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Introduction: Foslevodopa/foscarbidopa, a soluble formulation of levodopa/carbidopa (LD/CD) prodrugs for the treatment of Parkinson's disease (PD), is administered as a 24-hour/day continuous subcutaneous infusion (CSCI) with a single infusion site. The efficacy and safety of foslevodopa/foscarbidopa versus oral immediate-release LD/CD was previously demonstrated in patients with PD in a 12-week, randomized, double-blind, phase 3 trial (NCT04380142). We report the results of a separate 52-week, open-label, phase 3 registrational trial (NCT03781167) that evaluated the safety/tolerability and efficacy of 24-hour/day foslevodopa/foscarbidopa CSCI in patients with advanced PD. Methods: Male and female patients with levodopa-responsive PD and ≥ 2.5 hours of "Off" time/day received 24-hour/day foslevodopa/foscarbidopa CSCI at individually optimized therapeutic doses (approximately 700–4250 mg of LD per 24 hours) for 52 weeks. The primary endpoint was safety/tolerability. Secondary endpoints included changes from baseline in normalized "Off" and "On" time, percentage of patients reporting morning akinesia, Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Parkinson's Disease Sleep Scale–2 (PDSS-2), 39-item Parkinson's Disease Questionnaire (PDQ-39), and EuroQol 5-dimension questionnaire (EQ-5D-5L). Results: Of 244 enrolled patients, 107 discontinued, and 137 completed treatment. Infusion site events were the most common adverse events (AEs). AEs were mostly nonserious (25.8% of patients reported serious AEs) and mild/moderate in severity. At week 52, "On" time without troublesome dyskinesia and "Off" time were improved from baseline (mean [standard deviation (SD)] change in normalized "On" time without troublesome dyskinesia, 3.8 [3.3] hours; normalized "Off" time, −3.5 [3.1] hours). The percentage of patients experiencing morning akinesia dropped from 77.7% at baseline to 27.8% at week 52. Sleep quality (PDSS-2) and quality of life (PDQ-39 and EQ-5D-5L) also improved. Conclusion: Foslevodopa/foscarbidopa has the potential to provide a safe and efficacious, individualized, 24-hour/day, nonsurgical alternative for patients with PD. Trial Registration Number: ClinicalTrials.gov identifier NCT03781167. [ABSTRACT FROM AUTHOR]

Perioperative lidocaine (lignocaine) infusions are being employed with increasing frequency. The determinants of systemic lidocaine concentrations during prolonged administration are unclear. In the Long-term Outcomes after Lidocaine Infusions for PostOperative Pain (LOLIPOP) pilot trial, the impact of infusion duration and body size metrics on serum lidocaine concentrations was examined with regression models in 48 women undergoing breast cancer surgery. Lidocaine was delivered as an intravenous bolus (1.5 mg/kg) and infusion (2 mg/kg per h) intraoperatively, followed by a 12-h subcutaneous infusion (1.33 mg/kg per h) postoperatively. Dosing was based on total body weight. Wound infiltration with other long-acting local anaesthetics was permitted. Protein binding and pharmacogenomic data were also collected. Lidocaine concentrations (median (interquartile range) (range)) during prolonged administration were in the safe and potentially therapeutic range: post-anaesthesia care unit 2.16 (1.73–2.82) (1.12–6.06) µg/ml; ward 1.41 (1.22–1.75) (0.64–2.81) µg/ml. Concentrations increased non-linearly during the early intravenous phase of administration (mean rise 1.21 µg/ml per hour of infusion, P = 0.007) but reached a pseudo steady-state during the later subcutaneous phase. Higher dose rates received per kilogram of lean (P = 0.004), adjusted (P = 0.006) and ideal body weight (P = 0.009) were associated with higher steady-state concentrations. The lidocaine free fraction was unaffected by the presence of ropivacaine, and phenotypes linked to slow metabolism were infrequent. Serum lidocaine concentrations reached a pseudo steady-state during a 12-h postoperative infusion. Greater precision in steady-state concentrations can be achieved by dosing on lean body weight versus adjusted or ideal body weight (equivalent lean body weight doses: intravenous bolus 2.5 mg/kg; intravenous infusion 3.33 mg/kg per h; subcutaneous infusion 2.22 mg/kg per h. [ABSTRACT FROM AUTHOR]

Abstract Introduction Foslevodopa/foscarbidopa, a soluble formulation of levodopa/carbidopa (LD/CD) prodrugs for the treatment of Parkinson’s disease (PD), is administered as a 24-hour/day continuous subcutaneous infusion (CSCI) with a single infusion site. The efficacy and safety of foslevodopa/foscarbidopa versus oral immediate-release LD/CD was previously demonstrated in patients with PD in a 12-week, randomized, double-blind, phase 3 trial (NCT04380142). We report the results of a separate 52-week, open-label, phase 3 registrational trial (NCT03781167) that evaluated the safety/tolerability and efficacy of 24-hour/day foslevodopa/foscarbidopa CSCI in patients with advanced PD. Methods Male and female patients with levodopa-responsive PD and ≥ 2.5 hours of “Off” time/day received 24-hour/day foslevodopa/foscarbidopa CSCI at individually optimized therapeutic doses (approximately 700–4250 mg of LD per 24 hours) for 52 weeks. The primary endpoint was safety/tolerability. Secondary endpoints included changes from baseline in normalized “Off” and “On” time, percentage of patients reporting morning akinesia, Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Parkinson’s Disease Sleep Scale–2 (PDSS-2), 39-item Parkinson’s Disease Questionnaire (PDQ-39), and EuroQol 5-dimension questionnaire (EQ-5D-5L). Results Of 244 enrolled patients, 107 discontinued, and 137 completed treatment. Infusion site events were the most common adverse events (AEs). AEs were mostly nonserious (25.8% of patients reported serious AEs) and mild/moderate in severity. At week 52, “On” time without troublesome dyskinesia and “Off” time were improved from baseline (mean [standard deviation (SD)] change in normalized “On” time without troublesome dyskinesia, 3.8 [3.3] hours; normalized “Off” time, −3.5 [3.1] hours). The percentage of patients experiencing morning akinesia dropped from 77.7% at baseline to 27.8% at week 52. Sleep quality (PDSS-2) and quality of life (PDQ-39 and EQ-5D-5L) also improved. Conclusion Foslevodopa/foscarbidopa has the potential to provide a safe and efficacious, individualized, 24-hour/day, nonsurgical alternative for patients with PD. Trial Registration Number ClinicalTrials.gov identifier NCT03781167.

Background: As Parkinson's disease (PD) advances, management is challenged by an increasingly variable and inconsistent response to oral dopaminergic therapy, requiring special considerations by the provider. Continuous 24 h/day subcutaneous infusion of foslevodopa/foscarbidopa (LDp/CDp) provides steady dopaminergic stimulation that can reduce symptom fluctuation. Objective: Our aim is to review the initiation, optimization, and maintenance of LDp/CDp therapy, identify possible challenges, and share potential mitigations. Methods: Review available LDp/CDp clinical trial data for practical considerations regarding the management of patients during LDp/CDp therapy initiation, optimization, and maintenance based on investigator clinical trial experience. Results: LDp/CDp initiation, optimization, and maintenance can be done without hospitalization in the clinic setting. Continuous 24 h/day LDp/CDp infusion can offer more precise symptom control than oral medications, showing improvements in motor fluctuations during both daytime and nighttime hours. Challenges include infusion-site adverse events for which early detection and prompt management may be required, as well as systemic adverse events (eg, hallucinations) that may require adjustment of the infusion rate or other interventions. A learning curve should be anticipated with initiation of therapy, and expectation setting with patients and care partners is key to successful initiation and maintenance of therapy. Conclusion: Continuous subcutaneous infusion of LDp/CDp represents a promising therapeutic option for individuals with PD. Individualized dose optimization during both daytime and nighttime hours, coupled with patient education, and early recognition of certain adverse events (plus their appropriate management) are required for the success of this minimally invasive and highly efficacious therapy.

BackgroundPulmonary arterial hypertension occurs as a result of vascular remodeling and dysregulation of endothelial cells that narrows small pulmonary arteries and raises precapillary pressures. Pulmonary arterial hypertension is a rare and progressive disease characterized by dyspnea, chest pain, and syncope. Parenteral treprostinil is indicated for the treatment of pulmonary arterial hypertension to diminish symptoms associated with exercise. Up to 92% of patients treated with treprostinil via subcutaneous delivery experienced infusion site pain and approximately 23% discontinued treatment due to site pain. Cannabidiol salve may have analgesic and anti-inflammatory properties and could be an additional option for patients with infusion site pain.Case reportTwo patients with pulmonary arterial hypertension were treated with cannabidiol salve. Both patients reported a reduction in infusion site pain without the need for narcotics.ConclusionThese two cases suggest that cannabidiol salve may help to minimize redness and alleviate pain at the infusion site. Additional studies are required to test the effectiveness of cannabidiol in a larger group of patients with infusion site pain.

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Patients with diabetes mellitus type 1 depend on exogenous insulin to keep their blood glucose concentrations within the desired range. Subcutaneous bihormonal artificial pancreas devices that can measure glucose concentrations continuously and autonomously calculate and deliver insulin and glucagon infusions is a promising new treatment option for these patients. The slow absorption rate of insulin from subcutaneous tissue is perhaps the most important factor preventing the development of a fully automated artificial pancreas using subcutaneous insulin delivery. Subcutaneous insulin absorption is influenced by several factors, among which local subcutaneous blood flow is one of the most prominent. We have discovered that micro-doses of glucagon may cause a substantial increase in local subcutaneous blood flow. This paper discusses how the local vasodilative effects of micro-doses of glucagon might be utilised to improve the performance of subcutaneous bihormonal artificial pancreas devices. We map out the early stages of our hypothesis as a disruptive novel approach, where we propose to use glucagon as a vasodilator to accelerate the absorption of meal boluses of insulin, besides using it conventionally to treat hypoglycaemia.

What is known and objective: Proton pump inhibitors are potent suppressors of gastric acid secretion, and are commonly prescribed in palliative medicine. Despite multiple relevant indications in patients at the end‐of‐life, their use is often precluded as oral and intravenous administration is frequently inappropriate or not possible. Limited anecdotal evidence suggests proton pump inhibitors may be administered subcutaneously. Our objective was to investigate the tolerability and effectiveness of the administration of esomeprazole as a continuous subcutaneous infusion over 24 h via a syringe driver. Methods: Case series (n = 7) design assessing sequential patients admitted to a specialist inpatient centre for palliative care, who required parenteral proton pump inhibitor therapy. Results and Discussion: Four patients reported complete resolution of dyspeptic and reflux symptoms post commencement of esomeprazole. Two patients developed upper gastrointestinal bleeding, which via observation of vomitus and stools, resolved with the initiation of esomeprazole. A single patient, deemed high risk of gastrointestinal bleeding, was commenced on esomeprazole and no bleeding events occurred. What is new and conclusion: Esomeprazole when administered via a syringe driver over 24 h appears well tolerated and effective for the symptomatic management of dyspepsia and treatment of gastrointestinal bleeding. Overall, this series adds to the limited evidence base for using subcutaneous proton pump inhibitors in the palliative demographic. [ABSTRACT FROM AUTHOR]

Copyright of Enfermería en Cardiologia is the property of Asociacion Espanola de Enfermeria en Cardiologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract Background Cobalamin (cbl)-related remethylation disorders are a heterogeneous group of inherited disorders comprising the remethylation of homocysteine to methionine and affecting multiple organ systems, most prominently the nervous system and the bone marrow. To date, the parenteral, generally intramuscular, lifelong administration of hydroxycobalamin (OHCbl) is the mainstay of therapy in these disorders. The dosage and frequency of OHCbl is titrated in each patient to the minimum effective dose in order to account for the painful injections. This may result in undertreatment, a possible risk factor for disease progression and disease-related complications. Results We describe parenteral administration of OHCbl using a subcutaneous catheter together with a portable infusion pump in a home therapy setting in four pediatric patients with remethylation disorders, two patients with cblC, one patient with cblG, and one patient with cblE deficiency, in whom intramuscular injections were not or no longer feasible. The placement of the subcutaneous catheters and handling of the infusion pump were readily accomplished and well accepted by the patients and their families. No adverse events occurred. The use of a small, portable syringe driver pump allowed for a most flexible administration of OHCbl in everyday life. The concentrations of total homocysteine levels were determined at regular patient visits and remained within the therapeutic target range. This approach allowed for the continuation of OHCbl therapy or the adjustment of therapy required to improve metabolic control in our patients. Conclusions Subcutaneous infusion using a subcutaneous catheter system and a portable pump for OHCbl administration in combined and isolated remethylation disorders is safe, acceptable, and effective. It decreases disease burden in preventing frequent single injections and providing patient independence. Thus, it may promote long-term adherence to therapy in patients and parents.

Background: In recent decades, reducing the size of the drug delivery systems along with precise control of the amount of drug pumped, has attracted the attention of many researchers. Objectives: The slow subcutaneous infusion of the deferoxamine in thalassemia major patients during day is of vital importance either for the drug effectiveness. However, this is difficult to achieve due to the large size of the conventional infusion pumps and their high weight. Therefore, sizeandweight reduction of the infusionpumpsare very important issues thatmustbe well addressed. Methods: Abiomedicalmicropumpfor drug solution infusion tohumanbody based onthe magnetohydrodynamic(MHD)concept is and designed, and its performance experimentally is investigated in this research. The key challenge in the fabrication of the micropump is its size, weight, bubble generation, and high operating voltage. Results: The present design is well responded to these problems. The final design operates with a 1.2 v without any bubble generation, while its size and weight are 20 × 40 × 50 mm3 and 90 grams, respectively. The size of the micropump is about 1/3 size of conventional micropump, while its weight is half of them. Conclusions: Therefore, the newly designed micropump has the ability to inject the drug solution to thalassemia major patients with a sufficient infusion rate during the day without disturbing them, so it can increase their quality of life and increase their life expectancy. [ABSTRACT FROM AUTHOR]

Copyright of Revista de Pesquisa: Cuidado é Fundamental is the property of Revista de Pesquisa: Cuidado e Fundamental Online and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Homozygous/compound heterozygous forms of congenital protein C deficiency are often associated with severe antenatal and postnatal thrombotic or hemorrhagic complications. Protein C deficiency frequently leads to severe adverse outcomes like blindness and neurodevelopmental delay in children and may even lead to death. The most widely used long-term postnatal treatment consists of oral anticoagulation with vitamin K antagonists (e.g., warfarin), which is supplemented with protein C concentrate in acute phases. Subcutaneous infusions have been described in infants mostly from 2 months of age after severe postnatal thrombosis, but not in newborns or premature infants without thromboembolism. We report the first case of a compound heterozygous protein C-deficient preterm infant, born at 31+5 weeks of gestation to parents with heterozygous protein C deficiency (protein C activity 0.9% at birth). We focus on both prenatal and perinatal management including antithrombotic treatment during pregnancy, the cesarean section, and continuous postnatal intravenous and consecutive subcutaneous therapy with protein C concentrate followed by a change of therapy to direct oral anticoagulants (DOACs) (apixaban). We report successful home treatment with subcutaneous protein C concentrate substitution overnight (target protein C activity >25%) without complication up to 12.5 years of age. We propose that early planned cesarean section at 32 or preferably 34 weeks of gestation limits potential maternal side effects of anticoagulation with vitamin K antagonists and reduces fetal thromboembolic complications during late pregnancy. Intravenously administered protein C and early switch to subcutaneous infusions (reaching about 3 kg body weight) resulted in sufficient protein C activity and has guaranteed an excellent quality of life without any history of thrombosis for 13 years now. In older children with protein C deficiency, as in our case, DOACs could be a new therapeutic option.

Although it represents a valid alternative for patients with type 1 diabetes (T1DM) with insufficient glycemic control and/or with recurrent hypoglycemia, insulin pump therapy (Continuous Subcutaneous Insulin Infusion, CSII) in Italy is nowadays still relatively uncommon. The following review aims to investigate the barriers that limit the transition to CSII and the reasons behind the widespread cases of drop-out, particularly evident in younger patients. Among the interventions that could contribute to the solution of the problem, catheter-less insulin pumps (or patch-pumps) will be described: a tool potentially able to reduce, if not eliminate, some of the main obstacles encountered by patients. In particular, a new opportunity has become available today thanks to the evolution of the generation of catheter-less insulin pumps represented by Accu-Chek® Solo (Roche Diabetes Care GmbH), therefore three clinical cases of patients with T1DM undergoing therapy with the Accu-Chek® Solo insulin pump will be presented and discussed herein.

Background: Cobalamin (cbl)-related remethylation disorders are a heterogeneous group of inherited disorders comprising the remethylation of homocysteine to methionine and affecting multiple organ systems, most prominently the nervous system and the bone marrow. To date, the parenteral, generally intramuscular, lifelong administration of hydroxycobalamin (OHCbl) is the mainstay of therapy in these disorders. The dosage and frequency of OHCbl is titrated in each patient to the minimum effective dose in order to account for the painful injections. This may result in undertreatment, a possible risk factor for disease progression and disease-related complications.Results: We describe parenteral administration of OHCbl using a subcutaneous catheter together with a portable infusion pump in a home therapy setting in four pediatric patients with remethylation disorders, two patients with cblC, one patient with cblG, and one patient with cblE deficiency, in whom intramuscular injections were not or no longer feasible. The placement of the subcutaneous catheters and handling of the infusion pump were readily accomplished and well accepted by the patients and their families. No adverse events occurred. The use of a small, portable syringe driver pump allowed for a most flexible administration of OHCbl in everyday life. The concentrations of total homocysteine levels were determined at regular patient visits and remained within the therapeutic target range. This approach allowed for the continuation of OHCbl therapy or the adjustment of therapy required to improve metabolic control in our patients.Conclusions: Subcutaneous infusion using a subcutaneous catheter system and a portable pump for OHCbl administration in combined and isolated remethylation disorders is safe, acceptable, and effective. It decreases disease burden in preventing frequent single injections and providing patient independence. Thus, it may promote long-term adherence to therapy in patients and parents. [ABSTRACT FROM AUTHOR]

Background: Several medical devices have been developed for continuous subcutaneous drug infusion for home palliative care (HPC), such as elastomeric infuser pumps (EIP). There is no evidence on the repeated filling of EIP for continuous subcutaneous delivery for HPC. Aim: A clinical case series report of terminally-ill patients cared for in HPC, with repeated filling of EIPs for home-based subcutaneous medications. Methods: A retrospective analysis of each patient's EIP-related entries in an anonymised database regarding: 1) EIP general functioning aspects; 2) clinical aspects: symptom control and local skin complications. Overall and per-patient cost-saving was also calculated. Findings: A total of 10 cases were analysed (four 50-hour EIP and six 30-hour EIP). All EIPs had a mean number of refillings (standard deviation (SD), mode) of 1.6 ((0.5), 2); with 3.2 drugs on average used in each EIP ((1.4), 4). Approximate total mean (SD) usage time for both types of EIP was 87 (29) hours; and all EIP were used, on average (SD), 49 (23) hours more than its labelled duration. All EIPs showed a complete reservoir deflation between refilling. Only one patient had a minor skin complication and no symptom aggravation was observed, except for two cases with mild anxiety and agitation. Cost-saving analysis for the complete case series showed that EIP refillings saved, on average, €24 per-patient and a total of nearly €240, for both types of infuser pumps. Conclusion: This preliminary study suggests that refilling is safe and reduces cost. Future research on EIP refilling using controlled and systematic methodologies are warranted. [ABSTRACT FROM AUTHOR]

Lidocaine continuous subcutaneous infusion (L-CSCI) for neuropathic pain in hospice patients has limited evidence for its safety and efficacy, and guidelines are lacking. This study assesses a series of patients admitted to a hospice over a six-month period that had neuropathic pain and received L-CSCI. The primary outcome was improvement in patient-rated distress from pain following L-CSCI titration. Also assessed were changes in oral morphine equivalent dose (OME), frequency of breakthrough medication, functional status, adverse effects and perception of response. Fifteen patients received L-CSCI for an average of 6.7 days (range 1–92). Average pain distress score decreased by 2 or more in six patients. Positive responses to L-CSCI were documented in the clinical notes of 10 patients. Opioid down-titration occurred in four patients. Lidocaine levels were performed in 3 patients but did not change management. Five patients experienced adverse effects attributable to lidocaine and all responded to simple measures. In conclusion, L-CSCI can help manage neuropathic pain in hospice patients, particularly in those who cannot swallow oral medications. Further systematic research is warranted to establish efficacy and tolerability, and to inform guideline development. [ABSTRACT FROM AUTHOR]

Background: The use of continuous subcutaneous infusion of drugs using the repeated filling of elastomeric infuser pumps (EIP) has gained clinical recognition for palliative care at home. However, to date, there has been a notable absence of research examining the cost implications associated with the repeated EIP filling procedure. We aimed to evaluate the cost associated to the repeated filling of EIP used in a home-based palliative care team., Methods: We conducted an analysis of the cost associated to the repeated filling of 240 EIP (1-day, n = 136; 2-day, n = 102; 7-day, n = 2) (110 patients)., Results: The refilling procedure led to a reduction in the utilization of 409 devices, resulting in savings of €4.031. EIP refilling did not result in a decrease in the number of home visits, the duration of each visit, the expenses associated with transportation to patients' residences, or the nurse-to-hour cost., Conclusion: Refilling EIPs reduces costs by reducing the number of devices purchased. No additional cost savings were noted in nursing time, number of home visits and duration, and expenses with transportation. Further cost savings could be realized by training laycarers to refill EIP at home independently. Future research should assess the feasibility of laycarers training programs on performing EIP filling at home., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: As Parkinson's disease (PD) advances, management is challenged by an increasingly variable and inconsistent response to oral dopaminergic therapy, requiring special considerations by the provider. Continuous 24 h/day subcutaneous infusion of foslevodopa/foscarbidopa (LDp/CDp) provides steady dopaminergic stimulation that can reduce symptom fluctuation., Objective: Our aim is to review the initiation, optimization, and maintenance of LDp/CDp therapy, identify possible challenges, and share potential mitigations., Methods: Review available LDp/CDp clinical trial data for practical considerations regarding the management of patients during LDp/CDp therapy initiation, optimization, and maintenance based on investigator clinical trial experience., Results: LDp/CDp initiation, optimization, and maintenance can be done without hospitalization in the clinic setting. Continuous 24 h/day LDp/CDp infusion can offer more precise symptom control than oral medications, showing improvements in motor fluctuations during both daytime and nighttime hours. Challenges include infusion-site adverse events for which early detection and prompt management may be required, as well as systemic adverse events (eg, hallucinations) that may require adjustment of the infusion rate or other interventions. A learning curve should be anticipated with initiation of therapy, and expectation setting with patients and care partners is key to successful initiation and maintenance of therapy., Conclusion: Continuous subcutaneous infusion of LDp/CDp represents a promising therapeutic option for individuals with PD. Individualized dose optimization during both daytime and nighttime hours, coupled with patient education, and early recognition of certain adverse events (plus their appropriate management) are required for the success of this minimally invasive and highly efficacious therapy., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Anna Jeong is an employee of AbbVie Inc., and may hold AbbVie Inc. stock and/or stock options. Agnita J. W. Boon is a study investigator and has served as an advisory board member for AbbVie Inc., Stada, and Ever Pharma. She has received a research grant from Stichting ParkinsonFonds and the Erasmus Trust Fund. Amy M. Spiegel is an employee of AbbVie Inc., and may hold AbbVie Inc. stock and/or stock options. Arjun Tarakad declarations of interest: none. Eric Freire-Alvarez has received advisory, consulting, and lectures fees from AbbVie Inc., Teva, Bial, Zambon, Esteve, UCB, and Neuraxpharm; and is an investigator on studies funded by AbbVie Inc., Neuroderm, Cerevel, Roche, Anavex, Bial, Zambon, Impax, and Irlab. Enrique Urrea-Mendoza has received advisory/consulting fees from: AbbVie Inc., Defeat MSA USA, and Medtronic. Filip Bergquist has received advisory and lecture fees from AbbVie Inc., GKC, and Britannia; and research support in kind from GKC. He is a board member of Arvid Carlsson Research AB and receives salary from the University of Gothenburg and Sahlgrenska University Hospital. Jason Aldred is a member of the faculty of the University of Washington and Washington State University. He is a study investigator and has received honorarium from AbbVie Inc., Allergan (now AbbVie Inc.), Teva, US WorldMeds, Medtronic, and Abbott. He is an investigator in studies sponsored by AbbVie Inc., Biogen, Acadia, Northwestern University, Neuroderm, Massachusetts General Hospital, and AstraZeneca. He is also a scientific advisor for AbbVie Inc. He has a clinical practice through Selkirk Neurology. Jia Jia is an employee of AbbVie Inc., and may hold AbbVie Inc. stock and/or stock options. Jorge Zamudio is an employee of AbbVie Inc., and may hold AbbVie Inc. stock and/or stock options. Manon Bouchard has received honoraria for consultancy, lectures, and advisory boards from AbbVie Inc., Allergan (now AbbVie Inc.), Merz, Ipsen, Lilly, Novartis, Paladin, Sunovion, and UCB. She is an investigator for AbbVie Inc., ES-therapeutics, Biohaven, and Pfizer. Maurizio F. Facheris is an employee of AbbVie Inc., and may hold AbbVie Inc. stock and/or stock options. Michael J. Soileau has received advisory/consulting fees from: AbbVie Inc., Abbott, Mertz Therapeutics, Medtronic, and Supernus. He has received research support from: AbbVie Inc., Cerevel Therapeutics, CND Lifesciences, Praxis Precision Medicine, and Teva. He has served on the speaking bureau for: AbbVie Inc., Amneal Pharmaceuticals, Kyowa Kirin, and Neurocrine Pharmaceuticals. Martha P. Arroyo is a study investigator with Leo Pharma and Allakos, and has received honoraria and consultant fees from AbbVie Inc. and BMS. She has a clinical practice through Lakeside Dermatology. Nahome Fisseha is an employee of AbbVie Inc., and may hold AbbVie Inc. stock and/or stock options. Pavnit Kukreja is an employee of AbbVie Inc., and may hold AbbVie Inc. stock and/or stock options. Robert A. Hauser serves on a scientific advisory board for Inhibikase and Stoparkinson. He has received consulting fees from AbbVie Inc., Amneal Pharmaceuticals, Avanex, Biogen, BlueRock Therapeutics, Forsee Pharmaceuticals, Global Kinetics, Inhibikase, Jazz Pharmaceuticals, Kyowa Kirin, MDCE Suzhou, MedRhythms, Merck, Merz, Neurocrine, Neuroderm, Ovid Therapeutics, PD Neurotechnology, Pharma Two B, Regenxbio, Revance, Sage Therapeutics, Scion NeuroStim, Stoparkinson, Sunovion, Supernus Pharmaceuticals, Tolmar, Tremor Research Group, Tris Pharma, UCB, and Vivifi Biotech. He has received speaking fees from Acorda, Amneal Pharmaceuticals, Cerevel, Inhibikase, Kyowa Kirin, Neurocrine Biosciences, Sunovion, and Supernus. His University has received research support from AbbVie Inc., Aeon Biopharma, Annovis Bio Inc., Artizan Biosciences, Biogen MA, Bukwang Pharmaceutical Co. Ltd., Cavion Inc., Cerevance Inc., Cerevel Therapeutics, Cynapsus Therapeutics, Enterin Inc., Genetech, Global Kinetics Corporation, Hoffman-La Roche Inc., Impax Laboratories, Inhibikase Therapeutics, Integrative Research Laboratories Sweden, Lundbeck Inc., Michael J. Fox Foundation for Parkinson’s Research, National Parkinson’s Foundation, Neuraly Inc., Neurocrine Biosciences, Neuroderm, Parkinson’s & Movement Disorder Alliance, Pharma Two B Ltd., Revance Therapeutics, Sage Therapeutics, Sanofi Pharmaceuticals, Scion NeuroStim, SunPharma, and UCB BioPharma. He holds stock options in Axial Therapeutics, Enterin, and Inhibikase as well as holds stock in Revance Therapeutics. He has received intellectual property interests from a Parkinson’s Disease Diary through his University. He acknowledges a Center of Excellence grant from the Parkinson Foundation. Rajesh Pahwa serves as a consultant for Abbott, AbbVie Inc., ACADIA, Acorda, Adamas, Amneal, CalaHealth, Global Kinetics, Impel, Neuropharma, Kyowa, Lundbeck, Mitsubishi, Neurocrine, Orbis Bioscience, PhotoPharmics, Prilenia, Sunovion, Teva Neuroscience, and US WorldMeds. He receives research support from Abbott, AbbVie Inc., Addex, Biogen, Biohaven, Boston Scientific, EIP, Global Kinetics, Impax, Intec, Lilly, Neuroderm, Neuraly, Parkinson’s Foundation, Pharma 2B, Prelinia, Roche, SIS, Sun Pharma, Sunovion, Theranexus, Theravance, US WorldMeds, and Voyager. He is also an investigator for AbbVie Inc. Sarah Bray has received advisory fees from AbbVie Inc., receives a salary from NSW Health, and is a Nurse Coordinator on studies funded by AbbVie Inc. Sara Dhanani received advisory honoraria from Amneal and AbbVie Inc., and is an investigator on studies funded by AbbVie Inc. Saritha Talapala is an employee of AbbVie Inc., and may hold AbbVie Inc. stock and/or stock options. Victor S. C. Fung receives a salary from NSW Health; has received unrestricted research grants from the Michael J. Fox Foundation, AbbVie Inc., and Merz; and receives royalties from Health Press Ltd. and Taylor and Francis Group LLC., (© 2024 AbbVie Inc.)

This article discusses the practicalities of syringe drivers (subcutaneous continuous infusion pumps) for symptom control in patients requiring palliative or end-of-life care, which may form part of an advance care plan. It includes a discussion of palliative and end-of-life care, advance care planning, and when a syringe driver might be beneficial for the patient. It also provides step-by-step clinical guidance on setting up a syringe driver. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine effects of subcutaneous (s.c.) infusions of Ca at calving day on serum concentrations of Ca, P, Mg, β-hydroxybutyrate (BHB), glucose, body condition score (BCS), milk yield, and health in fresh cows receiving a dietary cation-anion difference diet during the dry period. Three hundred seventy-five fresh Holstein cows were blocked based on parity (143 cows in first parity, 108 cows in second parity, and 124 cows in third or greater parity) and randomly assigned to 1 of 4 experimental treatments immediately after calving. Treatments were control group without infusion (control; n = 190); 1 s.c. infusion of 250 mL of 40% Ca borogluconate (1SC250; n = 72) at calving; 1 s.c. infusion of 500 mL of 40% Ca borogluconate (1SC500; n = 63) at calving; 2 s.c. infusions of 250 mL of 40% Ca borogluconate, one immediately after calving and the second 12 to 18 h after first infusion (2SC250; n = 50). Blood samples were collected immediately after parturition and at 1, 2, 4, and 7 d in milk (DIM) for Ca, P, and Mg determination. Milk production, milk composition, and somatic cell count were recorded monthly up to 90 DIM. The evaluation of BCS was performed at calving and at 38 DIM. A subset of 9 cows per treatment group was randomly chosen to measure serum concentration of glucose and BHB at 2, 4, and 7 DIM. Total serum Ca in 1SC250 (8.95 mg/dL), 1SC500 (9.27 mg/dL), and 2SC250 (9.07 mg/dL) was greater during the first week postpartum compared with control (8.45 mg/dL). Serum concentrations of P, Mg, BHB, glucose, and milk yield were not affected by treatments. The dry matter intake during the first 24 h after calving was higher for treatments 1SC250 (13.5 kg), 1SC500 (15.0 kg), and 2SC250 (15.6 kg) relative to control (12.5 kg). Milk somatic cell counts were lower for 1SC500 (90.5 cells/mL) and 2SC250 (82.2 cells/mL) than control (132.8 cells/mL). Risk ratio was >1 for development of metritis, and clinical and subclinical endometritis in control cows relative to 2SC250 cows, which indicates a higher risk of developing disease for control cows (2.03, 1.7, and 1.8 times, respectively). These results suggest that prophylactic s.c. infusions of Ca at calving can improve postpartum Ca status in Holstein cows and intake at 1 DIM. Given the reduction of metritis, clinical and subclinical endometritis, and subclinical hypocalcemia with treatment, the effect of s.c. Ca supplementation on immune status warrants further investigation. [ABSTRACT FROM AUTHOR]

Background: Subcutaneous treprostinil has dose-dependent beneficial effects in patients with severe pulmonary arterial hypertension, but adverse effects like infusion site pain can lead to treatment discontinuation. Objectives: The objective of this study was to evaluate safety, tolerability and clinical effects of a rapid up-titration dosing regimen of subcutaneous treprostinil using proactive infusion site pain management. Methods: Effects of rapid up-titration dosing regimen on tolerability and clinical parameters were evaluated in this 16-week, open-label multi-centre study. Results: Thirty-nine patients with idiopathic or heritable pulmonary arterial hypertension on stable treatment with oral pulmonary arterial hypertension-approved drugs (90% on dual combination therapy) were included. Patients achieved a median treprostinil dosage of 35.7 ng/kg/min after 16 weeks. A good overall safety profile was demonstrated with 3 patients (8%) withdrawing due to infusion site pain, which occurred in 97% of patients. After 16 weeks, median 6-min walking distance, cardiac index, pulmonary vascular resistance, and tricuspid annular plane systolic excursion improved. Conclusions: Rapid up-titration of subcutaneous treprostinil was well tolerated, achieving a clinically effective dose associated with improvement of exercise capacity and haemodynamics after 16 weeks. A rapid dose titration regimen and proactive infusion site pain management may improve the handling of this therapy and contribute to better treatment outcome. [ABSTRACT FROM AUTHOR]

A novel, self-administration drug delivery system for subcutaneous infusion was developed and evaluated. The device includes two main components: an osmotic tablet controlled gas actuator and a syringe catheter system. The sodium carbonate in the osmotic pump tablet will release into the surround citric acid solution and produce CO2gas, which will drive the drug solution into subcutaneous tissue. The key formulation factors of the osmotic tablet that would influence the infusion profiles of the device were investigated by single factor exploration. The formulation was optimized via a response surface methodology. With an 18 ± 4 min of lag time, the delivery system was able to infuse at an approximate zero-order up to 5.90 ± 0.37 h with a precision of 9.0% RSD (n = 6). A linear correlation was found for the infusion profile and the fitting equation wasY = 0.014X − 0.004 (r = 0.998). A temperature change of 4 °C was found to modify the flow rate by about 12.0%.In vivoresults demonstrated that the present subcutaneous infusion device was similar to the commercial infusion pump, and it could bring a long and constant ampicillin plasma level with minimized fluctuations. [ABSTRACT FROM AUTHOR]

We report a case of delayed respiratory depression due to accidental subcutaneous opioid infusion. A healthy 33-year-old woman underwent orthopedic surgery under general anesthesia. Before the end of the operation, it was noticed that a part of the opioid infusion had been administered subcutaneously. About 15 min after tracheal extubation, the patient developed respiratory depression and loss of consciousness. The patient recovered with the use of jaw lift together with bag-valve-mask ventilation. We believe that accidental subcutaneous opioid accumulation may have caused the respiratory depression. [ABSTRACT FROM AUTHOR]

It is difficult to manage the symptoms of patients who are dying of end-stage heart failure (HF). Opioids are sometimes required to relieve their symptoms in addition to oxygen therapy and medical management. Oxycodone is a μ receptor agonist that is known to be a safer opioid than morphine in patients with chronic kidney disease (CKD) because its metabolites have weak pharmacological activity. We treated a 99-year-old woman who had end-stage HF (secondary to severe aortic stenosis) and CKD. It was also difficult to maintain an intravenous line because of severe edema. We administered oxycodone subcutaneously and successfully alleviated her severe symptoms without severe adverse effects of opioids until a few days before her death. We report this case and discuss the possibility of using subcutaneous oxycodone as a new palliative care strategy in patients with end-stage HF. < Learning objective: We report the management of chest symptoms of an elderly patient with end-stage heart failure (HF) due to severe aortic stenosis by subcutaneous infusion of oxycodone. This method has a possibility to alleviate chest symptoms of end-stage HF with less severe adverse effects until a few days before death than morphine, and may be useful to manage the symptoms even in patients with severe edema. Further investigation will be required to compare subcutaneous oxycodone with intravenous morphine.> [ABSTRACT FROM AUTHOR]

Syringe drivers are widely used in palliative care, and this article reviews the challenges and outstanding questions associated with their use. Misperceptions among the lay public and some health professionals can be addressed by sensitive communication with patients and families and clear thinking in clinical teams concerning the drugs and doses used, particularly in non-malignant disease. Good levels of knowledge concerning syringe driver use has been found among GPs and community nurses, although this is not the case in some nursing home teams. The advantages of newer devices, safety and efficacy of drug combinations, selection of diluent, and management of site reactions are discussed. [ABSTRACT FROM AUTHOR]

Subcutaneous administration of medications and/or fluids can play a crucial part in supporting patients at home and thereby avoiding the need for hospitalisation. It is an area of patient care that has received little attention compared with other types of parenteral therapies. However, it is an effective and safe route for continuous administration for individuals requiring palliative care. Technological advancements have led to improved subcutaneous infusion devices, such as fine-gauge cannulae with integral sharps protection, as well as integral hypoallergenic dressings. These design features not only help to increase patient comfort but also minimise the potential for needlestick injuries, as well as providing the health professional with one sterile package containing all of the components needed to establish subcutaneous infusion. However, technological developments alone are insufficient to improve patient outcomes. Knowledge of the individual patient, together with their diagnosis and intended treatment, will influence the choice of subcutaneous infusion device, with the overall aim of minimising the potential for complications and improving comfort. This paper provides an overview of subcutaneous infusion, including the importance of patient assessment and the education and training needs of health professionals, and then focuses on one specific subcutaneous infusion device: the neria soft 90 infusion set. [ABSTRACT FROM AUTHOR]

Objectives: To assess the impact of electronically prescribed mixed-drug infusions on the prevalence and types of prescription errors and staff time.Design, Setting and Participants: Before-and-after study on acute medical wards of a large UK teaching hospital, utilising patient and staff data from the assessed wards.Intervention: Electronically-generated mixed-drug infusions.Main Outcome Measures: (1) Rate of prescription errors (divided into errors of commission and omission); (2) time taken to process patient discharge prescriptions containing a mixed-drug infusion; and (3) time between prescription and administration of mixed-drug infusions.Results: 100 errors of omission were detected pre-intervention, whilst none were detected post intervention. 6 errors of commission were identified at baseline, whilst 2 were highlighted post intervention (p = 0.149). 14 physicochemically incompatible infusions were prescribed at baseline, post-intervention all infusions were compatible (p < 0.01). Time spent processing discharge prescriptions fell from 60 min (SME±1.7) to 26 min (SME± 2.7; p < 0.01). The median time from prescription to administration reduced from 120 min (95 % CI 106-150) to 65 min (95 % CI 43-85; p < 0.01).Conclusions: The intervention eliminated errors of omission and facilitated the prescribing of compatible multicomponent infusions. Electronically prescribed mixed-drug infusions also reduced both the time taken to complete discharge prescriptions and the time taken to commence such infusions. [ABSTRACT FROM AUTHOR]

Idiopathic hypersomnia (IH) is a rare sleep disorder, recently hypothesized to be related to the production of a molecule that facilitates the binding of gamma-aminobutyric acid (GABA) to the GABA receptor. This paper reports on the treatment of a patient with IH who was treated with a 96-hour continuous low dose (4 mg/day) infusion of a benzodiazepine antagonist, flumazenil, followed by a slow-release flumazenil implant. The use of flumazenil mitigated the patient’s IH symptoms including excessive daytime sleepiness, sleep drunkenness and self-reported cognitive problems. The case both provides a possible treatment and system for short (subcutaneous (SC) administration) and longer term (implant) flumazenil delivery. Current data supports the need for further research into the use of flumazenil for the treatment of IH and to develop long term flumazenil delivery systems. [ABSTRACT FROM PUBLISHER]

Continuous subcutaneous apomorphine infusion therapy (CSAI) has proved to be effective in advanced Parkinson's Disease patients with motor fluctuations not controlled by oral or transdermal medication. In this clinical setting it competes directly with intrajejunal levodopa and deep brain stimulation (DBS), however randomised controlled comparative studies are lacking. The advantages of CSAI is that it is the least invasive of these three therapeutic options, is reversible, practical to use and has shown significant efficacy for the management of both peak-effect dyskinesias and off-period nonmotor-symptoms. Contraindications to the use of CSAI are severe dementia or neuropsychiatric symptoms and severe biphasic dyskinesias, however unlike DBS, advanced age is not a contraindication. This review summarises the evidence regarding efficacy, safety and tolerability of CSAI, provides guidance on the selection of suitable patients and gives practical instructions on how to initiate CSAI and manage possible adverse events. [ABSTRACT FROM AUTHOR]

Since the first description of subcutaneous protein C concentrate as treatment for severe protein C deficiency in 1996, further cases have been reported but there is no uniform approach to this form of treatment. In order to assess the safety and effectiveness of subcutaneous protein C concentrate and suggest recommendations for future use, patients who had received subcutaneous protein C concentrate were identified from the literature, by contacting the manufacturers and by personal communication. Treatment details were available from 14 cases. Apart from one case where the infusion interval was inadvertently increased, no thrombotic events occurred even when doses were subsequently reduced. Initially, a trough protein C level of >0·25 iu/ml should be aimed for. Subsequently, a smaller dose of subcutaneous protein C concentrate, especially if taken with an oral anticoagulant, may be protective maintenance treatment. The treatment was well tolerated with few side effects. Subcutaneous protein C concentrate on its own or combined with an oral anticoagulant appears to be safe and effective as maintenance treatment of severe protein C deficiency. A major advantage is the avoidance of central venous access devices. The incidence of neurodevelopmental handicap was high with blindness affecting the majority of patients. [ABSTRACT FROM AUTHOR]

An economical, convenient portable drug delivery system combining osmotic pump with subcutaneous infusion was developed, which was composed of three primary components: water chamber, osmotic pump chamber and support base. Ceftriaxone sodium (CRO) was selected as the model drug and osmotic pump tablets were prepared. The influence of osmotic agents on drug release profiles was evaluated. As the adjustment made by the osmotic agents was limited, the compositions of semipermeable membrane were investigated to determine significant associations of factors based on orthogonal design. The in vitro release profiles of the optimum formulation achieved to the predetermined value (15 ± 3 min for the initial release time Ti and 5.75 ± 0.25 h for the extent release time Te). The pharmacokinetic profiles of this drug delivery system were evaluated in Beagle dogs. In vivo results demonstrated that the osmotic pump subcutaneous infusion administration was equivalent to intravenous injection administration in terms of bioavailability. Moreover, constant drug plasma levels with minimized fluctuations could be achieved with this osmotic pump subcutaneous infusion system, compared with intravenous injection. [ABSTRACT FROM AUTHOR]

Subcutaneous infusion of apomorphine is a useful treatment for motor and nonmotor complications in Parkinson's disease patients and improves the patient's quality of life. An adequate selection of suitable candidates is crucial for obtaining the best results with this therapy. Parkinsonian patients with severe biphasic dyskinesias, demented or having experienced serious neuropsychiatric side effects with other dopamine agonists should not be offered this treatment. The therapeutic effect of continuous apomorphine infusion is reviewed and practical recommendations on its use are provided. [ABSTRACT FROM AUTHOR]

Patients with diabetes mellitus type 1 depend on exogenous insulin to keep their blood glucose concentrations within the desired range. Subcutaneous bihormonal artificial pancreas devices that can measure glucose concentrations continuously and autonomously calculate and deliver insulin and glucagon infusions is a promising new treatment option for these patients. The slow absorption rate of insulin from subcutaneous tissue is perhaps the most important factor preventing the development of a fully automated artificial pancreas using subcutaneous insulin delivery. Subcutaneous insulin absorption is influenced by several factors, among which local subcutaneous blood flow is one of the most prominent. We have discovered that micro-doses of glucagon may cause a substantial increase in local subcutaneous blood flow. This paper discusses how the local vasodilative effects of micro-doses of glucagon might be utilised to improve the performance of subcutaneous bihormonal artificial pancreas devices. We map out the early stages of our hypothesis as a disruptive novel approach, where we propose to use glucagon as a vasodilator to accelerate the absorption of meal boluses of insulin, besides using it conventionally to treat hypoglycaemia., Competing Interests: The authors SMC and SCC are among the inventors of a pending patent application on the use of micro-doses of glucagon to enhance SC CGM performance and SC insulin absorption. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Teigen, Riaz, Åm, Christiansen and Carlsen.)

The article discusses a study which examines the correlation between drugs administered subcutaneously via a syringe driver and the incidence of syringe driver site reactions in palliative care. A data collection form was used, when a subcutaneous infusion via a syringe driver was performed. Statistical data analysis showed incidence of syringe driver site reaction. It suggests use of Teflon cannula needle and recommends change of syringe needle driver every 6 days, if drugs are unknown.

The year 1952 marked the first use of subcutaneous immunoglobulin therapy to treat primary immunodeficiency disease. Subsequently, intramuscular and then intravenous administration became the norm in the United States and most of Europe. Intravenous immunoglobulin therapy, however, can be burdensome and often causes systemic side effects. To overcome obstacles presented by the intravenous route of administration, subcutaneous preparations were developed. To further enhance patient satisfaction, adherence, and quality of life, enzyme-enhanced subcutaneous immunoglobulin administration using hyaluronidase, an enzyme spreading agent, was studied. The dose and flow rate of traditional subcutaneous immunoglobulin infusion is limited by the inhibition of bulk fluid flow by the extracellular matrix. Recombinant human hyaluronidase, administered with or immediately prior to infusate, increases the absorption and dispersion of infused fluids and drugs. Results from a phase III clinical trial indicate that subcutaneous immunoglobulin infusion, facilitated by recombinant human hyaluronidase, is well tolerated, and delivers infusion volumes at treatment intervals and rates equivalent to intravenous administration. This review surveys the state of the art of immunoglobulin replacement therapy. [ABSTRACT FROM AUTHOR]