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Jeremy A Adler,1 Neona M Lotz2 1Pacific Pain Medicine Consultants, Encinitas, 2Cypress Ambulatory Surgery Center, Santa Maria, CA, USA Objective: Physician assistants (PAs), nurse practitioners (NPs), and registered nurses (RNs) provide professional services on pain management teams. This review provides an overview of the practical management of chronic pain with intrathecal (IT) therapy using an interprofessional approach (eg, physicians and other health care professionals), with a focus on the contributions of PAs, NPs, and RNs.Methods: Narrative review based on literature searches of the Medline database and treatment guidelines on the use of IT therapy in the management of patients with chronic pain.Results: The specific roles and responsibilities of PAs, NPs, and RNs in the management of patients receiving IT therapy vary by practice. In many pain treatment centers, PAs, NPs, and RNs are responsible for patient education, postimplant maintenance, and ongoing supportive care of patients receiving IT therapy. Topics that we address include patient selection, patient expectations and goal setting, medication selection, outcome assessment, and treatment adjustment. Currently, morphine and ziconotide (a nonopioid, selective N-type calcium channel blocker) are the only agents approved by the US Food and Drug Administration for IT analgesia. We provide relevant information on the dosing, titration, and adverse effect management of these medications for PAs, NPs, and RNs responsible for administering IT therapy.Conclusion: PAs, NPs, and RNs are valuable members of IT pain management teams. Treatment success requires ongoing monitoring of efficacy and adverse effects, with corresponding adjustments to medication selection and dosing, in addition to good communication among the health care professionals involved in patient care. Keywords: chronic pain, implantable drug delivery system, morphine, patient education, ziconotide

Decreased activity and expression of the G-protein coupled receptor GPR88 is linked to many behavior-linked neurological disorders. Published preclinical GPR88 allosteric agonists all have in vivo pharmacokinetic properties that preclude their progression to the clinic, including high lipophilicity and poor brain penetration. Here, we describe our attempts to improve GPR88 agonists' drug-like properties and our analysis of the trade-offs required to successfully target GPR88's allosteric pocket. We discovered two new GPR88 agonists: One that reduced morphine-induced locomotor activity in a murine proof-of-concept study, and the atropoisomeric BI-9508, which is a brain penetrant and has improved pharmacokinetic properties and dosing that recommend it for future in vivo studies in rodents. BI-9508 still suffers from high lipophilicity, and research on this series was halted. Because of its utility as a tool compound, we now offer researchers access to BI-9508 and a negative control free of charge via Boehringer Ingelheim's open innovation portal opnMe.com.

Introduction: Diverticulitis is among the most common abdominal disorders. The best treatment strategy for this complicated disease as well as for recurrent stages is still under debate. Moreover, little knowledge exists regarding the effect of different therapeutic strategies on the health-related quality of life (HrQoL). Therefore, the PREDIC-DIV (PREDICtors for health-related quality of life after elective sigmoidectomy for DIVerticular disease) study aims to assess predictors of a change in HrQoL in patients after elective sigmoidectomy for diverticular disease., Methods and Analysis: A prospective multicentre transnational observational study was started in November 2017. Patients undergoing elective sigmoid resection for diverticular disease were included. Primary outcome includes HrQoL 6 months postoperatively, staged by the Gastrointestinal Quality of Life Index (GIQLI). Secondary outcomes include HrQoL 6 months after sigmoidectomy, assessed using the Short Form 36 Questionnaire and a custom-made Visual Analogue Scale-based inventory; HrQoL after 12 and 24 months; postoperative morbidity; mortality; influence of surgical technique (conventional laparoscopic multiport operation vs robotic approach); histological grading of inflammation and morphological characteristics of the bowel wall in the resected specimen; postoperative functional changes (faecal incontinence, faecal urge, completeness of emptying, urinary incontinence, sexual function); disease-specific healthcare costs; and changes in economic productivity, measured by the iMTA Productivity Cost Questionnaire. The total follow-up will be 2 years., Ethics and Dissemination: The protocol was approved by the medical ethical committee of the Bavarian Medical Council (report identification number: 2017-177). The study was conducted in accordance with the Declaration of Helsinki. The findings of this study will be submitted to a peer-reviewed journal ( BMJ Open , Annals of Surgery , British Journal of Surgery , Diseases of the Colon and the Rectum ). Abstracts will be submitted to relevant national and international conferences., Trial Registration Number: The study is registered with the ClinicalTrials.gov register as NCT03527706; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Although lipid-lowering drugs, especially statins, and recently also PCSK9 inhibitors can reduce LDL cholesterol (LDL-C) and decrease the risk for cardiovascular disease (CVD) including coronary artery disease (CAD) events most efficiently, only 5-10% of high-risk cardiovascular patients reach the target values recommended by international guidelines. In patients who cannot be treated adequately by drugs it is possible to reduce increased LDL-C and/or lipoprotein(a) (Lp(a)) values by the use of lipoprotein apheresis (LA) with the potential to decrease severe CVD events in the range of 70%->80%. Even in Germany, a country with well-established reimbursement guidelines for LA, knowledge about this life-saving therapy is unsatisfactory in medical disciplines treating patients with CVD. Starting in 1996 our aim was to offer LA treatment following current guidelines for all patients in the entire region of our clinic as standard of care., Methods: Based on the experience of our large apheresis competence center overlooking now nearly 80,000 LA treatments in the last two decades, we depict the necessary structure for identification of patients, defining indication, referral, implementation and standardisation of therapy as well as for reimbursement. LA is unfamiliar for most patients and even for many practitioners and consultants. Therefore nephrologists performing more than 90% of LA in Germany have to form a network for referral and ongoing medical education, comprising all regional care-givers, general practitioners as well as the respective specialists and insurances or other cost bearing parties for offering a scientifically approved therapeutic regimen and comprehensive care. The German Lipid Association (Lipid-Liga) has implemented the certification of a lipidological competence center as an appropriate way to realize such a network structure., Results: Working as a lipidological and apheresis competence center in a region of 400,000 to 500,000 inhabitants, today we treat 160 patients in the chronic LA program. In spite of the availability of PCSK9 inhibitors since 2015, LA has remained as an indispensable therapeutic option for targeted lipid lowering treatment. An analysis of nearly 37,000 LA treatments in our own center documented a >80% reduction of cardiovascular events in patients treated by regular LA when comparing with the situation before the start of the LA therapy. We have implemented the concept of an apheresis competence center characterised by ongoing medical education with a focus on lipidological and cardiovascular aspects, interdisciplinary networking and referral., Conclusions: Incidence and prevalence of LA patients in our region demonstrate that based on our ongoing patient-centered approach the access of patients in need to LA is substantially above the German average, thus contributing to an extraordinary reduction of cardiovascular events in the population we in particular feel responsible for., (Copyright © 2019. Published by Elsevier B.V.)

Background: Numerous healthcare studies have shown that more than 90% of all patients with dyslipidaemia are not treated adequately., Objectives: The "Deutsche Gesellschaft zur Bekämpfung von Fettstoffwechselstörungen und ihren Folgeerkrankungen (DGFF)" [German Society of Lipidology], a non-profit professional membership organization, has already made a series of efforts to improve the care of patients suffering from dyslipidaemia. A recent outcome is the nationwide implementation and certification of Lipidological Competence Centres and Networks (LCCNs)., Methods and Results: By involving numerous external medical cooperation partners and combining the detailed work of different in-house medical specialists, the Medical Care Centre Kempten-Allgäu was able to improve both the diagnosis and treatment of patients exhibiting disorders of lipid metabolism (DLM). This local lipidological network is so successful, that it may serve as a nationwide standard model for outpatient lipidological care. Detailed organizational structures for improved lipidological care which are suitable to provide a template for future guidelines for the certification of LCCNs have been developed by the Medical Care Centre Kempten-Allgäu. Stringent requirements of implementation with respect to medical staff, content and structure, staff training, patient education and public relations as well as to documentation, quality assurance and quality improvement must be fulfilled both by the lipidological competence centre (LCC) and the cooperation partners within the lipidological network (LN). Finally, members of the health care system (e.g. health policy and health insurances) should be involved in this attempt and convinced of financial support., Conclusion: The implementation and certification of national LCCNs supported by DGFF could contribute to a comprehensive improvement in the care of patients with dyslipidaemia, resulting in prevention of cardiovascular diseases and reduction of cardiovascular sequelae., (Copyright © 2017. Published by Elsevier B.V.)

LDL cholesterol (LDL-C) and lipoprotein(a) (Lp(a)) are main risk factors for cardiovascular disease (CVD). Efficacy, safety, and tolerability of lipoprotein apheresis (LA) were investigated in 36,745 LA treatments of 118 patients with CVD in a retrospective, monocentric study. Indications were severe hypercholesterolemia (n = 83) or isolated Lp(a) hyperlipoproteinemia (n = 35). Average age of patients at start of LA treatment was 58.1 years for males and 62.5 years for females. Medium interval between the first cardiovascular event and LA treatment was 6.4 ± 5.6 years and the average LA treatment period was 6.8 ± 4.9 years. On average treatments were performed once a week, via peripheral venous access in 79.3% of non-hemodialysis patients. In patients with hypercholesterolemia initial pre-LA LDL-C was lowered from 176.4 ± 67.0 mg/dL by 66.7 ± 10.8% per session, achieving a long-term interval mean value of 119.8 ± 34.7 mg/dL, i.e. reduction by 32.1 ± 19.6% (p < 0.0001). In patients with isolated elevated Lp(a) initial pre-LA Lp(a) was lowered from 127.2 ± 67.3 mg/dL by 66.8 ± 5.8% per session, achieving a long-term interval mean value of 60.0 ± 19.5 mg/dL, i.e. reduction by 52.8 ± 23.0% (p < 0.0001). After start of LA the average annual rate of major adverse coronary events (MACE) of all patients declined by 79.7% (p < 0.0001). Subgroup analysis showed decline by 73.7% (p < 0.0001) in patients with severe hypercholesterolemia, and by 90.4% (p < 0.0001) in patients with isolated elevated Lp(a). Adverse events (AE) occurred in 1.1% of treatments. LA treatment of patients with high risk for CVD due to LDL and/or Lp(a) hyperlipoproteinemia was effective, safe, and well tolerated. The number of cardiovascular events, at least during a six-year period, declined by 80%., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) (Lp(a)) are established causal risk factors for cardiovascular disease (CVD). Efficacy, safety, and tolerability of lipoprotein apheresis (LA) were investigated in 118 patients with CVD covering a period with 36,745 LA treatments in a retrospective, monocentric study. Indications for LA were severe hypercholesterolemia (n = 83) or isolated Lp(a) hyperlipoproteinemia (Lp(a)-HLP) (n = 35). In patients with hypercholesterolemia, initial pre-LA LDL-C was 176.4 ± 67.0 mg/dL. In patients with isolated Lp(a)-HLP, initial pre-LA Lp(a) was 127.2 ± 67.3 mg/dL. Mean reduction rates of LA were 67 % for both LDL-C and Lp(a). During chronic LA, the average annual rate of major adverse cardiac events of all patients declined by 79.7 % (p < 0.0001). Subgroup analysis showed decline by 73.7 % (p < 0.0001) in patients with severe hypercholesterolemia, and by 90.4 % (p < 0.0001) in patients with isolated Lp(a)-HLP. Adverse events occurred in 1.1 % of treatments. LA treatment of patients with a high risk for CVD due to hypercholesterolemia and/or Lp(a)-HLP demonstrated clinical benefit and was safe and well tolerated.

Efficient modes of extracorporeal blood purification are available today for apheresis treatment of progressive atherosclerosis, autoimmune disease, or for improving hemorheology. Advanced technology and sophisticated care render apheresis treatment selective, safe and tolerable. Our task is to constantly update indications for apheresis based on best evidence available and good clinical practice, as well as, to determine how apheresis therapy can be made available to those in need or with otherwise refractory disease. Presenting examples of lipid apheresis, rheopheresis, or immunoadsorption for treatment of hypercholesterolemia, hyperlipoproteinemia (a), acute hearing loss, refractory or exacerbating multiple sclerosis, we highlight real world obstacles for implementation of treatment, resulting in still too many patients with proven or recommended indication left untreated. Based on the experience of the largest apheresis center in Germany, with more than 3,300 treatments per year, we depict the necessary structure for identification of patients, defining indication, referral, implementation of therapy, and reimbursement. Apheresis is unfamiliar to most patients and many practitioners or consultants. Nephrologists, performing >90% of apheresis treatments in Germany, have to form a network for referral comprising all regional care-givers, general practitioners as well as the respective specialists (mainly, cardiologists, endocrinologists, diabetologists, ORL specialists, neurologists, ophthalmologists, or rheumatologists), and insurances or other cost-bearing parties for offering a scientifically approved therapeutic regimen and comprehensive care. We have realized this concept in a high volume apheresis center acting in a closely knit network characterized by an unrelenting effort at ongoing medical education. As a consequence, we include approximately 10 times more patients with appropriate diagnoses in our apheresis program as compared to the national average., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

Purpose: The time-dependent mechanical behavior of common suture materials may have a pronounced influence on the quality of flexor tendon repairs with respect to gap formation., Methods: Sutures commonly used in plastic surgery, particularly for hand tendon repair, were tested in tension for analysis of stress relaxation and creep properties. The three materials tested were (1) Prolene, a monofilament polypropylene(Ethicon, Somerville, NJ); (2) Ethilon, a monofilament nylon(Ethicon, Somerville, NJ); and (3) Ticron, a braided polyester fiber (Sherwood, Davis & Geck, St. Louis, MO). All measurements were made with 1.5-mm (4-0) varieties of the sutures, in physiological buffered solution (0.9% phosphate-buffered saline [PBS]) at both room (22 degrees C) and body temperature (37 degrees C) conditions., Results: Ticron was the stiffest suture at both room and body temperature, followed by Prolene and Ethilon. Both Prolene and Ethilon showed statistically (p< .05) reduced stiffness at body temperature. Prolene exhibited statistically larger (p< .05) relaxation and creep ratios than the other two sutures, and it was the only material to show temperature effects in creep and relaxation., Conclusions: Based on static and viscoelastic mechanical properties, Ticron is the most suitable suture for flexor tendon repairs when compared to Prolene and Ethilon.

Unlabelled: In cardiac SPECT, specificity is significantly affected by artifacts due to photon absorption. As the success of attenuation correction depends mainly on high-quality attenuation maps, SPECT low-dose CT devices are promising. We wanted to evaluate the usefulness of a SPECT low-dose CT device in myocardial perfusion scintigraphy. For the evaluation of attenuation correction systems, primarily comparisons with coronary angiography are used. Because the comparison of a method showing myocardial perfusion with an investigation displaying the morphology of vessels yields some difficulties, we chose perfusion PET with (13)N-ammonia as the reference method., Methods: We prospectively analyzed 23 patients (6 women, 17 men) with known or suspected coronary artery disease. Rest studies and studies under pharmacologic stress with adenosine were performed. After simultaneous injection of (13)N-ammonia and (99m)Tc-sestamibi, a dynamic PET acquisition was started. The SPECT study was performed about 2 h later. Based on 20-segment polar maps, SPECT with and without attenuation correction was compared with PET-derived perfusion values and ammonia uptake values. The PET uptake images were also smoothed to adjust their resolution to the resolution of the SPECT images., Results: The concordance of SPECT and PET studies was improved after attenuation correction. The main effect was seen in the inferior wall. Especially in the apex and anterolateral wall, there were differences between SPECT and PET studies not attributable to attenuation artifacts. Because these differences diminished after smoothing of the PET studies, they might be due to partial-volume effects caused by the inferior resolution of the SPECT images., Conclusion: The x-ray-derived attenuation correction leads to SPECT images that represent myocardial perfusion more accurately than nonattenuation-corrected SPECT images. The benefit of the method is seen primarily in the inferior wall. The low resolution of the SPECT system may lead to artifacts due to partial-volume effects. This phenomenon must be considered when perfusion PET is used as a reference method to investigate the effect of attenuation correction.