximab (range 66–79%) compared with 11–59% for all other biologics.

Conclusion

One-year treatment costs varied considerably between medications and indications. Some newly approved agents had lower costs but further research is needed to confirm these estimates as more patients are treated.

Funding

Immunex (a wholly owned subsidiary of Amgen Inc.) and Wyeth (acquired by Pfizer).

     

Outcomes of Stable Multiple Sclerosis Patients Staying on Initial Interferon Beta Therapy Versus Switching to Another Interferon Beta Therapy: A US Claims Database Study

Introduction

This study was designed to assess real-world outcomes of patients with multiple sclerosis (MS) who were stable on interferon (IFN) beta therapy in the year prior to switching to another IFN beta therapy versus those who continued on the initial treatment.

Methods

This study used administrative claims from MarketScan Commercial Claims and Encounters Database, from January 1, 2010, to March 31, 2015, to identify MS patients aged 18–64 years who remained relapse free for at least 1 year while continuously treated with an IFN beta therapy. Stable patients remaining on their initial IFN beta therapy (no-switch patients) were matched with stable patients who switched IFN beta therapy (switch patients) using propensity score matching (first claim?=?index date). Outcome measures included annualized relapse rate (ARR), the percentage of patients who relapsed, medication possession ratio, and the proportion of days covered and were measured during the year following the index date.

Results

This study identified 531 patients in the no-switch group and 177 patients in the switch group, with subsets of 270 patients in the no-switch group and 90 patients in the switch group stable on intramuscular (IM) IFN beta-1a therapy. All outcomes during the follow-up year were significantly better in the no-switch group than in the switch group. For all patients, ARR in the switch group was more than twice that in the no-switch group (P?=?0.002). For patients stable on IM IFN beta-1a at baseline, ARR was twice as high in the switch group as in the no-switch group (P?=?0.012).

Conclusion

Among all patients stable on IFN beta therapy and the subset stable on IM IFN beta therapy in particular, those who remained on therapy had significantly better outcomes than those who switched to another IFN beta therapy.

Funding

Biogen (Cambridge, MA, USA).

     

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.

     

Münzkopfschmerz

Background

Subcutaneous peripheral nerve field stimulation (sPNFS) is an established procedure for the treatment of chronic localized neuropathic pain of peripheral origin. The treatment of nummular headache primarily focuses on conservative methods with limited prospects of success. The role of sPNFS in the treatment of nummular headache has not been investigated as yet.

Question

Is the sPNFS an option in the management of nummular headache?

Materials and methods

In addition to a summary of established methods in the treatment of nummular headache, sPNFS as a possible form of therapy is discussed.

Results

A positive effect of sPNFS in terms of the treatment of nummular headache is shown.

Discussion

sPNFS stimulates free subcutaneous nerves and transmits a pleasant form of paraesthesia in the area of pain. If regular conservative therapy has already been exhausted, then sPNFS might be an effective new option in the treatment of nummular headache. sPNFS is a minimally invasive and low-risk procedure. However, the high treatment cost and restrictions regarding fitness to undergo MRI are points of criticism. Further studies are needed to define its potential and role in the treatment of nummular headache.

     

In Vivo HER2-Targeted Magnetic Resonance Tumor Imaging Using Iron Oxide Nanoparticles Conjugated with Anti-HER2 Fragment Antibody

Purpose

The feasibility of iron oxide nanoparticles (IONPs) conjugated with anti-epidermal growth factor receptor 2 (HER2) single-chain antibody (scFv-IONPs) as novel HER2-targeted magnetic resonance (MR) contrast agents was investigated.

Procedures

The scFv-IONPs were prepared and identified. For in vitro MRI, NCI-N87 (HER2 high expression) and SUIT2 (low expression) cells were incubated with scFv-IONPs. For in vivo MRI, NCI-N87 and SUIT2 tumor-bearing mice were intravenously injected with scFv-IONPs and imaged before and 24 h post-injection.

Results

The scFv-IONPs demonstrated high transverse relaxivity (296.3 s^?1 mM^?1) and affinity toward HER2 (K_D?=?11.7 nM). In the in vitro MRI, NCI-N87 cells treated with scFv-IONPs exhibited significant MR signal reduction (44.6 %) than SUIT2 cells (6.8 %). In the in vivo MRI, decrease of MR signals in NCI-N87 tumors (19.3 %) was more notable than that in SUIT2 tumors (6.2 %).

Conclusions

The scFv-IONPs enabled HER2-specific tumor MR imaging, suggesting the potential of scFv-IONPs as a robust HER2-targeted MR contrast agent.

     

A Novel Unsupervised Segmentation Approach Quantifies Tumor Tissue Populations Using Multiparametric MRI: First Results with Histological Validation

Purpose

We aimed to precisely estimate intra-tumoral heterogeneity using spatially regularized spectral clustering (SRSC) on multiparametric MRI data and compare the efficacy of SRSC with the previously reported segmentation techniques in MRI studies.

Procedures

Six NMRI nu/nu mice bearing subcutaneous human glioblastoma U87 MG tumors were scanned using a dedicated small animal 7T magnetic resonance imaging (MRI) scanner. The data consisted of T2 weighted images, apparent diffusion coefficient maps, and pre- and post-contrast T2 and T2* maps. Following each scan, the tumors were excised into 2–3-mm thin slices parallel to the axial field of view and processed for histological staining. The MRI data were segmented using SRSC, K-means, fuzzy C-means, and Gaussian mixture modeling to estimate the fractional population of necrotic, peri-necrotic, and viable regions and validated with the fractional population obtained from histology.

Results

While the aforementioned methods overestimated peri-necrotic and underestimated viable fractions, SRSC accurately predicted the fractional population of all three tumor tissue types and exhibited strong correlations (r_necrotic = 0.92, r_{peri-necrotic} = 0.82 and r_viable = 0.98) with the histology.

Conclusions

The precise identification of necrotic, peri-necrotic and viable areas using SRSC may greatly assist in cancer treatment planning and add a new dimension to MRI-guided tumor biopsy procedures.

     

Effects of the SGLT-2 Inhibitor Empagliflozin on Renal Tissue Oxygenation in Non-Diabetic Subjects: A Randomized,Double-Blind,Placebo-Controlled Study Protocol

Introduction

Empagliflozin is an SGLT-2 inhibitor (SGLT-2i) which belongs to a new class of hypoglycemic drugs with the unique property of decreasing blood glucose independently from insulin, through an increase in glycosuria. In addition to decreasing cardiovascular morbidity and mortality, empagliflozin has nephroprotective properties in high cardiovascular risk patients with type 2 diabetes. Decreased hyperfiltration and shifting towards more favorable renal fuel energetics with improved renal oxygenation may explain some of these properties. With this study, we propose to explore the effects of empagliflozin on renal tissue oxygenation using blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI).

Methods

This is a double-blind, randomized, placebo-controlled study examining the acute and chronic renal effects of empagliflozin 10 mg. The primary outcome is the effects of empagliflozin on renal tissue oxygenation as measured by BOLD-MRI. The secondary outcomes include the effects of empagliflozin on tubular function, 24 h blood pressure control, and the influence of body mass index (BMI) on the renal response to empagliflozin. Fifteen normal weight, 15 overweight, and 15 obese non-diabetic subjects (men and women) will be recruited. Each participant will undergo 24 h urine collections and blood pressure measurements on day ? 1, followed by an investigation day at the study center with blood and urine sampling and renal BOLD-MRI measurements before and 180 min after the administration of 10 mg empagliflozin or placebo. This sequence of measurements will be repeated after 1 month of a daily empagliflozin or placebo intake. To investigate renal oxygenation, the renal cortical and medullary R2*, as a marker of oxygenation, will be assessed by BOLD-MRI under standardized hydration conditions: the higher R2*, the lower oxygenation.

Conclusion

SGLT-2 inhibitors have a profound effect on renal physiology. This is an important study that will explore for the first time whether inhibiting SGLT-2 with empagliflozin in healthy volunteers affects renal tissue oxygenation as determined by BOLD-MRI.

Funding

Boehringer Ingelheim Pharma GmbH & Co.

Trial registration

ClinicalTrials.gov identifier, NCT03093103.