Safety, Tolerability, and Pharmacokinetics of High-Volume Subcutaneous Crenezumab, With and Without Recombinant Human Hyaluronidase in Healthy Volunteers.

Compared with intravenous formulations, subcutaneous (s.c.) formulations of therapeutic monoclonal antibodies may provide increased patient access and more convenient administration options, although historically high-volume s.c. administration (> 10-15 mL) has been challenging. We report results from two phase I studies in healthy participants (GP29523 and GP40201) that evaluated s.c. crenezumab, an anti-Aß monoclonal antibody in development for individuals at risk for autosomal-dominant Alzheimer's disease. GP29523 assessed safety, tolerability, and pharmacokinetics (PK) in 68 participants (aged 50-80 years) who received single ascending doses (600-7,200 mg) of crenezumab or placebo (4-40 mL). GP40201 assessed safety, tolerability, and PK in 72 participants (aged 18-80 years) who received different combinations of dose (1,700-6,800 mg), infusion volume (10-40 mL), and flow rate (2-4 mL/minute), with/without recombinant human hyaluronidase (rHuPH20). There were no serious or dose-limiting adverse events in either study. There were no meaningful differences in pain scores among reference placebo (4 mL), test placebo (4-40 mL), or crenezumab (600-7,200 mg) in GP29523, or across treatments with varying infusion volume, flow rate, dose, or rHuPH20 co-administration or concentration in GP40201. Transient erythema was the most common infusion site reaction in both studies. In GP40201 at volumes of ≥ 20 mL, rHuPH20 co-administration appeared to reduce infusion site swelling incidence, but, in some cases, was associated with larger areas of infusion site erythema. Crenezumab exhibited approximately dose-proportional PK, and s.c. bioavailability was 66% and independent of dose or rHuPH20 co-administration. High-dose, high-concentration, high-volume s.c. crenezumab formulated with/without rHuPH20 was well-tolerated in healthy participants, with an acceptable safety profile.

Continuous subcutaneous infusion for pain control in dying patients: experiences from a tertiary palliative care center.

BACKGROUND: Continuous subcutaneous infusion (CSCI) via ambulatory infusion pump (AIP) is a valuable method of pain control in palliative care. When using CSCI, low-dose methadone as add-on to other opioids might be an option in complex pain situations. This study aimed to investigate the effects, and adverse effects, of CSCI for pain control in dying patients, with particular interest in methadone use. METHODS: This was an observational cohort study. Imminently dying patients with pain, admitted to specialized palliative inpatient wards and introduced on CSCI, were monitored daily by staff for symptoms (Integrated Palliative Care Outcome Scale - IPOS), sedation (Richmond Agitation and Sedation Scale - RASS), performance status (Eastern Cooperative Oncology Group - ECOG) and delirium (Confusion Assessment Method - CAM). RESULTS: Ninety-three patients with a median survival of 4 days were included. Of the 47 patients who survived ≥3 days, the proportion of patients with severe/overwhelming pain decreased from 45 to 19% (p < 0.001) after starting CSCI, with only a moderate increase in morphine equivalent daily dose of opioids (MEDD). Alertness was marginally decreased (1 point on the 10-point RASS scale, p = 0.001), whereas performance status and prevalence of delirium, regardless of age, remained unchanged. Both patients with methadone as add-on (MET, n = 13) and patients with only other opioids (NMET, n = 34), improved in pain control (p < 0.05 and 0.001, respectively), despite that MET patients had higher pain scores at baseline (p < 0.05) and were on a higher MEDD (240 mg vs.133 mg). No serious adverse effects demanding treatment stop were reported. CONCLUSIONS: CSCI via AIP is an effective way to reduce pain in dying patients without increased adverse effects. Add-on methadone may be beneficial in patients with severe complex pain.

The Use of 20% Subcutaneous Immunoglobulin Replacement Therapy in Patients With B Cell Non-Hodgkin Lymphoma With Humoral Immune Dysfunction After Treatment With Rituximab.

BACKGROUND: Rituximab is an anti-CD20 chimeric antibody used to treat autoimmune conditions and B cell neoplasms. We characterized immunoglobulin (Ig) levels and vaccine responses in rituximab-treated B cell non-Hodgkin lymphoma (NHL) patients. Patients with impaired vaccine responses were offered therapy with 20% subcutaneous (subq) Ig. PATIENTS AND METHODS: Patients with a biopsy-proven diagnosis of B cell NHL who had received rituximab within the past 24 months were eligible for the study and underwent the following immune evaluation: serum IgG, IgM, IgA, IgE, T/B cell lymphocyte panel, and pre/post vaccine IgG titers to diphtheria, tetanus, and streptococcus pneumoniae. Patients were vaccinated with tetanus, diphtheria and pneumococcal polysaccharide vaccine. Patients with abnormal vaccine responses were offered prophylactic subq Ig for 52 weeks. RESULTS: Fifteen patients with NHL were enrolled in the study. The median IgG was 628 mg/dL [interquartile range, 489-718 mg/dL]. Three (20%) of 15 patients responded to diphtheria vaccination, 1 (6.7%) of 15 responded to tetanus vaccination, and 3 (20%) of 15 responded to vaccination to streptococcus pneumoniae. Thirteen (86.7%) of 15 met criteria for humoral immunodeficiency. Ten patients received subq Ig, and experienced a significant increase in serum IgG (P = .008). There were no serious adverse events, and there was a decrease in nonneutropenic infections while on subq Ig therapy. CONCLUSIONS: Patients with NHL treated with rituximab may have significant humoral immunodeficiency as defined by abnormal vaccine responses even in the setting of relatively normal IgG levels. For these patients, subq Ig replacement therapy is well-tolerated and efficacious in improving serum IgG, and may decrease reliance on antibiotics for the treatment of nonneutropenic infections.

Differential expression of nicotine withdrawal as a function of developmental age in the rat.

Cigarette smoking and resultant nicotine dependence remain major public health problems. Most smokers begin before the age of 18, yet preclinical models have insufficiently characterized the development of nicotine dependence in adolescence. To categorize the short-term effects of chronic nicotine administration throughout adolescence and adulthood, we exposed male Sprague Dawley rats to 14 days of continuously delivered nicotine (0, 1.2 or 4.8 mg/kg/d) using a subcutaneous osmotic minipump, starting between postnatal day 33 (p33) and p96. Next, to explore the effects of extended exposure to chronic nicotine, we exposed male Sprague Dawley rats to 42 days of continuous nicotine starting in adolescence (p33) or early adulthood (p68). Somatic and affective signs of precipitated withdrawal (PW) were observed after a mecamylamine (1.5 mg/kg, i.p.) challenge as compared to a saline injection. Short term nicotine exposure starting at p96, well within the adult period, elicited a significant increase in somatic PW as measured by a composite behavioral score. In contrast, adolescent exposure to nicotine elicited a unique behavioral profile, dependent on the starting age of exposure. Late adolescence exposure was characterized by scratching while adult exposure was characterized by facial tremors and yawns. Extended exposure to nicotine resulted in age specific characteristic nicotine withdrawal behaviors, including scratches, ptosis and locomotion, distinct from the short-term exposure. Thus, nicotine dependence severity, based on the expression of total somatic PW behaviors, is not observed until the adult period, and differences between adolescents and adults are observed using a more nuanced behavioral scoring approach. We conclude that age of nicotine initiation affects somatic withdrawal signs and their magnitude. These data serve as a foundation for understanding the underlying brain mechanisms of nicotine dependence and their development over adolescence and early adulthood.

Using the MEDiPORT humanoid robot to reduce procedural pain and distress in children with cancer: A pilot randomized controlled trial.

BACKGROUND: Subcutaneous port needle insertions are painful and distressing for children with cancer. The interactive MEDiPORT robot has been programmed to implement psychological strategies to decrease pain and distress during this procedure. This study assessed the feasibility of a future MEDiPORT trial. The secondary aim was to determine the preliminary effectiveness of MEDiPORT in reducing child pain and distress during subcutaneous port accesses. METHODS: This 5-month pilot randomized controlled trial used a web-based service to randomize 4- to 9-year-olds with cancer to the MEDiPORT cognitive-behavioral arm (robot using evidence-based cognitive-behavioral interventions) or active distraction arm (robot dancing and singing) while a nurse conducted a needle insertion. We assessed accrual and retention; technical difficulties; outcome measure completion by children, parents, and nurses; time taken to complete the study and clinical procedure; and child-, parent-, and nurse-rated acceptability. Descriptive analyses, with exploratory inferential testing of child pain and distress data, were used to address study aims. RESULTS: Forty children were randomized across study arms. Most (85%) eligible children participated and no children withdrew. Technical difficulties were more common in the cognitive-behavioral arm. Completion times for the study and needle insertion were acceptable and >96% of outcome measure items were completed. Overall, MEDiPORT and the study were acceptable to participants. There was no difference in pain between arms, but distress during the procedure was less pronounced in the active distraction arm. CONCLUSION: The MEDiPORT study appears feasible to implement as an adequately-powered effectiveness-assessing trial following modifications to the intervention and study protocol. ClinicalTrials.gov NCT02611739.

The current evidence base for the feasibility of 48-hour continuous subcutaneous infusions (CSCIs): A systematically-structured review.

BACKGROUND: A continuous subcutaneous infusion (CSCI) is an effective method of multiple drug administration commonly encountered in end of life care when the oral route is compromised. At present, current practice is to limit syringe driver infusion time to a maximum of 24 hours as dictated by available chemical stability data. However, the ability to deliver prescribed medication by a CSCI over 48 hours may have numerous benefits in both patient care and health service resource utilisation. AIM: To examine and present the current evidence base for the stability of 48-hour multiple-drug CSCIs in current clinical practice. DESIGN: A systematically-structured review following PRISMA guidelines. DATA SOURCES: Three electronic databases and the grey literature were searched with no time limits. Empirical studies reporting data on the chemical stability of continuous subcutaneous infusions or solutions stored in polypropylene syringes were included. RESULTS: Twenty-one empirical studies were included in this review reporting chemical compatibility and stability of 32 discrete combinations of twenty-four drugs tested at a variety of different drug concentrations. The majority of combinations reported were assessed as being chemically compatible. The greatest risk of clinically significant chemical degradation was observed with midazolam. Only one study reported the microbiological stability of the solution examined. CONCLUSIONS: There is currently limited evidence for the physical, chemical and microbiological stability of solutions for continuous subcutaneous infusion over a period of 48 hours. More stability data is required before the use of 48-hour CSCIs can be evaluated for use within clinical practice.

Efficacy, safety and pharmacokinetics of subcutaneous azacitidine in Chinese patients with higher risk myelodysplastic syndromes: Results from a multicenter, single-arm, open-label phase 2 study.

BACKGROUND: Azacitidine safety and efficacy were established in studies of mainly Caucasian patients. Differences in drug metabolism enzymes between Caucasian and East Asian populations prevent extrapolation of drug effects between these groups. This phase 2 study evaluated azacitidine safety, efficacy and pharmacokinetics in patients with higher-risk myelodysplastic syndromes (HR-MDS) in mainland China. METHODS: Patients aged ≥18 years with HR-MDS were to receive subcutaneous azacitidine 75 mg/m2 /day for 7 days per 28-day cycle, for ≥6 cycles. Pharmacokinetic blood samples were collected in cycle 1 predose on days 5-7, and postdose on day 7. Pharmacokinetic outcomes are descriptively compared with those of a historical North American cohort. RESULTS: Of 72 participants, 46 (64%) completed ≥6 cycles. Response rate was 96%, driven primarily by stable disease (94%); one patient achieved complete remission. Hematologic improvement was attained by 53% of patients. Azacitidine mean plasma concentration versus time profiles were similar in shape for Chinese (n = 12) and North American (n = 45) patients. Maximum plasma concentration (Cmax ) was higher in Chinese patients; however, mean azacitidine exposure (1190 ng·h/mL) was similar to the North American cohort (1021 ng·h/mL). Most common grade 3-4 treatment-emergent adverse events (TEAEs) were thrombocytopenia (69%) and neutropenia (67%). CONCLUSIONS: Azacitidine was safe and effective in Chinese patients with HR-MDS. Clinical outcomes were comparable to those for primarily Caucasian patients in the phase 3 AZA-001 study. Cmax differences between Chinese and North American patients were not associated with differences in TEAE frequency or severity. No initial azacitidine dose adjustment is required for Chinese patients with HR-MDS.

Identification of drug combinations administered by continuous subcutaneous infusion that require analysis for compatibility and stability.

BACKGROUND: A continuous subcutaneous infusion (CSCI) delivered via syringe pump is a method of drug administration used to maintain symptom control when a patient is no longer able to tolerate oral medication. Several classes of drugs, such as opioids, antiemetics, anticholinergics, antipsychotics and benzodiazepines are routinely administered by CSCI alone or in combinations. Previous studies attempting to identify the most-common CSCI combinations are now several years old and no longer reflect current clinical practice. The aim of this work was to review current clinical practice and identify CSCI drug combinations requiring analysis for chemical compatibility and stability. METHODS: UK pharmacy professionals involved in the delivery of care to palliative patients in hospitals and hospices were invited to enter CSCI combinations comprised of two or more drugs onto an electronic database over a 12-month period. In addition, a separate Delphi study with a panel of 15 expert healthcare professionals was completed to identify a maximum of five combinations of drugs used to treat more complex, but less commonly encountered symptoms unlikely to be identified by the national survey. RESULTS: A total of 57 individuals representing 33 separate palliative care services entered 1,945 drug combinations suitable for analysis, with 278 discrete combinations identified. The top 40 drug combinations represented nearly two-thirds of combinations recorded. A total of 23 different drugs were administered in combination and the median number of drugs in a combination was three. The Delphi study identified five combinations for the relief of complex or refractory symptoms. CONCLUSION: This study represents the first step towards developing authoritative national guidance on the administration of drugs by CSCI. Further work will ensure healthcare practitioners have the knowledge and confidence that a prescribed combination will be both safe and efficacious.

Efficacy, safety, and pharmacokinetics of subcutaneous azacitidine in Taiwanese patients with higher-risk myelodysplastic syndromes.

AIM: Clinical and pharmacokinetic effects of azacitidine in higher-risk myelodysplastic syndromes were established in mainly Caucasian populations. Because of inter-ethnic genotype variability of drug-metabolizing enzymes, it is important to evaluate azacitidine in populations expected to use the drug. METHODS: In this single-arm study, Taiwanese patients with higher-risk myelodysplastic syndromes received azacitidine 75 mg/m2 /day for 7 days/28-day cycle for up to six cycles. Response-evaluable patients had baseline and cycle 6 marrow assessments. Clinical outcomes are compared descriptively with those from a phase 3 study comprising mainly Caucasian patients (N = 179). Pharmacokinetics in a subgroup of Taiwanese patients are descriptively compared with a historical control of North American patients (N = 45). RESULTS: Median age of Taiwanese patients (N = 44) was 64 years (range 36-90), and 46% had poor cytogenetics. Median number of azacitidine cycles was six (1-6). No response-evaluable patient (n = 33) achieved complete or partial remission; however, 22 patients (50%) achieved hematologic improvement, 12 of 32 patients attained RBC transfusion independence and 7 of 18 attained platelet transfusion independence. Most common grade 3-4 treatment-emergent adverse events were neutropenia (52%) and leukopenia (39%). Pharmacokinetic profiles were similar for Taiwanese (N = 12) and North American (N = 45) patients. Maximum plasma concentration was higher in Taiwanese patients; however, mean azacitidine exposure was within the range for North American patients. CONCLUSION: These data confirm the safety and efficacy of azacitidine in Taiwanese patients with higher-risk myelodysplastic syndromes. Clinical outcomes were generally comparable with those for Caucasian patients. No meaningful differences in azacitidine pharmacokinetics were observed for Taiwanese patients, and no initial dose adjustment is necessary.

Subcutaneous Immunoglobulin in Oncology Clinical Practice.

The administration of gammaglobulin as replacement therapy to boost immune function in patients with immunodeficiency secondary to malignancy is traditionally given in the IV formulation. A pilot program at a large Canadian cancer center led by an advanced practice nurse (APN) demonstrated that transitioning patients to home-based, self-administered subcutaneous infusions (subcutaneous immunoglobulin [SCIG]) led to savings and benefits for patients and the institution. The implementation of SCIG in oncology by an APN is a novel and innovative patient-centered approach to supportive care.

Novel intrathecal and subcutaneous catheter delivery systems in the mouse.

BACKGROUND: Catheter systems that permit targeted delivery of genes, molecules, ligands, and other agents represent an investigative tool critical to the development of clinically relevant animal models that facilitate the study of neurological health and disease. The development of new sustained catheter delivery systems to spinal and peripheral sites will reduce the need for repeated injections, while ensuring constant levels of drug in plasma and tissues. NEW METHOD: Here, we introduce two novel catheter delivery systems in the mouse: the O'Buckley intrathecal catheter system for sustained delivery to the spinal region and a subcutaneous bifurcated catheter system for sustained drug delivery to both hindpaws. RESULTS: The O'Buckley intrathecal catheter system consistently distributed Evans Blue throughout the spinal cord, with the greatest concentration at the thoracic region, and with an 85% surgery success rate. The subcutaneous catheter system consistently distributed Evans Blue to the hindlimbs, with a 100% surgery success rate. COMPARISON TO EXISTING METHOD: The O'Buckley intrathecal catheter system accomplishes sustained drug delivery to the spinal region, with a 2-fold increase in surgery success rate, as compared to the traditional method. Our subcutaneous bifurcated catheter system accomplishes sustained drug delivery to both hindpaws, eliminating the need for repeated intraplantar injections. CONCLUSIONS: We have developed catheter systems that improve upon traditional methods in order to achieve sustained localized drug delivery to spinal tissues and to hindpaw tissues surrounding peripheral sciatic nerve terminals. These methods have a broad reach, and can be used to enhance behavioral, physiologic and mechanistic studies in mice.

The development and evaluation of a subcutaneous infusion delivery system based on osmotic pump control and gas drive.

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 CO2 gas, 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 was Y = 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 vivo results 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.

Feasibility of subcutaneous gentamicin and pressurized irrigation as adjuvant strategies to reduce surgical site infection in colorectal surgery: results of a pilot study.

Surgical site infections (SSIs) remain a common and costly morbidity after colorectal surgery. This rate remains high even in the setting of strict adherence to Surgical Care Improvement Project Protocols. The aim of our pilot study was to determine the feasibility and safety of subcutaneous gentamicin injection or pressurized irrigation as adjuncts to reduce SSI. A total of 132 patients who underwent colorectal surgery at the VA North Texas Health Care System were prospectively assigned to a pressurized irrigation group (n = 44), a preincision gentamicin injection group (n = 48), or control (n = 40). The primary objective was to assess safety and feasibility of these strategies. Patient demographics were matched among groups. Univariate and multivariate analyses were performed to identify possible predictions of SSI in this cohort. The rate of SSI in the control group was 25 per cent, 13.5 per cent in the pressurized irrigation group, and 12.5 per cent in the gentamicin group (P = 0.26). Combined, the intervention groups had a 13 per cent SSI versus 25 per cent control (P = 0.09). Operative time was not increased by the interventions and no intraoperative complications specifically related to the interventions were noted. Postoperative complications were not different between groups. Both albumin and body mass index were associated with SSI. Body mass index was and independent predictor of SSI (P = 0.006). In conclusion, this pilot study demonstrates the feasibility of the interventions described. There was no detrimental effect of either intervention. There was trend toward a reduction in SSI in the intervention group, which warrants further investigation.

Evaluation of diabetic patients after three month use of continuous subcutaneous insulin infusion, dispensed by a protocolled form at outpatient reference clinic of Taguatinga Regional Hospital

Objective To evaluate the data of continuous subcutaneous insulin infusion protocol (CSII) for diabetics waived by the Health State Secretariat of Distrito Federal (HSSDF) and therapeutic responses three months after the transfer of multiple daily injections regimen for CSII. Subjects and methods Eighty patients (49 female) took part in this experimental study, mean age and disease duration were 27.9 years and 13 years, respectively; 96% patients had type 1 diabetes mellitus. Results The entire sample (ECO) and 3 subgroups (group 1 – A1c decrease, group 2 – A1c stable, and group 3 – A1c increase), stratified according to a ≥ 0.5% change in A1c, were analyzed. Group 1 involved 64% of the patients. The ECO showed a significant A1c decrease: MDI 8.1 ± 1.4% vs. CSII 7.3 ± 0.9%, p < 0.0001 (0.8% difference pro CSII therapy). Group 1 demonstrated an A1c decrease from 8.7% to 7.3% (1.4% difference). Group 2 mean A1c was 7.1%. Rate of hypoglycemia (< 50 mg/dL) decreased 61% in the ECO and 79% in Group 2. Conclusion This study reinforces the safety and efficacy of CSII with a robust A1c reduction and hypoglycemia. The pioneer care HSSDF ambulatory attests to be achievable the free dispensing by Unified Health System (UHS) following a protocol, and this approach results in less wastage to the patient and represents a rational policy of therapy with CSII for UHS. Arch Endocrinol Metab. 2015;59(1):23-8 .

Hyperandrogenism in adolescent girls with type 1 diabetes mellitus treated with intensive and continuous subcutaneous insulin therapy.

INTRODUCTION: Women with type 1 diabetes mellitus (T1DM) experience high prevalence of hyperandrogenic disorders. The aim of this study was to evaluate hormonal profile with respect to hyperandrogenic disorders in adolescents with T1DM. MATERIAL AND METHODS: Forty seven adolescent girls with T1DM were evaluated and compared to 19 healthy and 21 non-diabetic girls with polycystic ovary syndrome (PCOS). In all subjects, basal and GnRH analogue stimulated androgens, gonadotropins and SHBG were measured and ultrasonography of ovaries was performed. RESULTS: Girls with T1DM experienced first menses significantly later than healthy controls [13.1 (12.0-14.0) v. 12.0 (11.0-12.0) years, p = 0.02]. Nine (19.2%) of them fulfilled PCOS criteria (T1DM+PCOS). They had significantly mean HbA1c from the diagnosis of T1DM than T1DM girls with no PCOS [6.7 (6.6-7.2) v. 7.3(6.4-7.8)%, p = 0.049]. Hormonal profile, hirsutism score and ovarian volume did not differ significantly between the two groups. HbA1c at the study point and mean HbA1c for the last 12 months correlated negatively with SHBG level (r = -0.5, p = 0.006; r = -0.04, p = 0.02). T1DM+PCOS girls had significantly lower FAI [3.0 (2.6-4.3) v. 8.6 (6.5-10.8), p = 0.04] and ovarian volume than non-diabetic PCOS girls [4.6 (2.7-5.2) v. 7.4 (4.3-10.0) mL, p = 0.007]. CONCLUSIONS: Clinical symptoms of PCOS in adolescent girls with T1DM are milder than in non-diabetic peers, probably due to the protective role of higher SHBG resulting in lower free androgen level.

Renal protection: preconditioning for the prevention of contrast-induced nephropathy.

As the numbers of interventional procedures are rising exponentially, identification of those patients at risk for renal complications has become even more important. Renal complications have been associated with increased morbidity and mortality after interventions. Risk factors have been studied to help identify those patients at increased risk for developing contrast-induced nephropathy. Hydration and medications have been studied as protective measures to decrease risk of renal complications. Preconditioning patients with intravenous hydration has been found to be the most helpful in circumventing postprocedural contrast-induced nephropathy.

Evaluation of a single subcutaneous infusion of carboplatin as adjuvant chemotherapy for dogs with osteosarcoma: 17 cases (2006-2010).

OBJECTIVE: To evaluate adverse effects and survival times in dogs with osteosarcoma that received a single SC infusion of carboplatin as adjunctive chemotherapeutic treatment following limb amputation or limb-sparing surgery. DESIGN: Retrospective case series. ANIMALS: 17 client-owned dogs with spontaneously occurring osteosarcoma. PROCEDURES: Medical records of dogs that underwent limb amputation or limb-sparing surgery followed by a single continuous SC infusion of carboplatin (total dose, 300 mg/m(2) infused over 3, 5, or 7 days) were evaluated. Signalment, tumor location, type of surgery (amputation or limb-sparing), duration of carboplatin infusion, results of hematologic and serum biochemical analyses, and adverse effects were recorded. Kaplan-Meier survival analysis was performed. RESULTS: Median survival time for all dogs was 365 days. Nine dogs had adverse bone marrow-related (hematologic) effects, 1 had adverse gastrointestinal effects, and 7 had infections at the surgical site. No significant differences were detected in survival times of dogs grouped according to tumor location, type of surgery, duration of carboplatin infusion, or development of postoperative infection. CONCLUSIONS AND CLINICAL RELEVANCE: Median survival time and adverse effects in dogs with osteosarcoma that received a single SC infusion of carboplatin over a 3-, 5-, or 7-day period as adjunctive treatment following limb amputation or limb-sparing surgery were comparable to those of previously reported chemotherapy protocols requiring IV drug administration over several weeks. Further investigation is needed to evaluate the efficacy of this protocol as adjunctive treatment for osteosarcoma and other tumors in dogs.

Subcutaneous infusion in palliative care: the neria soft infusion set.

Patients approaching the end of their life may be unable to tolerate the administration of oral medication owing to their underlying disease and/or symptoms, such as nausea and vomiting. Subcutaneous infusion is an alternative route of administration that offers a number of advantages over oral and intravenous routes. This product focus article provides an overview of subcutaneous infusion, including how the selection of the most appropriate infusion device can greatly contribute to the overall comfort of the patient. This in turn minimises the potential for premature device loss, which can lead to repeated insertion procedures for the patient, increases the potential for infection, and has resource implications. The article then describes the recently developed neria soft infusion set, as well as providing case studies of its use.