Open-source, 3D-printed Peristaltic Pumps for Small Volume Point-of-Care Liquid Handling.

Microfluidic technologies are frequently employed as point-of-care diagnostic tools for improving time-to-diagnosis and improving patient outcomes in clinical settings. These microfluidic devices often are designed to operate with peripheral equipment for liquid handling that increases the cost and complexity of these systems and reduces their potential for widespread adoption in low resource healthcare applications. Here, we present a low-cost (~$120), open-source peristaltic pump constructed with a combination of three dimensional (3D)-printed parts and common hardware, which is amenable to deployment with microfluidic devices for point-of-care diagnostics. This pump accepts commonly available silicone rubber tubing in a range of sizes from 1.5 to 3 mm, and is capable of producing flow rates up to 1.6 mL min-1. This device is programmed with an Arduino microcontroller, allowing for custom flow profiles to fit a wide range of low volume liquid handling applications including precision liquid aliquoting, flow control within microfluidics, and generation of physiologically relevant forces for studying cellular mechanobiology within microfluidic systems.

Efficiency and Safety of Aftercare With Intrathecal Baclofen on Location.

OBJECTIVES: Patients with intractable spasticity treated with intrathecal baclofen (ITB) need regular evaluation and aftercare in an outpatient clinic or pain clinic setting. Logistically, this can be challenging. A solution could be to perform treatment at the patient's home setting. In the Netherlands, a project of the Dutch Healthcare Authority was initiated to deliver ambulatory ITB-related services via a home-based Ambulant Care Clinic. This aftercare is performed by nurse practitioners (NP) with support from a medical specialist. The scope of the study was to investigate the efficiency and safety of ITB-care for patients with severe disabling spasticity in their home setting. MATERIALS AND METHODS: A retrospective analysis of prospectively collected data. Patients with congenital or acquired spasticity were treated with ITB (1st April 2011 to January 1st 2016) using an implanted programmable pump system were referred to the home-based Ambulant Care Clinic by various neuromodulation centers in the Netherlands. All study parameters were a part of the standard intake and follow-up documentation. RESULTS: Of the 900 patients treated with ITB in the Netherlands, 239 were referred to the home-based Ambulant Care Clinic and included in this study. Mean age was 45.5 (range 7-82) years; 52% lived at home; the average satisfaction score was 9 (scale 0-10); and 0.29% had (serious) adverse events (60% of clinical manifestations were prevented by remote double-check control). Certifications for patient safety and quality standards were obtained. CONCLUSIONS: The concept of ITB aftercare on location demonstrated efficacy and safety in the described setting. For troubleshooting, close collaboration with a neuromodulation center is necessary and can be arranged in chain-based care.

Intrathecal Baclofen Therapy in Patients With Multiple Sclerosis: Improved Outcomes and Reduced Costs Through Identification of Catheter Malfunction.

INTRODUCTION: Two patients previously implanted with intrathecal Baclofen (ITB) pumps for management of intractable spasticity due to multiple sclerosis (MS) were referred to our center for ongoing management of their spasticity. Initial evaluation of these patients revealed high levels of spasticity in the presence of ITB doses 10 times the average daily dose of our other MS patients. CLINICAL FACTS: High doses of ITB required frequent clinical visits and result in high drug and procedure costs. Both patients' daily doses were greater than 1000 mcg/day resulting in clinical visits every 1-2 months with drug and procedure costs ranging from 16 to 23 thousand dollars annually based on Medicare national average pricing for physician's office. Of the 59 MS patients receiving ITB therapy at our institution, the mean, median, and mode daily doses for ITB are 184, 115, and 159 mcg/day, respectively. The high ITB doses in these patients and poor spasticity control raised suspicion for pump/catheter malfunction and prompted immediate troubleshooting. FINDINGS: One patient's catheter was found to be disconnected from the pump and the other's catheter tip was outside the intrathecal space. In both cases, the patients were not receiving the therapy. After pump/catheter replacement, both patients received excellent clinical benefits from ITB at significantly lower daily doses. This reduction in dose resulted in decreased frequency of medication refills (twice annually) which resulted in decreased cost of care (12-19 thousand dollars savings annually per patient). DISCUSSION: These cases illustrate the need for early ITB pump troubleshooting to identify catheter problems, improve efficacy, and avoid unnecessary healthcare costs.

Accuracy and Precision of the SynchroMed II Pump.

OBJECTIVE: The objective of this study was to evaluate the accuracy and precision of SynchroMed II programmable infusion pumps for delivery of intrathecal baclofen to treat severe spasticity. DESIGN: Retrospective chart review study. SETTING: Urban academic rehabilitation clinic. PATIENTS (OR PARTICIPANTS): Patients with spasticity treated with intrathecal baclofen. METHODS OR INTERVENTIONS (OR ASSESSMENT OF RISK FACTORS): A retrospective chart review of 149 patients inclusive of 755 individual patient encounters more than a 2.5-year span for baclofen pump refills was performed. MAIN OUTCOME MEASUREMENTS: Charts were reviewed to obtain data on the concentration and dose of intrathecal baclofen, aspirated and residual volumes, age of the pump, and reservoir volume of the pump. Flow rate (mL/day) was calculated for each chronological visit. Flow rates from clinical data were used to calculate the accuracy and precision based on the manufacturer's specifications for both the 20 mL and 40 mL pumps. RESULTS: The infused volume accuracy and precision of both the 20 mL pumps and 40 mL pumps remained within manufacturer's specifications while delivering drug at a rate slightly lower than predicted. There were no cases of pump over-infusion. There is a statistically significant decrease in flow rate accuracy over the lifespan of the pump. CONCLUSIONS: SynchroMed II pumps infuse at slightly less than their predicted rate while remaining within the manufacturer's specifications. No pump over-infusions were noted. Pump flow rate declines over time. Further study is warranted to assess the impact of this flow rate decrease on patient treatment and safety.

Perioperative and Periprocedural Care of Patients With Intrathecal Pump Therapy.

INTRODUCTION: There are an ever-increasing number of patients who have implanted devices for targeted delivery of drug therapy to the intrathecal space for the management of spasticity or chronic pain. This leads to a growing number of people with implanted pumps presenting for procedures and surgeries, yet there is a paucity of consolidated information available to describe the appropriate precautions and patient management during this period. METHODS: This was a systematic review to provide a summary of existing literature on intrathecal drug delivery system (IDDS) management in the perioperative and procedural period, and to highlight additional areas that require further research. Topics addressed include the time surrounding magnetic resonance imaging, defibrillation, radiation therapy, high output ultrasound, lithotripsy, ablation, diathermy, electroconvulsive therapy, and the perioperative period, all of which have their own specific considerations. RESULTS: A total of 42 articles met criteria to be included in this review. Inclusion criteria were English language, and that the article was primarily focused on the perioperative or periprocedural management of IDDSs. Exclusion criteria included commentaries, surveys, published abstracts, or articles that did not discuss the perioperative or periprocedural care of IDDS. CONCLUSION: Our article outlined perioperative considerations when dealing with a patient with intrathecal pump undergoing surgical or imaging modality.

A Novel Approach to Avoid Baclofen Withdrawal When Faced With Infected Baclofen Pumps.

BACKGROUND: Intrathecal (IT) Baclofen is beneficial for spasticity, but if pumps become infected necessitating removal, baclofen withdrawal is difficult to manage and life-threatening. Furthermore there is no consistency between dosing and severity of withdrawal. Case reports detail full baclofen withdrawal at dosages of 260 µg/day. OBJECTIVE: To demonstrate that in patients on stable IT baclofen for prolonged periods, externalizing a patient's original IT pump is a safe, effective way to wean IT doses. METHODS: Here, we describe a technique of continuing IT baclofen when urgent pump removal is needed. Specifically, we remove the infected pump. Then using a new or existing lumbar drain based on extent of infection, we reconnect the pump after cleaning with betadine and administer therapy externally during IT weaning. RESULTS: Hundred forty seven baclofen pumps were implanted or replaced within four years. Infections occurred in seven patients. We utilized this technique in five of seven patients. Mean IT dose at time of explant was 400.5 ± 285.3 µg/day. We titrated the dose by 20-50% per day based on clinical response over a mean of 6.2 ± 1.3 days. The catheter was removed at bedside once weaning was complete. No patients had any signs of withdrawal, excluding minimal spasticity increases while optimizing oral treatment. CONCLUSION: Here, we show preliminary evidence that an externalized IT pump is an effective means of weaning IT baclofen when infection of the pump occurs. This treatment strategy warrants further investigation, but appears to be a safe and effective. CONFLICT OF INTEREST: Dr. Pilitsis is a consultant for Medtronic, Boston Scientific, Nevro, Jazz Pharmaceuticals, Neurobridge Therapeutics, and Abbott and receives grant support from Medtronic, Boston Scientific, Abbott, Nevro, Jazz Pharmaceuticals, GE Global Research and NIH 1R01CA166379. She is medical advisor for Centauri and Karuna and has stock equity. Dr. Sukul receives consultant fees from Medtronic. Julia Prusik receives grant support from Jazz Pharmaceuticals.

Refill Procedures of Intrathecal Drug Delivery Systems With a Recessed Fill Port on the Pump Surface: A Prospective Comparison Study of Ultrasound-Guided vs. Blind Refill Technique.

OBJECTIVES: Structural differences of implantable drug delivery systems (IDDSs) might have an impact on the efficiency of needle access to the reservoir fill port (RFP). The aim of this study was to assess the efficiency of RFP needle access with an ultrasound (US)-guided vs. a blind refill technique in IDDSs with a Recessed RFP (Recessed-RFP-IDDS). MATERIALS AND METHODS: The primary outcome was the number of attempts needed to enter the RFP with a needle comparing the US-guided technique vs. the blind refill technique. The time to enter the RFP with the needle was a secondary outcome. We compared the amount of attempts between both techniques with the non-parametric Wilcoxon rank sum test. RESULTS: Fourteen adult patients underwent a total of 75 refills of their Recessed-RFP-IDDS during a period of 24 months. The median number of attempts to enter the RFP did not differ significantly between the US-guided technique and the blind refill technique (2.0 (IQR: 1-5) vs. 1.5 (IQR: 1-5.0), p = 0.572). The median time to enter the RFP with the needle did not differ significantly between both techniques (35.0 sec (IQR: 26.0-58.0) vs. 41.0 sec (IQR: 25.5-46.8), p = 0.878). CONCLUSION: The results of this study suggest that there is no difference in the RFP needle access efficiency between the US-guided and the blind refill technique in superficially located Recessed-RFP-IDDSs, if performed by experienced practitioners. However, the study did not address efficiency of the RFP needle access in IDDSs with aberrancy in pump location or refills performed by inexperienced staff.

Infections of Intrathecal Baclofen Delivery Systems and Ventriculoperitoneal Shunting Systems: Clinical Series Discussion.

BACKGROUND/AIMS: The physiological interaction between the intrathecal baclofen (ITB) delivery system and the ventriculoperitoneal (VP) shunting system in a patient who had both systems implanted has not been reported previously. The aim of our report is to evaluate the effect that one system's infection might have on the other. METHODS: Records of children who were followed at our institution between 2004 and 2015 for management of their ITB systems were reviewed. In this group, children who had VP shunts were identified, and those who had any of their ITB or VP systems infected were included. RESULTS: Out of 313 children managed with ITB therapy at our institution, 31 (24%) children had VP shunts. Two patients had infection in both systems, and 3 patients had infection in 1 system. CONCLUSION: This report suggests that if aspiration from both systems showed positive cultures, the treatment would be removal of both systems. If the primarily not infected system does not show positive cultures, it does not need to be removed. Close follow-up is recommended, and any sign of infection or malfunction of the primarily not infected device should be approached with a high level of suspicion.

The Polyanalgesic Consensus Conference (PACC): Recommendations for Intrathecal Drug Delivery: Guidance for Improving Safety and Mitigating Risks.

INTRODUCTION: Intrathecal therapy is an important part of the pain treatment algorithm for chronic disease states. The use of this option is a viable treatment strategy, but it is inherent for pain physicians to understand risk assessment and mitigation. In this manuscript, we explore evidence and mitigating strategies to improve safety with intrathecal therapy. METHODS: A robust literature search was performed covering January 2011 to October 9, 2016, in PubMed, Embase, MEDLINE, Biomed Central, Google Scholar, Current Contents Connect, and International Pharmaceutical Abstracts. The information was cross-referenced and compiled for evidence, analysis, and consensus review, with the intent to offer weighted recommendations and consensus statements on safety for targeted intrathecal therapy delivery. RESULTS: The Polyanalgesic Consensus Conference has made several best practice recommendations to improve care and reduce morbidity and mortality associated with intrathecal therapy through all phases of management. The United States Prevention Service Task Force evidence level and consensus strength assessments are offered for each recommendation. CONCLUSION: Intrathecal therapy is a viable and relatively safe option for the treatment of cancer- and noncancer-related pain. Continued research and expert opinion are required to improve our current pharmacokinetic and pharmacodynamic model of intrathecal drug delivery, as this will undoubtedly improve safety and efficacy.

Solubility and Stability of Baclofen 3 mg/mL Intrathecal Formulation and Its Compatibility With Implantable Programmable Intrathecal Infusion Systems.

BACKGROUND: Commercial baclofen formulations used with infusion pumps are available at therapeutic concentrations of 0.5-2.0 mg/mL. However, patients who receive higher daily doses of baclofen may benefit from products with greater baclofen concentrations since their refill frequency would be reduced (up to a maximum of 180 days). We evaluated baclofen solubility, baclofen 3 mg/mL intrathecal (IT) formulation stability, and chemical and physical compatibility with Medtronic SynchroMed® II and Codman Medstream® programmable IT infusion pumps. METHODS: For solubility evaluations, baclofen powder was dissolved into isotonic saline and tested at 5°C, 25°C, and 40°C. To demonstrate drug product stability, both physical and chemical stability attributes of baclofen 3 mg/mL in prefilled syringes were evaluated over 36 months with storage at 25°C. For a simulated in-use stability (compatibility) study, a 3 mg/mL baclofen IT formulation was placed in SynchroMed II and Codman Medstream pumps at 37ºC for study durations, and evaluated at different flow rates. Pump effluent was collected at various times and analyzed by high-performance liquid chromatography for baclofen content. On completion of the in-use stability study, pumps exposed to baclofen 3 mg/mL were dissected and visually evaluated for signs of deterioration. RESULTS: Baclofen solubility was found to be 3.2 mg/mL at 5°C, 3.6 mg/mL at 25°C, and 3.9 mg/mL at 40°C. During the 36-month stability study of prefilled syringes stored at 25°C, baclofen content remained unchanged and no precipitation was observed. The simulated in-use pump study performed at 37ºC showed that a baclofen 3 mg/mL IT formulation was stable at different flow rates and throughout different expected residence times for both pump models. Components from both pumps exhibited no noticeable deterioration after exposure to the 3 mg/mL formulation. CONCLUSION: Baclofen 3 mg/mL IT formulation was stable during long-term storage at 25°C and remained stable under conditions matching those encountered in clinical practice (37°C).

A Prospective, Randomized, Single-Blinded, Head-to-Head Long-Term Outcome Study, Comparing Intrathecal (IT) Boluses With Continuous Infusion Trialing Techniques Prior to Implantation of Drug Delivery Systems (DDS) for the Treatment of Severe Intractable Chronic Nonmalignant Pain.

OBJECTIVE: The study aims to compare intrathecal (IT) boluses to continuous infusion trialing techniques prior to implantation of drug delivery systems (DDS) for the treatment of severe intractable chronic nonmalignant pain. DESIGN: This is a prospective, randomized, head-to-head long-term outcome study. MATERIALS AND METHODS: Forty patients with comparable patient demographics were randomly assigned to two cohorts. Cohort A trialed with intermittent boluses; Cohort B trialed with continuous infusion. One patient failed trial in each group. Nineteen patients were implanted in each group. Follow-up was for 36 months with intervals at 6, 12, 18, 24, 36 months. The Brief Pain Inventory was used was used for assessment. OUTCOME MEASURES: We used the Brief Pain Inventory to measure pain (worst and average), physical function (walking, normal work, and general activity), behavioral function (mood, sleep, and relations with others), IT dose, and oral opioid use. RESULTS: We observed statistically significant reduction in pain and improvement of function in both cohorts following DDS implantation throughout the observation period. The IT dose remained virtually unchanged throughout as well, with overall limited dose escalation. Oral opioid use was significantly reduced. There was no statistically significant difference in prediction of trial success or long-term outcomes between the two cohorts. CONCLUSION: Low-dose IT opioids via DDS can provide significant and long-lasting reduction in pain, and improvement in function (physical and behavioral) for patients with chronic nonmalignant pain. The two trialing techniques tested, intermittent boluses, and continuous infusion delivered intrathecally showed no clinical significance difference in terms of predicting trial success or long-term outcomes.

Diabetes Device Interoperability for Improved Diabetes Management.

Scientific and technological advancements have led to the increasing availability and use of sophisticated devices for diabetes management, with corresponding improvements in public health. These devices are often capable of sharing data with a few other specific devices but are generally not broadly interoperable; they cannot work together with a wide variety of other devices. As a result of limited interoperability, benefits of modern diabetes devices and potential for development of innovative new diabetes technologies are not being fully realized. Here we discuss diabetes device interoperability in general, then focus on 4 examples that show how diabetes management could benefit from enhanced interoperability: remote monitoring and data sharing, integrating data from multiple devices to better inform diabetes management strategies, device consolidation, and artificial pancreas development.

[Development possibilities of hormone-containing implants for gynecological applications: A review]. / Nogyógyászati célra szánt, hormontartalmú implantátumok fejlesztési lehetoségeinek áttekintése: irodalmi áttekintés.

Implantable gynecological drug delivery devices are applied for contraceptive, hormone replacement purposes and for the treatments of other gynecological diseases, e.g. endometriosis. The review provides a comprehensive overview about the indications, advantages, limitation of application and the applied technologies of hormone-containing implants, as well. The study comprises the relevant patents and the recently published papers.

Simultaneous subcutaneous implantation of two osmotic minipumps connected to a jugular vein catheter in the rat.

Subcutaneous osmotic pump implantation connected to a venous catheter is a well-established method for delivering compounds intravenously for an intermediate duration (approximately two weeks). When prolonged release is desired (approximately four weeks) reduced flow rate is needed with a similar pump volume. With a fixed intra-pump compound concentration, reduced flow rate results in unwanted reduced bioavailability of the compound. Prolonged intravenous delivery would therefore need a pump replacement, resulting in increased discomfort and confounding effects on experimental outcome. To overcome this, we describe a method to double the compound infusion rate for four weeks by implanting two low-flow rate osmotic pumps (2.5 µL/h for 28 days) connected to a jugular vein catheter in a single rat. Rats implanted with a single high-flow rate pump (5 µL/h for 14 days) served as controls. Double pump-implanted rats displayed similar post-operative weight gain and physical activity indicating similar levels of discomfort when compared with single pump-implanted rats. Double pump-implanted rats had an increased risk of pump-related complications (four delivery failures [double pump] versus one delivery failure [single pump]). Our data show that double pump implantation is a feasible alternative to changing pumps or the use of extracorporeal pump systems connected via a long wire to partly restrained animals.

Complications of intrathecal baclofen pumps in children: experience from a tertiary care center.

BACKGROUND/AIMS: Intrathecal baclofen (ITB) therapy is useful in treating spasticity and dystonia but it has many complications, more so in children. The main aim of the study was to look at the complications of ITB pumps in children with the goal of future prevention. METHODS: Charts of all patients ≤21 years with an ITB pump, implanted by a single pediatric neurosurgeon, at a single center, between 1996 and 2011 were reviewed retrospectively. Data regarding an ITB test trial were also recorded. RESULTS: During 1996-2011, 119 children (mean age 13.2 years) underwent ITB pump placement; 84% had spastic quadriplegic cerebral palsy. The gross motor function classification system level was ≥4 for most. The pump was removed in 5 (4.2%) patients due to inefficacy. The mean follow-up was 38 months. Mechanical complications requiring pump and/or catheter revision occurred in 19.3% and infections in an additional 21.8%. Seven patients (6%) had meningitis. No complication was noted after 72 months of initial pump insertion, even after pump reinsertion. CONCLUSION: There is a need for better infection control as well as better pump, catheter and surgical technology to lower the complications of ITB pumps in children.

Polyanalgesic Consensus Conference--2012: recommendations to reduce morbidity and mortality in intrathecal drug delivery in the treatment of chronic pain.

INTRODUCTION: Targeted intrathecal drug infusion to treat moderate to severe chronic pain has become a standard part of treatment algorithms when more conservative options fail. This therapy is well established in the literature, has shown efficacy, and is an important tool for the treatment of both cancer and noncancer pain; however, it has become clear in recent years that intrathecal drug delivery is associated with risks for serious morbidity and mortality. METHODS: The Polyanalgesic Consensus Conference is a meeting of experienced implanting physicians who strive to improve care in those receiving implantable devices. Employing data generated through an extensive literature search combined with clinical experience, this work group formulated recommendations regarding awareness, education, and mitigation of the morbidity and mortality associated with intrathecal therapy to establish best practices for targeted intrathecal drug delivery systems. RESULTS: Best practices for improved patient care and outcomes with targeted intrathecal infusion are recommended to minimize the risk of morbidity and mortality. Areas of focus include respiratory depression, infection, granuloma, device-related complications, endocrinopathies, and human error. Specific guidance is given with each of these issues and the general use of the therapy. CONCLUSIONS: Targeted intrathecal drug delivery systems are associated with risks for morbidity and mortality that can be devastating. The panel has given guidance to treating physicians and healthcare providers to reduce the incidence of these problems and to improve outcomes when problems occur.

Neuromodulation using intrathecal baclofen therapy for spasticity and dystonia.

Intrathecal baclofen (ITB) therapy is a treatment for intractable spasticity due to a variety of causes. Continuous intrathecal administration of baclofen, an agonist of the inhibitory neurotransmitter γ-aminobutyric acid, inhibits excitation of motor neurons at the spinal level and thus suppresses spasticity. This therapy was introduced clinically in the Europe and the United States in the 1990s, and was finally approved by the Japanese Ministry of Health, Labour and Welfare in Japan in 2005. Clinical use has been permitted since 2006, and reports of therapeutic efficacy are now appearing in Japan. ITB therapy is a non-destructive treatment that enables administration of baclofen from an implantable pump under the control of a programmer, and represents an outstanding treatment method offering both reversibility and adjustability. Indications for ITB therapy have been expanding in recent years to include not only spasticity, but also various causes dystonia. And ITB therapy can greatly improve activities of daily living and quality of life, and this treatment is attracting attention as a neuromodulatory therapy that also affects metabolic and respiratory functions and even state of consciousness. We here report the surgical methods and therapeutic outcomes for 22 patients who underwent ITB therapy for spastic and dystonic patients in our hospital, together with an investigation of the effects on metabolic and respiratory functions.

Polyanalgesic Consensus Conference--2012: consensus on diagnosis, detection, and treatment of catheter-tip granulomas (inflammatory masses).

INTRODUCTION: Continuous intrathecal infusion of drugs to treat chronic pain and spasticity has become a standard part of the algorithm of care. The use of opioids has been associated with noninfectious inflammatory masses at the tip of the intrathecal catheter, which can result in neurologic complications. METHODS: The Polyanalgesic Consensus Conference is a meeting of a group of well-published and experienced practitioners; the purpose of the meeting is to update the standard of care for intrathecal therapies to reflect current knowledge gleaned from literature and clinical experience. An exhaustive literature search was performed, and information from this search was provided to panel members. Analysis of the published literature was coupled with the clinical experience of panel participants to form recommendations regarding intrathecal inflammatory masses or granulomas. RESULTS: The panel has made recommendations for the prevention, diagnosis, and management of intrathecal granulomas. CONCLUSION: The use of chronic infusions of intrathecal opioids is associated with the formation of inflammatory masses at the intrathecal catheter tip in a small minority of treated patients. Nonetheless, the appearance of these space-occupying lesions can lead to devastating neurologic sequelae. The prevention, early detection, and successful treatment of intraspinal granulomas are important considerations when offering intrathecal drug therapy to patients with chronic intractable pain.