Minimal Nausea Research Articles

A Study to Assess the Quality of Life and Its Clinical and Psychological Determinants among Cancer Patients Receiving Chemotherapy at Selected Hospitals of Bagalkot

A Study to Assess the Quality of Life and Its Clinical and Psychological Determinants among Cancer Patients Receiving Chemotherapy at Selected Hospitals of Bagalkot

A Phase 2 Evaluation of a Novel Co-Formulation of Pramlintide and Regular Insulin to Improve Postprandial Glycemic Control in Adults with Type 1 Diabetes (T1D)

Objective: Pramlintide co-administration, used in conjunction with prandial insulin, has substantial clinical benefits to improve post-prandial glucose excursions, glycemic variability (GV) and time in range (TIR), but is associated with an increased injection burden that adversely affects adherence and persistence. A novel, fixed-ratio co-formulation of pramlintide and regular insulin (XP-3924) was evaluated in a phase 2 single injection study measuring XP-3924 pharmacokinetics (PK), glucose pharmacodynamics (PD), and its effects upon overall glycemic control. Methods: This was a Phase 2 randomized, open-label, active comparator-controlled, three-period cross-over study, which enrolled 18 adults with T1D to compare the PK and PD, glycemic affects and safety and tolerability of a single dose of XP-3924, to co-administration of regular insulin (Humulin® R) and pramlintide (Symlin®), and to an injection of regular insulin (RI) alone. Subjects were randomly allocated to a sequence of three treatments: XP-3924 (with 50% insulin reduction based their insulin to carbohydrate ratio), RI, or co-administration (RI with 50% insulin reduction plus a comparable pramlintide dose, co-administered as separate injections). The study drugs were administered subcutaneously 30 minutes before a 75-gram oral glucose challenge and glucose levels were monitored for 6 hours. Results: XP-3924 treatment resulted in a 62.3% reduction of hyperglycemia (blood glucose AUC0-3 hr >180 mg/dL) after the glucose challenge when compared to RI (p<0.001), and exhibited comparable postprandial glycemic control to that of the co-administration. After the oral glucose challenge, the mean absolute change in blood glucose and was less in XP-3924 when compared to both co-administration and to RI (197.7±70.74 mg/dL, 230.5±162.39 mg/dL, 254.2±195.21 mg/dL, respectively), as well as GV as defined by the comparison of the intrasubject coefficient of variation of plasma glucose readings across study treatments (53.3%, 62.1%, 71.0%, respectively). The PK of Pramlintide in XP-3924 when compared to co-administration, exhibited longer median Tmax [40.5 (range 21.0–150.0) minutes versus 10.0 (range 10.0–24.0) minutes, respectively], and comparable AUC0-360. The incidence and severity of treatment emergent adverse events (e.g., injection site reactions, minimal nausea and vomiting) was comparable across all treatment arms with no drug-related serious adverse events. Conclusion: XP-3924 was well tolerated and significantly improved post-prandial glucose excursions and glycemic variability compared to regular insulin. XP-3924 also exhibited a favorable PK and PD profile and may be a viable alternative to insulin and pramlintide co-administration to improve treatment adherence and overall glycemic control, especially after meals, addressing an unmet need in the clinical care of people with type 1 diabetes.

The Patient-Reported Outcome of Intra-Operative Direct Vision Pectoral Nerve Block for Postoperative Analgesia for Breast Surgery

Background and Aims: Pectoral nerve blocks gained increasing recognition for adequate postoperative pain relief following breast surgery. Traditionally, anaesthetist administered preoperatively under ultrasound guidance, which added significantly to the total procedure time. We studied the effectiveness of intraoperative direct vision pectoral nerve block and reduction of total theatre time. Methods: We provided questionnaires to the eligible patients who underwent a mastectomy and or axillary node clearance from August 2018 to May 2019. All the patients had an intra-operative pectoral 1 and serratus plane (Pecs) block. Participants documented pain score twice daily, episodes of nausea or vomiting and type and dose of analgesia for the first seven postoperative days. We compiled and grouped the results into postoperative days 1 - 2 and 3 - 7 for data analysis. Results: Patients reported generally low levels of pain, with a median pain score of 1.75 out of 10 for postoperative days 1 - 2 (IQR 4). The score decreased to 0.7 for days 3 - 7 postoperatively (IQR 3) suggesting that most patients had generally minimal levels of pain apart from a few outliers. The average injection time for PECs blocks was 5 minutes, significantly less than USS guided techniques of 20 - 30 minutes. Conclusions: Our data suggest that nerve blocks under direct vision offer satisfactory efficacy in postoperative analgesia with minimal nausea and vomiting. This is in addition to substantial benefits in operative efficiency and reduction of total procedure time.

S2855 New Onset Gastrointestinal Involvement in Systemic Mastocytosis

INTRODUCTION: Mastocytosis is a rare hematopoietic disorder that results from abnormal clonal proliferation of mast cells. Bone marrow biopsy is a major criterion for diagnosis of systemic disease, with molecular markers fulfilling minor criteria. Mastocytosis can present with isolated cutaneous involvement, as solid tumors, or with systemic involvement. It can also have gastrointestinal (GI) involvement, however, non-specific clinical signs and subtle histological findings make it a challenging diagnosis. CASE DESCRIPTION/METHODS: A 33 year old female with a history of seasonal allergies and eczema initially presented to the dermatology clinic for urticaria pigmentosa that led to skin and bone biopsy confirming mild systemic mastocytosis. Six years later, she presented to the GI clinic with six months of non-radiating epigastric burning and gnawing pain, associated with bloating, minimal nausea and diarrhea, and twenty-pound unintentional weight loss. She had no dietary or appetite changes, no emesis or major bowel movement changes. At the time, she was not on any medications for mastocytosis. Serum serologies including CBC, CMP, TSH were within normal limits. Celiac panel was normal, but did show elevated immunoglobulin A of 344 mg/dL. Tryptase level was 18.9. CT abdomen pelvis with contrast did not reveal GI malignancies. Upper endoscopy was normal with biopsies taken. Pathology showed increased mast cells in the lamina propria of both the gastric and duodenal mucosa. Immunostains for CD117 and mast cell tryptase showed > 50/HPF mast cells in the lamina propria. Overall, findings are consistent with mastocytosis involving the GI tract. Patient was subsequently referred to immunology and started on cromolyn. DISCUSSION: The authors describe a case of GI infiltration of mastocytes in a patient with prior bone marrow biopsy confirmed systemic mastocytosis, previously only prescribed epinephrine for the feared complication of anaphylaxis. Her presentation to the GI clinic was highly suspicious for mastocyte extension to the GI tract; however a full workup to rule out malignancy was needed given her red flag symptoms. Pathology ultimately confirmed GI extension of mastocytosis. This case highlights the importance of interdisciplinary approach to systemic diseases. Although her GI complaints started more than five years after her initial diagnosis, high index of suspicion and thorough evaluation led to a timely unifying diagnosis that led to timely treatment and ultimately complete symptom resolution.Figure 1.: Duodenum, H&E 400x. Neoplastic mast cells are usually difficult to distinguish on H&E stained sections when not mass forming, but characteristic features include an elongate to ovoid nucleuscontaining smooth chromatin and inconspicousnucleoli, with a moderate amount of pale staining cytoplasm (arrows), distorting the normal mucosal architecture. They can be associated with an influx of eosinophils and/or plasma cells as well.Figure 2.: Immunohistochemistry staining of mucosa. Mast cells scattered throughout the mucosa in increased numbers without the formation of discreet and compact clusters that is typically seen in GI mastocytosis. Affected cells aberrantly co-express CD117 and CD25 to confirm diagnosis of systemic mastocytosis.

Intrathecal Opioid Dosing During Spinal Anesthesia for Cesarean Section: An Integrative Review.

Approximately one in three women in the United States deliver via Cesarean section (CS), making it one of the most common surgical procedures in the country. Neuraxial (spinal or epidural) anesthesia is the most effective and common anesthetic approach for pain relief during a CS in the United States and often associated with adverse effects such as nausea, vomiting, and pruritus. While recommended dose ranges exist to protect patient safety, there are a lack of guidelines for opioid doses that both optimize postoperative pain management and minimize side effects. This integrative review synthesizes the evidence regarding best practice of opioid dosing in neuraxial anesthesia for planned CS. Evidence supports the use of lower doses of intrathecal (IT) opioids, specifically 0.1 morphine, to achieve optimal pain management with minimal nausea, vomiting, and pruritus. Lower IT doses have potential to achieve pain management and to alleviate preventable side effects in women delivering via CS.

Randomized, Placebo-Controlled, Phase III Trial of Fosaprepitant, Ondansetron, Dexamethasone (FOND) Versus FOND Plus Olanzapine (FOND-O) for the Prevention of Chemotherapy-Induced Nausea and Vomiting in Patients with Hematologic Malignancies Receiving Highly Emetogenic Chemotherapy and Hematopoietic Cell Transplantation Regimens: The FOND-O Trial

Evidence supports olanzapine for prophylaxis of chemotherapy-induced nausea/vomiting (CINV) for highly emetogenic chemotherapy; however, most studies focus on solid malignancies and single-day regimens. A randomized, double-blinded, placebo-controlled trial was conducted to compare the addition of olanzapine to triplet therapy (fosaprepitant, ondansetron, dexamethasone [FOND-O]) versus triplet therapy alone (FOND) in preventing CINV in hematology patients receiving single-day and multiple-day highly emetogenic chemotherapy and hematopoietic cell transplant (HCT) regimens (NCT02635984).The primary objective of this study was to compare complete response (CR; no emesis and minimal nausea, <25 mm on a 100-mm visual analog scale) during the overall assessment period (chemotherapy days plus 5 days after). Secondary objectives were the number of emesis, number of rescue medications, percent achieving minimal nausea, and percent achieving complete protection (CP; no emesis, rescue antiemetic, or significant nausea), all of which are reported as acute (chemotherapy days), delayed (5 days after chemotherapy), and overall phases. Olanzapine 10 mg or matching placebo were given on each chemotherapy day and 3 days after. Adults with hematologic malignancy receiving HCT regimens of melphalan, BEAM (carmustine, etoposide, cytarabine, melphalan), busulfan (Bu)/cyclophosphamide (Cy), Bu/fludarabine (Flu), Bu/melphalan, FluCy, FluCy-total body irradiation (TBI), etoposide-TBI, and ICE (ifosfamide, carboplatin, etoposide) or 7+3 chemotherapy regimens were included. An estimated 98 patients were required using alpha = .05 and 80% power.No significant differences existed in baseline characteristics between FOND-O (n = 51) and FOND (n = 50) arms. Mean duration of olanzapine was 7.7 days (range, 4 to 11). Discontinuation for possible adverse events occurred in 3 placebo and 0 olanzapine patients. CR was significantly higher for FOND-O in overall (55% versus 26%, P = .003) and delayed (60.8% versus 30%, P = .001) but not acute (P = .13) phases. Significantly more patients receiving FOND-O achieved no more than minimal nausea in overall (P = .001) and delayed phases (P = .0002), as well as fewer overall mean emesis counts (P = .005). CP rates were not different in any assessment phase (P ≥ .05 each). Within the HCT subgroup (n = 64), the CR, CP, and no significant nausea rates were significantly better for FONDO-O in overall and delayed phases (all P < .05). Analysis within the HCT subgroup revealed significant improvement in outcomes in delayed and overall phases with FOND-O in the autologous but not allogeneic cohort.Addition of olanzapine to an NK-1–based triplet antiemetic regimen significantly improved clinically relevant outcomes in the HCT population.

Effect of single-dose dexmedetomidine on postoperative recovery after ambulatory ureteroscopy and ureteric stenting: a double blind randomized controlled study

BackgroundAmbulatory surgery has recently gain popularity, as it is a good method of optimizing hospital resources utilization. To support ambulatory surgery, anaesthetic goals now revolve around patients’ early recovery with minimal pain and nausea, expedient discharge home and prompt resumption of activities of daily living. In this study, we evaluated the effect of a single pre-induction dose of dexmedetomidine on anaesthetic requirements, postoperative pain and clinical recovery after ambulatory ureteroscopy andureteric stenting under general anaesthesia.MethodsSixty patients were randomised to receive IV dexmedetomidine 0.5 μg.kg-1 (Group DEX, n = 30) or IV saline (Group P, n = 30). General anaesthesia was maintained with Sevoflurane: oxygen: air, titrated to BIS 40–60. Pain intensity, sedation, rescue analgesics, nausea/vomiting and resumption of daily activities were recorded at 1 h, and postoperative day (POD) 1–5.ResultsGroup DEX patients had significant reduction in sevoflurane minimum alveolar concentration (MAC), mean (SD) DEX vs. Placebo 0.6 (0.2) vs. 0.9 (0.1), p = 0.037; reduced postoperative resting pain at 1 h (VAS 0–10) (mean (SD) 1.00 (1.84) vs. 2.63 (2.78), p = 0.004), POD 1 (mean (SD) 1.50 (1.48) vs. 2.87 (2.72), p = 0.002), POD 2 (0.53 (0.97) vs. 1.73 (1.96), p = 0.001) and POD 3 (0.30 (0.75) vs. 0.89 (1.49), p = 0.001). DEX patients also had less pain on movement POD 1 (3.00 (2.12) vs. 4.30 (3.10), p = 0.043) and POD 2 (2.10 (1.98) vs. 3.10 (2.46), p = 0.040), with higher resumption of daily activities by 48 h compared to placebo, 87% vs. 63%, p = 0.04.ConclusionsWe conclude that a single dose of dexmedetomidine was a useful adjuvant in reducing MAC and postoperative pain (at 1 h and POD 1–3), facilitating faster return to daily activities by 48 h.Trial registrationThe Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12617001120369, 31st July 2017, retrospectively registered.

Anaesthesia for laparoscopic surgery: General vs regional anaesthesia.

The use of laparoscopy has revolutionised the surgical field with its advantages of reduced morbidity with early recovery. Laparoscopic procedures have been traditionally performed under general anaesthesia (GA) due to the respiratory changes caused by pneumoperitoneum, which is an integral part of laparoscopy. The precise control of ventilation under controlled conditions in GA has proven it to be ideal for such procedures. However, recently the use of regional anaesthesia (RA) has emerged as an alternative choice for laparoscopy. Various reports in the literature suggest the safety of the use of spinal, epidural and combined spinal-epidural anaesthesia in laparoscopic procedures. The advantages of RA can include: Prevention of airway manipulation, an awake and spontaneously breathing patient intraoperatively, minimal nausea and vomiting, effective post-operative analgesia, and early ambulation and recovery. However, RA may be associated with a few side effects such as the requirement of a higher sensory level, more severe hypotension, shoulder discomfort due to diaphragmatic irritation, and respiratory embarrassment caused by pneumoperitoneum. Further studies may be required to establish the advantage of RA over GA for its eventual global use in different patient populations.

Patient-controlled epidural analgesia or multimodal pain regimen with periarticular injection after total hip arthroplasty: a randomized, double-blind, placebo-controlled study.

The optimal postoperative analgesia after primary total hip arthroplasty remains in question. This randomized, double-blind, placebo-controlled study compared the use of patient-controlled epidural analgesia (PCEA) with use of a multimodal pain regimen including periarticular injection (PAI). We hypothesized that PAI would lead to earlier readiness for discharge, decreased opioid consumption, and lower pain scores. Forty-one patients received PAI, and forty-three patients received PCEA. Preoperatively, both groups were administered dexamethasone (6 mg, orally). The PAI group received a clonidine patch and sustained-release oxycodone (10 mg), while the PCEA group had placebo. Both groups received combined spinal-epidural anesthesia and used an epidural pain pump postoperatively; the PAI group had normal saline solution, while the PCEA group had bupivacaine and hydromorphone. The primary outcome, readiness for discharge, required the discontinuation of the epidural, a pain score of <4 (numeric rating scale) without parenteral narcotics, normal eating, minimal nausea, urination without a catheter, a dry surgical wound, no acute medical problems, and the ability to independently transfer and walk 12.2 m (40 ft). The mean time to readiness for discharge (and standard deviation) was 2.4 ± 0.7 days (PAI) compared with 2.3 ± 0.8 days (PCEA) (p = 0.86). The mean length of stay was 3.0 ± 0.8 days (PAI) compared with 3.1 ± 0.7 days (PCEA) (p = 0.46). A significant mean difference in pain score of 0.74 with ambulation (p = 0.01; 95% confidence interval [CI], 0.18 to 1.31) and 0.80 during physical therapy (p = 0.03; 95% CI, 0.09 to 1.51) favored the PCEA group. The mean opioid consumption (oral morphine equivalents in milligrams) was significantly higher in the PAI group on postoperative day 0 (43 ± 21 compared with 28 ± 23; p = 0.002) and postoperative days 0 through 2 (136 ± 59 compared with 90 ± 79; p = 0.004). Opioid-Related Symptom Distress Scale (ORSDS) composite scores for severity and bothersomeness as well as scores for nausea, vomiting, and itchiness were significantly higher in the PCEA group (p < 0.05). Quality of Recovery-40 scores and patient satisfaction were similar. PAI did not decrease the time to discharge and was associated with higher pain scores and greater opioid consumption but lower ORSDS scores compared with PCEA. The choice for analgesic regimen may depend on a particular patient's threshold for pain and the potential side effects.

Robust Immune Reconstitution in Children with Severe Primary Immunodeficiency after Reduced-Intensity Conditioning Hematopoietic Stem Cell Transplantation

Hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for severe primary immunodeficiency diseases (PID), but it is still unclear what is the optimal transplant approach. To help answer this question, the stem cell transplant team at Ann & Robert H. Lurie Children’s Hospital of Chicago (formerly Children’s Memorial Hospital) evaluated the risks and benefits of a reduced-intensity conditioning (RIC) transplant approach for treatment of severe PID. Between 2000 and 2013, 42 children with severe PID were treated with allogeneic HSCT following a RIC regimen consisting of fludarabine (30mg/m2/day x 6), rabbit anti-thymocyte globulin (once daily x 4), and intravenous busulfan (once daily x 2). Total busulfan exposure, as measured by the plasma concentration-time area-under-the-curve (AUC), was targeted individually for each patient at 4000 µM*min/day in an earlier cohort (n=14), and 5000 in a later cohort (n=28). Patients were treated in an ambulatory setting and were hospitalized only for specific medical or social reasons. There were 31 male and 11 female patients. The median age at the time of transplant was 8.2 months (range 1 month-17.4 years). The median weight was 7.6 kg (range 2.5-81.5 kg). Patients were diagnosed with severe combined immunodeficiency (n=17), Wiscott-Aldrich syndrome (n=7), hyper-IgM syndrome (n=5), major histocompatibility complex II deficiency (n=3), X-linked lymphoproliferative disease (n=3), NEMO syndrome (n=2), Omenn syndrome, reticular dysgenesis, Chediak-Higashi syndrome, IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) syndrome, and IPEX-like syndrome (n=1 each). Fourteen patients had related donors and 28 had unrelated donors. Twenty-eight patients received peripheral blood HSC, 12 received cord blood, and 2 received bone marrow as the source of HSC. All patients tolerated the conditioning regimen with minimal nausea, vomiting, or pain. No severe mucositis, sinusoidal occlusion syndrome, seizure, grade III/IV acute GVHD or extensive chronic GVHD were seen. In most patients, the engraftment was rapid, with ANC ≥ 500 at a median of +15 days post-transplant, following a nadir at day +10 with a median ANC nadir of 60. In the AUC 4000 cohort, 2 patients (14%) developed primary graft failure and 2 patients (14%) developed immune-mediated secondary graft failure; in the AUC 5000 cohort, 2 patient (7%) developed primary graft failure and 1 patient developed secondary graft failure after primary EBV infection. Two patients died from complications associated with primary graft failure, 2 from complications caused by EBV infections, and 2 from complications related to their underlying diseases in the early post-transplant period. Kaplan–Meier analysis shows overall and event-free survival rates of 81.9% and 73.6%, respectively, at a median follow-up of 4.3 years. Most engrafted patients have stable donor chimerism over time. At a mean of 3.5 years post-transplant, the median donor chimerism in total white blood cells was 97% and the first and third quartiles were 77% and 99%, respectively. Engrafted patients demonstrated robust immune reconstitution with B and T cell counts normalized by 3 months and 9 months post-transplant, and CD45RA+ naive T cells by 1 year. Between 1 to 4 years post-transplant, the median absolute CD4+, CD8+ and CD19+ cell counts were 1388, 976 and 720 per mm3, respectively, percentage of CD45RA+ naive CD4 and CD8 cells were 68% and 81%, and endogenous IgG and IgM levels were 840 and 97 mg/dL. T cells showed regular responses to antigen and mitogen stimulation and exhibited normal TCRVβ repertoires. Endogenous IgG levels returned to normal by day +100, and no intravenous immunoglobulin infusion was required after day +100 in all but 1 patients. Positive vaccine-specific antibody responses were seen in patients after reimmunization at 12-24 months post-transplant. Clinically, patients have normal growth and development and do not exhibit increased susceptibility to infection. Our data showed that HSCT after RIC offers an optimal treatment for severe PID by providing robust post-transplant immune reconstitution while minimizing side effects. To reduce the risk of graft failure, we recommend a targeted busulfan AUC of 5000 µM*min/day for 2 days. DisclosuresNo relevant conflicts of interest to declare.

Orally Inhaled Dihydroergotamine: A Review

Orally inhalable dihydroergotamine (iDHE), before the US Food and Drug Administration in 2013 for consideration for approval for acute treatment of episodic migraine in adults, is a user-friendly formulation of an older medication. Dihydroergotamine (DHE) has a heterogeneous receptor profile, central penetration, and persistent receptor binding that may account for its clinical prolonged benefits in acute treatment of migraine. The same features may result in the ability of DHE to reverse central sensitization and allodynia and to maintain efficacy deep into attacks. These characteristics make DHE particularly useful in treating migraine upon awakening, prolonged migraine and status migrainosus, menstrually related migraine, and for bridging patients out of medication-overuse headache/chronic migraine. The inhalable formulation has helpful pharmacokinetics, with a lower maximal serum concentration than intravenous DHE which may account for minimal nausea, and less binding to the potentially toxic serotonin2B receptor. The inhaler itself is designed for delivery of reproducible aliquots of intrapulmonary DHE with only nominal need for patient coordination. The inhalable form allows for bypassing the gastrointestinal tract in the setting of migraine nausea or vomiting, and greatly reduces first-pass effect. No drug-related serious adverse events were reported during the Phase 3 study of iDHE. Product taste and nausea were the most common side effects in both the Phase 3 regulatory trial and in the safety extension trial. Limitations for use of iDHE are those for any ergot or triptan, ie, contraindication in the setting of vascular disease. In addition, iDHE is metabolized by the cytochrome P450 3A4 liver enzymatic system. Inhalable DHE provides the promise of a new formulation of a valued medication with important clinical features, useful deep into attacks in a variety of situations.

Pancreatic Laceration in a Female Collegiate Soccer Athlete: A Case Report

To characterize the diagnosis of pancreatic trauma in an athletic population and to raise awareness among health care providers of the possibility of this life- and organ-threatening injury. An 18-year-old, previously healthy female collegiate soccer athlete sustained a direct blow from an opponent's knee between the left and right upper abdominal quadrants while attempting to head the ball. She initially presented with only minimal nausea and discomfort, but this progressed to abdominal pain, tenderness, spasm, and vomiting. She was referred to the emergency department, where she was diagnosed with a pancreatic laceration. Duodenal, hepatic, or splenic contusion or laceration; hemorrhagic ovarian cyst. The patient underwent a distal pancreatectomy and total splenectomy. Pancreatic injuries, particularly those severe enough to warrant surgical intervention, are extremely rare in athletes. Recognition of a pancreatic injury can be very challenging outside the hospital setting. This is problematic, because a delay in diagnosis is a significant source of preventable morbidity and mortality after this rare injury. Thus, early identification depends on a high index of suspicion, a thorough examination, and close observation. It is imperative that athletic trainers and other health care professionals be able to identify this condition so that referral and management can occur without delay.

A Bird's-Eye View of Fever

A 78-year-old man presented with a 4-month history of worsening fatigue, weakness, and anorexia, with an unintentional weight loss of 11.4 kg. He reported fevers, chills, night sweats, dry mouth, nonproductive cough, dyspnea with minimal exertion, nausea, and postural light-headedness.

Outpatient Decitabine in Elderly Patients with Acute Myeloid Leukemia (AML).

Abstract 4144 BackgroundThe treatment of elderly patients with AML remains controversial due to the inferiority of outcomes associated with standard intensive induction regimens. Hypomethylating agents have been shown to improve quality of life and survival in patients with myelodysplastic syndromes and have activity in AML. We report our experience with decitabine in elderly patients with previously untreated or refractory AML. Patients and methodsWe conducted a retrospective analysis of 30 patients (11 males and 19 females) with AML who were ineligible for intensive induction chemotherapy and received decitabine (20 mg/m2 for 5 days every 28 days). Median age at diagnosis was 67 years (range 40 to 91 years), 28/30 (93.3%) patients were 60 years of age or older. Twelve (40%) patients had cytogenetic abnormalities (7 – unfavorable). ECOG performance status was 0-1 for 26 patients, 2 for 3 patients and 3 for 1 patient. Seven (23.3%) patients had secondary AML and 23 (76.7%) patients had de novo AML, of which 10 demonstrated evidence of multilineage dysplasia on bone marrow biopsy. Eleven (36.7%) patients progressed after prior therapy which included intensive induction therapy in 10 patients (followed by stem cell therapy in 4 patients) and tipifarnib in 1 patient. Nineteen (63.3%) patients received decitabine as first-line therapy. Clearance of blasts from the peripheral blood was monitored and used as an indicator of improved relapse-free survival in AML. Overall survival was defined as the time from the day 1 of decitabine treatment to death. ResultsPatients received a median of 5 cycles of decitabine. Seven patients (23.3%) received ≥10 cycles. All patients received decitabine in the outpatient setting. No hospitalizations were required to administer treatment. Peripheral blood blast clearance was documented in 23 (76.7%) patients including 7 patients who achieved a CR/CRi, and 2 PR. The median time to response was 2 months with median duration of 3 months. Seven patients (23.3%) did not respond to treatment. To date, 19 (63.3%) patients have died after 5-24 months of therapy and 11 (36.7%) remain alive. The median survival was 12 months in all patients (range 4 to 24 months) and 14 months in the 17 patients who received more than 4 cycles of therapy. Overall survival was 82.4% at 6 months and 47.9% at 12 months. Eleven (36.7%) patients survived for >1 year. Seven patients underwent allogeneic stem cell therapy after achieving CR/CRi on decitabine. Three patients received stem cells from siblings or offspring; 3 patients had a matched unrelated donor and 1 patient received umbilical cord stem cells. Three patients are alive after a median follow-up of 12 months. Three patients died of relapsed AML and 1 patient died of infectious complications of transplant.Decitabine was well tolerated. Ten patients experienced minimal nausea amenable to ondansetron with no documented episodes of vomiting. Seventeen patients developed grade 4 neutropenia and 3 patients grade 4 thrombocytopenia during the course of treatment. Fourteen (46.7%) patients underwent a total of 37 hospitalizations. Common reasons for hospitalizations were: febrile neutropenia (19), pneumonia (6) and thrombocytopenia (3). Sixteen (53.3%) patients never required hospitalization while undergoing treatment. No deaths were attributed to complications related to therapy.Decitabine administered as an outpatient is an effective treatment option for elderly and high risk patients with AML. It has a favorable chemotherapy-related toxicity profile and is associated with a decreased frequency of hospitalizations. Decitabine may facilitate a subsequent allogeneic transplant in eligible patients and should be considered a treatment option for high risk patients with AML. Disclosures:Off Label Use: decitabine in AML.

Oxaliplatin for colorectal cancer: Prevalence of delayed nausea and/or vomiting

e20610 Background: Delayed nausea and vomiting (N&amp;V) have been associated with cisplatin and carboplatin. Its prevalence with third-generation oxaliplatin was examined in patients (pts) receiving oxaliplatin-based regimens. Methods: 64 pts (53% male, 47% female) signed IRB-approved informed consent and were enrolled on day 1 of cycle 1. 53 (83%) pts had colon cancer, and received 85mg/kg of oxaliplatin, while 11 (17%) had rectal cancer, and received 65mg/kg. Age ranged from 29 to 84 years, with 65% between 50 and 69. Data was collected on the first chemotherapy cycle of 24 pts and the first and second cycles of 40 pts, for a total of 104 cycles. Baseline demographic data were collected by chart review and interview. Maximum grade of N&amp;V for each cycle was assessed by the Functional Living Index - Emesis (FLIE). Pts also maintained a daily diary of nausea, vomiting, and anti-emetic usage for 7 days after each infusion. Results: 7 pts (11%) reported a history of motion sickness. History of morning sickness was reported by 13 (43%) of the 30 female pts. All pts received anti-emetics and steroids on day 1 of each cycle. 75% of pts received 5HT3 inhibitors only, 22% received 5HT3 + an oral NK-1 receptor antagonist, and 3% received an NK-1 receptor antagonist alone. Among 40 pts for whom data were collected on both first and second cycles, the occurrence of nausea was the same during cycle 1 and cycle 2: Grade 0 - 60% and 62% respectively; Grade 1 - 20% and 21%, Grade 2 - 20% and 21%. 41% of pts used rescue antiemetics (prochlorperazine, metoclopramide, or lorazepam) in cycle 1 and 43% in cycle 2. Men experienced no nausea 69% of the time, while women had no nausea in 41% of cycles. In 57% of cycles, no nausea was reported. In 88% of cycles there was no reported vomiting. Conclusions: Oxaliplatin-based regimens (65–85 mg/kg) caused minimal nausea and negligible vomiting, with a satisfactory response to 5HT3-inhibitor antiemetics and corticosteroids. [Table: see text] [Table: see text]

Safety and effectiveness of ezetimibe in liver transplant recipients with hypercholesterolemia

Hypercholesterolemia is a common problem among transplant recipients. Despite package-insert warnings about the potential side effects of the use of statins in patients with chronic liver disease, they are often prescribed for liver transplant recipients. Unlike statins, ezetimibe acts through inhibition of enterohepatic recirculation of lipids. We report the effectiveness and safety of ezetimibe among liver transplant recipients because this has been evaluated previously only in kidney and heart transplant patients. A consecutive cohort of 25 liver graft recipients with serum low-density lipoprotein (LDL) levels > 100 mg/dL (2.5 mmol/L) after a mean (+/-standard deviation) of 55 +/- 21 months following liver transplantation received ezetimibe (10 mg orally every day) for at least 6 months. Serum lipid profiles, liver and renal function tests, and dosages and blood levels of the immunosuppression drugs at baseline, 3 months, and 6 months were prospectively collected. The overall mean age was 58 +/- 12 years, and 56% were males. Statin therapy and fibrates were already being used in 32% and 20% of recipients for elevated LDL and/or triglycerides, respectively. The immunosuppression regimen included cyclosporine in 48% of subjects, tacrolimus in 32%, sirolimus in 48%, and mycophenolate mofetil in 44%; only 12% were on oral prednisone with a maximum daily dose of 5 mg. After ezetimibe was started, an 18% reduction in LDL values was observed [at baseline, 147 +/- 35 mg/dL (3.8 +/- 0.9 mmol/L), and at 6 months, 120 +/- 31 mg/dL (3.1 +/- 0.8 mmol/L); P = 0.010]. After 6 months, an additional 32% achieved the target LDL level of <100 mg/dL. None of the remaining variables, including immunosuppression drug levels, varied significantly during ezetimibe therapy. None of the subjects required adjustments in their pharmacological dosages. One discontinued ezetimibe 3 months later because of cost, 2 subjects had minimal nausea, 1 subject had myalgias without a rise in creatine phosphokinase, and 1 subject had a transient elevation (3-5 times) in liver enzymes from baseline with increases in the total and indirect bilirubin levels. In conclusion, among liver transplant recipients, hypercholesterolemia can be effectively treated with ezetimibe with few side effects and no interaction with immunosuppressive regimens.

Hemolytic Uremic Syndrome

A.P., a 42-year-old woman, presented with rectal bleeding to her primary care physician. Endoscopic examination revealed a mass in the anal canal. Biopsy was positive for squamous cell carcinoma. A.P. underwent local excision and was established as stage ii (T2n0m0). After surgery, she received 5-fluorouracil (Fu) 1,000 mg/m by continuous infusion on days 1–4 and on days 29–32, mitomycin-c 10 mg/m days 1 and 29, and radiation therapy (4c500 cgy). minimal nausea was the only side effect. A.P. achieved complete remission. Approximately eight weeks after completing therapy, A.P. presented for an implantable port flush. The nurse noted that A.P. was pale, weak, and short of breath. A complete blood count (cBc) was obtained and revealed a hematocrit of 17.1% (normal range 37%–48%), hemoglobin of 4.9 (normal range 12.3–15.3 g/dl), and platelet count of 50,000 (normal range 150,000–450,000 cells/ml). A physical examination revealed paleness with generalized anasarca. A.P. was afebrile; her blood pressure was 180/100 mm Hg, pulse rate was 72, and respiration was 24. A.P. was admitted to the hospital for further evaluation and possible blood transfusion. Other laboratory results included a serum creatinine 3.5 mg/dl (normal range 0.7–1.4 mg/dl), lactic dehydrogenase (lDH) 342 units/l (normal range 140–280 units/l), and serum haptoglobin < 38 mg/dl (normal range Hemolytic Uremic Syndrome

Evaluation of the otolith function using sinusoidal off-vertical axis rotation in patients with benign paroxysmal positional vertigo

The vestibulo-ocular reflex (VOR) was studied via sinusoidal off-vertical axis rotation (OVAR) to evaluate the otolith function in patients with benign paroxysmal positional vertigo (BPPV). Subjects were sinusoidally rotated with eyes open in complete darkness at frequencies of 0.4 and 0.8 Hz with a maximum angular velocity of 60 degrees s(-1) in earth-vertical axis rotation (EVAR) and OVAR. Twenty-three controls and 24 BPPV patients were investigated. Results showed that VOR gain during OVAR at 0.8 Hz in a 30 degrees nose-up position in BPPV patients was significantly less than the gain during EVAR, whereas the gain was not significantly different between EVAR and OVAR in the controls in each condition. In addition, to examine each type of BPPV, we also investigated whether there were any differences between the patients who suffered from dizziness and those who did not. VOR gain in OVAR of BPPV patients who were suffering from dizziness was significantly less than that of BPPV patients without dizziness. Not only cupulolithiasis or canalolithiasis, but also otolith dysfunction was considered to be the possible origin of BPPV. Because sinusoidal OVAR produced minimal nausea compared to constant velocity OVAR, the stimulation of 0.8 Hz nose-up in sinusoidal OVAR may be used to evaluate otolith function without discomfort for patients.

Comparasion of granisetron and metoclopramide for prevention of nausea and vomiting following total cystectomy and ileal conduit

The objective of this study was to examine the use of granisetron in actual clinical practice and to compare effect of dose of 1 mg granisetron after total cystectomy plus ileal conduit with group of patients which received metoclopramide. Granisetron established total contol of PONV in 93,33% patients. Granisetron is 40% more effective in PONV control than metoclopramide. Only minimal nausea epizodes were observed in early postoperative period in patients who had received low dose of granisetron (1 mg i.v.).

Emetic potential of daily oral etoposide

Chemotherapeutic agents are classified by their degree of emetogenicity. Highly and moderately emetogenic agents require antiemetic prophylaxis for chemotherapy-induced nausea and vomiting. Intravenous etoposide is listed as having low emetic potential. However, oral etoposide is categorized as having moderate emetogenicity. Daily oral etoposide is used in refractory germ cell cancer patients. We prospectively evaluated the emetic potential of oral etoposide in this patient population. Between August 2003 and February 2006, 16 patients with refractory germ cell cancer received single-agent, daily oral etoposide 50 mg/M(2) for 21 consecutive days every 4 weeks. All patients had progressed after cisplatin combination chemotherapy and had received high-dose chemotherapy with carboplatin plus etoposide (intravenously) with peripheral blood stem cell transplant. No patient received prophylactic antiemetics. Patients completed a six-question Multinational Association of Supportive Care in Cancer (MASCC) antiemetic tool during each day of etoposide during the first 21-day course. Nausea intensity and duration were recorded. Number of emetic episodes and any antiemetic medications were recorded. All 16 patients completed the six-question MASCC form. Eleven of 16 had no nausea or vomiting and two other patients had only minimal nausea, despite absence of any prophylactic antiemetics. Only two patients required antiemetic support. Two patients experienced emesis for a single episode. One patient had nausea on days 9-20 with a MASCC rating of 3-6, and one patient had continued mild nausea (MASCC rating 1-3) for all 21 days. Daily oral etoposide has a low probability of producing chemotherapy-induced nausea and/or vomiting and, in our opinion, does not require prophylactic antiemetics.