Changes In Laboratory Values Research Articles

Trends in the Aggressiveness of End-of-Life Care for Advanced Stomach Cancer Patients

PurposeIt is important to balance the appropriateness of active cancer treatments and end-of-life care to improve the quality of life for terminally ill cancer patients. This study describes the treatment patterns and end-of-life care in terminal gastric cancer patients.Materials and MethodsWe retrospectively analyzed the records of 137 patients with advanced gastric cancer receiving chemotherapy and dying between June 1, 2006 and May 31, 2011. We recorded interval between last chemotherapy dose and death; frequency of emergency room visits or admission to the intensive care unit in the last month before death; rate of hospice referral and agreement with written do-not-resuscitate orders; and change in laboratory values in the last three months before death.ResultsDuring the last six months of life, 130 patients (94.9%) received palliative chemotherapy; 86 (62.7%) during the final two months; 41 (29.9%) during the final month. During the final month, 53 patients (38.7%) visited an emergency room more than once; 21 (15.3%) were admitted to the intensive care unit. Hospice referral occurred in 54% (74 patients) of the patients; 93.4% (128 patients) gave written do-not-resuscitate orders. Platelets, aspartate aminotransferase and creatinine changed significantly two weeks before death; total bilirubin, one month before; and C-reactive protein, between four and two weeks before death.ConclusionOur results demonstrated that a significant proportion of gastric cancer patients received palliative chemotherapy to the end of life and the patients who stopped the chemotherapy at least one month before death had a lower rate of intensive care unit admission and longer overall survival than those who sustained aggressive chemotherapy until the last months of their lives.

Efficacy of Short-Term Growth Hormone Treatment in Prepubertal Children with Idiopathic Short Stature

PurposeIt has been reported that daily recombinant human growth hormone (GH) treatment showed beneficial effects on growth in prepubertal children with idiopathic short stature (ISS). The present study aimed to validate the GH (Eutropin®) effect on growth promotion and safety after short-term GH treatment.Materials and MethodsThis study was an open-label, multicenter, interventional study conducted at nine university hospitals in Korea between 2008 and 2009. Thirty six prepubertal children with ISS were enrolled in this study to receive 6-month GH treatment. Yearly growth rate, height standard deviation score (SDS), and adverse events were investigated during treatment.ResultsAfter 26 weeks of GH treatment, the height velocity significantly increased by 6.36±3.36 cm/year (p<0.001). The lower end of one-sided 95% confidence interval was 5.22 cm/year, far greater than the predefined effect size. The gain in height SDS at week 26 was 0.57±0.27 (p<0.0001). Bone age significantly increased after GH treatment, however, bone maturation rate (bone age for chronological age) showed limited advancement. This 26-week GH treatment was effective in increasing serum levels of insulin-like growth factor (IGF)-I and IGF binding protein (IGFBP)-3 from baseline (p<0.0001). Eutropin was well tolerated and there were no withdrawals due to adverse events. No clinically significant changes in laboratory values were observed.ConclusionThis 6-month daily GH treatment in children with ISS demonstrated increased height velocity, improved height SDS, and increased IGF-I and IGFBP-3 levels with a favorable safety profile.

Laboratory Testing in Monitoring the Effects of Brown Recluse Spider Bites

Brown recluse spiders are endemic to the central United States and are highly venomous. Although most brown recluse spider bites do not cause dangerous wounds or systemic symptoms, severe cases can occur. Changes in laboratory values may include hemolysis, thrombocytopenia, coagulopathy, and altered chemistry and urinalysis results. Neutrophil involvement in wound progression and white blood cell changes can be observed. If blood products are indicated, fresh frozen plasma and cryoprecipitate should be avoided. There is no single clinical lab test that can be used to diagnose a brown recluse spider bite, but laboratory involvement in monitoring progression and treatment may be significant. * ELISA : enzyme-linked immunosorbent assay; CBC : complete blood count; DAT : direct antiglobulin test; ALT : alanine transaminase; AST : aspartate aminotransferase; LDH : lactate dehydrogenase; CK : creatine kinase; DIC : disseminated intravascular coagulation; PT : prothrombin time; PTT : partial thromboplastin time; ESR : erythrocyte sedimentation rate; G6PD : glucose-6 phosphate dehydrogenase

The effect of a supplement of chromium (picolinate) on the level of blood glucose, insulin activity and changes in laboratory evaluation of the ejaculate of breeding boars

The experiment was based on feeding the organic form of chromium (picolinate) and the assessment of its effect on the level of blood glucose, insulin activity and changes in the laboratory values of the ejaculate (sperm motility, ejaculate volume, sperm concentration and per cent of pathological sperm) in breeding boars. The experiment involved 40 boars divided into two equal groups. Boars of the experimental group (n = 21) received 181.81 μg of chromium per kg of feed ration (FR) administered perorally, in the control group (n = 19) chromium intake was not increased. The chromium supplement significantly (P &lt; 0.05) increased cell absorption of blood glucose in the experimental group of boars as against the control group. There was no difference in insulin activity between the two groups. Changes in laboratory values of the ejaculate were evaluated and no significant differences were discovered in any of the parameters. During the experiment the sperm concentration and motility were absolutely the same in boars of both groups; it can therefore be concluded that increasing the level of chromium in the feed ration of boars of the experimental group had no direct effect on these parameters. It was the same in the case of the ejaculate volume which gradually decreased between periods 1 and 4, in boars receiving chromium by 12.8 % and in the control group by 8.1 %. The beneficial effect of chromium was seen in the reduced count of pathological sperm in boars in periods 3 and 4 of tests as against boars of the control group. In spite of the considerable 26.3 % difference between the groups this decrease was not statistically significant. Data evaluation revealed a significant correlation (P &lt; 0.01) between the number of samplings per boar and sperm concentration. A correlation (P &lt; 0.05) was also detected between the ejaculate volume and sperm concentration

Low-dose paroxetine 7.5 mg for menopausal vasomotor symptoms

The efficacy and safety of low-dose paroxetine 7.5 mg for the treatment of menopausal vasomotor symptoms were evaluated in two multicenter, double-blind, placebo-controlled, phase 3 studies of 12 and 24 weeks' duration. Postmenopausal women were randomly assigned 1:1 to receive paroxetine 7.5 mg or placebo once daily. The four primary efficacy endpoints included mean changes in the frequency and severity of moderate to severe vasomotor symptoms on weeks 4 and 12; an additional endpoint was persistence of treatment benefit on week 24. Five hundred ninety-one participants were randomly assigned to treatment with paroxetine 7.5 mg, and 593 participants were randomly assigned to treatment with placebo. All primary endpoints were met in the 24-week study; three of four primary endpoints were met in the 12-week study. In both studies, paroxetine 7.5 mg significantly reduced the mean weekly vasomotor symptom frequency compared with placebo on week 4 (P < 0.0001 for both studies) and week 12 (P = 0.0090, 12-wk study; P = 0.0001, 24-wk study). Mean weekly reduction in vasomotor symptom severity was significantly greater for paroxetine 7.5 mg than for placebo on week 4 (P = 0.0048) in the 12-week study and on week 4 (P = 0.0452) and week 12 (P = 0.0114) in the 24-week study. Persistence of treatment benefit was demonstrated in the 24-week study. Most treatment-emergent adverse events were mild or moderate in severity. No clinically significant changes in laboratory values or vital signs were noted, and no short-term discontinuation of symptoms followed treatment cessation. Paroxetine 7.5 mg is well-tolerated, is effective in reducing the frequency and severity of menopausal vasomotor symptoms, and demonstrates persistence of treatment benefit through 24 weeks of treatment.

Dolutegravir does not affect methadone pharmacokinetics in opioid-dependent, HIV-seronegative subjects

BackgroundDolutegravir (DTG) is an investigational integrase inhibitor for treatment of HIV infection. As intravenous drug use is a common risk factor for HIV, this study evaluated the effect of DTG on the pharmacokinetics (PK) of methadone. MethodsThis was an open-label, 2-period study in adult, opioid-dependent, HIV-seronegative subjects. Subjects received their current individual methadone doses once daily for 3 days (Period 1) followed by DTG 50mg twice daily (BID) for 5 days while continuing their stable methadone therapy (Period 2). Serial PK samples for R- and S-methadone were collected after each Period. Pharmacodynamic (PD) measures and safety assessments were obtained throughout the study. Non-compartmental PK analysis was performed, and geometric least-squares mean ratios and 90% confidence intervals were generated. ResultsPlasma exposures of total, R-, and S-methadone were not affected by co-administration of DTG. Mean ratios for AUC were 0.98, 0.95, and 1.01 for total, R-, and S-methadone, respectively, alone compared with in combination with DTG. No statistically significant differences were noted between the 2 treatment periods in methadone PD measures. The combination of DTG and methadone was well tolerated. No deaths, serious adverse events, or grade 3/4 adverse events occurred. No clinically significant changes in laboratory values, vital signs, or electrocardiograms were observed. ConclusionCo-administration of methadone with repeat doses of DTG 50mg BID had no effect on total, R-, and S-methadone PK or on methadone-induced PD markers. No dose adjustment in methadone is required when given in combination with DTG.

Pharmacokinetic Properties of Once-Daily Oral Low-Dose Mesylate Salt of Paroxetine (LDMP 7.5 mg) Following Single and Multiple Doses in Healthy Postmenopausal Women

BackgroundLow-dose mesylate salt of paroxetine (LDMP 7.5 mg) is being investigated for the treatment of vasomotor symptoms associated with menopause. ObjectiveThis Phase I, open-label, single- and multiple-dose study evaluated the pharmacokinetic properties, safety and tolerability of LDMP in postmenopausal, nonsmoking women aged ≥40 years. MethodsAfter a 3-week screening period, subjects received LDMP 7.5-mg capsules as a single dose on day 1 and then as multiple doses (once daily for 14 days) on Days 6–19. Blood samples were collected predose and up to 120 hours postdose on day 1 (single-dose pharmacokinetic profile), at predose (after 12 doses) on day 18, and at predose and up to 24 hours postdose on day 19 (multiple-dose pharmacokinetic profile). Capsules were taken with 240 mL of water while subjects were fasted. Safety was evaluated throughout the study. ResultsTwenty-four women (mean age, 56 years) completed the study. On day 1, median Tmax was ~6 hours, and mean t1/2 was 17.30 hours. Mean plasma concentrations attained predose on days 18 and 19 (days 13 and 14 of multiple dosing) and at 24 hours postdose (day 20) were similar, suggesting that steady state was achieved by day 13 of multiple dosing after 12 daily doses. Mean AUC0–24 h at steady state (day 14 of multiple dosing) was ~3-fold greater than AUC0–∞ on day 1, indicating nonlinear pharmacokinetics. Mean Cmax on day 14 of multiple dosing was ~5-fold greater than that attained on day 1, and the accumulation index (AUCday 19/AUCday 1) at steady state was 9.71. Fluctuation index (calculated as [(Cmax – Cmin)/Cavg ss] × 100) was 75.8%. Most subjects (23/24 [95.8%]) experienced at least 1 treatment-emergent adverse event (AE); however, most AEs (67 events in 22/24 subjects [91.7%]) were mild, and the remainder were moderate. Seventeen subjects experienced 33 AEs that were deemed possibly or probably related to LDMP. No serious AEs were reported, and no clinically meaningful changes in laboratory values, vital signs, or ECGs were observed. ConclusionsOn multiple dosing, LDMP exhibited nonlinear pharmacokinetics and was well tolerated in these healthy postmenopausal women; the extent of accumulation was consistent with data from the published literature. ClinicalTrials.gov identifier: NCT01829919.

LB0003 Tocilizumab (TCZ) monotherapy is superior to adalimumab (ADA) monotherapy in reducing disease activity in patients with rheumatoid arthritis (RA): 24-week data from the phase 4 adacta trial

BackgroundApproximately 1/3 of RA patients (pts) on biologics receive them as monotherapy (without other DMARDs) [1,2]. TCZ, an inhibitor of IL-6 receptor signalling, has been studied as monotherapy in 3...

Efficacy and safety of adjunctive perampanel for the treatment of refractory partial seizures: A pooled analysis of three phase III studies

Three phase III studies (304 [ClinicalTrials.gov identifier: NCT00699972], 305 [NCT00699582], 306 [NCT00700310]) evaluated perampanel, an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, as adjunctive therapy for refractory partial seizures. We report post hoc analyses of pooled study data by randomized dose. Patients with partial seizures despite receiving 1-3 antiepileptic drugs were randomized to once-daily placebo, perampanel 8 or 12 mg (studies 304, 305), or placebo, perampanel 2, 4, or 8 mg (study 306). Studies included a 6-week baseline period and double-blind treatment phase (6-week titration; 13-week maintenance). Primary end points were median change in partial seizure frequency (baseline vs. double-blind phase) and percentage of patients achieving ≥ 50% reduction in seizure frequency (baseline vs. maintenance). Here, these end points, together with secondary, exploratory, and safety end points, were assessed using pooled study data. The pooled intent-to-treat analysis set (randomized, treated patients with any seizure data) included 1,478 patients. Median changes in partial seizure frequency were greater with perampanel than placebo (perampanel 4 mg, -23.3%; 8 mg, -28.8%; 12 mg, -27.2%; placebo, -12.8%; p < 0.01, each dose vs. placebo), as were 50% responder rates (perampanel 4 mg, 28.5%; 8 mg, 35.3%; 12 mg, 35.0%; placebo, 19.3%; p < 0.05, each dose vs. placebo). In addition, median changes in complex partial plus secondary generalized seizure frequency were also greater with perampanel than placebo (perampanel 4 mg, -31.2%; 8 mg, -35.6%; 12 mg, -28.6%; placebo, -13.9%). Perampanel was generally well tolerated. The most frequent treatment-emergent adverse events (TEAEs) were dizziness, somnolence, and headache. Most TEAEs were mild/moderate; relatively few patients experienced severe TEAEs (placebo, 5.4%; perampanel, 8.9%) or serious TEAEs (placebo, 5.0%; perampanel, 5.5%). There were no deaths and no clinically important mean changes in laboratory values, electrocardiography (ECG) findings, or vital signs. Perampanel reduced partial seizure frequency and improved responder rates compared with placebo, with an acceptable tolerability profile.

Dialysate Calcium Concentration and Mineral Metabolism in Long and Long-Frequent Hemodialysis: A Systematic Review and Meta-analysis for a Canadian Society of Nephrology Clinical Practice Guideline

Patients treated with conventional hemodialysis (HD) develop disorders of mineral metabolism that are associated with increased morbidity and mortality. More frequent and longer HD has been associated with improvement in hyperphosphatemia that may improve outcomes. Systematic review and meta-analysis to inform the clinical practice guideline on intensive dialysis for the Canadian Society of Nephrology. Adult patients receiving outpatient long (≥5.5 hours/session; 3-4 times per week) or long-frequent (≥5.5 hours/session, ≥5 sessions per week) HD. We included clinical trials, cohort studies, case series, case reports, and systematic reviews. Dialysate calcium concentration ≥1.5 mmol/L and/or phosphate additive. Fragility fracture, peripheral arterial and coronary artery disease, calcific uremic arteriolopathy, mortality, intradialytic hypotension, parathyroidectomy, extraosseous calcification, markers of mineral metabolism, diet liberalization, phosphate-binder use, and muscle mass. 21 studies were identified: 2 randomized controlled trials, 2 reanalyses of data from the randomized controlled trials, and 17 observational studies. Dialysate calcium concentration ≥1.5 mmol/L for patients treated with long and long-frequent HD prevents an increase in parathyroid hormone levels and a decline in bone mineral density without causing harm. Both long and long-frequent HD were associated with a reduction in serum phosphate level of 0.42-0.45 mmol/L and a reduction in phosphate-binder use. There was no direct evidence to support the use of a dialysate phosphate additive. Almost all the available information is related to changes in laboratory values and surrogate outcomes. Dialysate calcium concentration ≥1.5 mmol/L for most patients treated with long and long-frequent dialysis prevents an increase in parathyroid hormone levels and decline in bone mineral density without increased risk of calcification. It seems prudent to add phosphate to the dialysate for patients with a low predialysis phosphate level or very low postdialysis phosphate level until more evidence becomes available.

Activity observed in a phase I dose escalation trial of the hypoxia-activated, NO prodrug, RRx001.

241 Background: RRx-001, the first member of a new class of anticancer compounds sourced from the defense industry, is a hypoxia-selective, nitrite reductase-activated prodrug of nitric oxide (NO). The active metabolites selectively enhance oxidative and nitrosative stress in cancer cells through glutathione depletion, ROS formation, and the generation of high local concentrations of NO. The objectives of this Phase 1 dose-escalation trial were to investigate safety, dose-limiting toxicities (DLTs), pharmacodynamics and pharmacokinetics (PK) of RRx-001. Methods: Eligible patients had advanced solid tumor malignancies; ECOG PS 0-2; adequate bone marrow function. In a 3+3 escalation design, RRx-001 was administered intravenously (IV) over 2-3 hours once weekly for 8 weeks to patients with advanced cancer in successive dose-escalating cohorts. PK was collected on days 1 and 50, and tumor blood flow, assessed by CEUS or DCE/DWI-MRI, was performed on days 1 and 8. Tumor response was determined every 8 weeks. Results: To date 12 patients have been dosed across 3 successive cohorts (10, 16.7, and 24.6 mg/m2). Tumor types included pancreas (3), colorectal (5), head and neck (2), melanoma (1), and cholangiocarcinoma (1). No DLTs or treatment-associated SAEs were observed. Transient infusion site pain was reported in 10/12 patients, grade 1 (9/10) or grade 2 (1/10), generally managed by lengthening the infusion duration and using peripheral venous access. No relevant treatment-related changes in laboratory values were observed. Seven patients were evaluable for response, with 1 partial response (parotid tumor). Three patients had stable disease ≥ 2 months (2 pancreas, 1 colorectal with treatment duration 10+ months, exceeding the response to his previous chemo regimen). One pancreas patient with an increase in tumor size due to treatment-related central necrosis was diagnosed with pseudoprogression and remained on study for 4 months. Conclusions: RRx-001, an anticancer agent with a novel structure and mechanism of action, is well tolerated with mild infusion-site pain. PK and PD data will be presented. Escalation is ongoing, but preliminary evidence of anti-tumor activity is promising. Clinical trial information: NCT01359982.

Baseline Blood Work Before Initiation of Chemotherapy: What Is Safe in the Real World?

This is an observational study of patterns of practice of the timing of baseline blood work (BBW) before chemotherapy initiation. The primary objective was to evaluate the incidence of significant changes in laboratory values within 6 weeks before therapy. All consecutive patients receiving chemotherapy within a 6-month period were analyzed retrospectively. Time interval between date of chemotherapy initiation and nearest blood work was calculated. Data from patients with one or more sets of values within 6 weeks were used to evaluate dosing changes. Changes in laboratory values collected closest to the date of chemotherapy and values collected before that but within 6 weeks were graded according to the National Cancer Institute's Common Toxicity Criteria. A change of ≥1 grade was considered clinically meaningful. Five hundred ninety-two patients were included. Median interval between BBW and initiation of chemotherapy was 4 days. Three hundred thirty-five patients had two or more sets of laboratory tests within the 6-week period, 33% of patients had a meaningful change in one or more values. The majority of changes occurred in hemoglobin (22%), ALT (14%), WBC (11%) and AST(10%), yet only 66% of patients had liver function tests as part of the BBW. Adherence to the institutional recommendation of BBW within 6 weeks was high. Baseline laboratory tests performed within 7 days of chemotherapy initiation would have detected nearly all significant changes; therefore, we suggest that this interval be tested in future randomized trials.

Diffusion-weighted MR imaging; the importance of ADC and perfusion values in the differential diagnosis of pancreatic adenocarcinoma and mass forming pancreatitis

Despite the increasing diagnostic accuracy of cross sectional imaging modalities, the correct differentiation between pancreatic adenocarcinoma and mass forming pancreatitis has remained a challenge. Based on their 2 and ½ -year experience, the aim of the authors was to assess the clinical utility of diffusion-weighted magnetic resonance imaging in the diagnosis and discernment of pancreatic adenocarcinoma and mass forming pancreatitis. 3 b-values diffusion-weighted magnetic resonance examinations were performed in 19 patients suffering from adenocarcinoma and in 8 patients with pancreatitis. 12 healthy patients were examined as reference. Apparent diffusion coefficient and perfusion values were calculated. Malignancy was verified by pathology in all cases. An inflammatory disease was diagnosed on the basis of previous medical history, changes in laboratory values, follow-up computer tomographic examinations and improvement in the patients' condition. Comparison of the apparent diffusion coefficient and perfusion values revealed significant differences between healthy pancreatic tissues and those affected by inflammation or tumor. The highest apparent diffusion coefficient and perfusion values were detected in the normal pancreas. Mass forming pancreatitis had diminished the apparent diffusion coefficient and perfusion values, whereas these values were the lowest in tumorous tissues. In agreement with literature data, the authors conclude that diffusion-weighted magnetic resonance imaging is a promising differential-diagnostic imaging tool in the distinction of circumscribed pancreatic lesions.

Pharmacokinetics and safety of Intragam 10 NF, the next generation 10% liquid intravenous immunoglobulin, in patients with primary antibody deficiencies

Intragam® 10 NF is the next generation 10% intravenous immunoglobulin with three pathogen reduction steps and a noncarbohydrate stabiliser. This open label, cross-over study in patients with primary immunodeficiency was designed to evaluate whether Intragam 10 NF differed in its pharmacokinetics (PK) compared with Intragam P and to assess Intragam 10 NF safety and tolerability. Nineteen primary immunodeficiency patients were administered one cycle of their existing Intragam P dose (0.2-0.8 g/kg 3-4 weekly), followed by seven cycles of Intragam 10 NF administered at the same dosing schedule as Intragam P. The primary objective was to compare serum immunoglobulin G (IgG) trough levels. Secondary endpoints were PK variables, safety and tolerability. There was no significant within-patient difference in the average trough immunoglobulin G concentration between Intragam P and Intragam 10 NF (8.76 g/L, 8.55 g/L respectively) (geometrical mean ratio 1.034; 95% confidence interval 0.996-1.073; P = 0.079). Mean PK parameters for both products were similar, with all 95% confidence interval encompassing 1.0 except for time to maximum concentration. Time to maximum concentration occurred earlier with Intragam 10 NF compared with Intragam P, with a shorter infusion time (mean 1.75 h vs 2.52 h respectively; P < 0.05). Headache was the most frequent treatment-related event following both products. There were no study withdrawals, deaths, or notable changes in laboratory values or vital signs. Intragam 10 NF was well tolerated and exhibited similar PK to Intragam P, with the advantage of a 45 min shorter infusion time.

Percutaneous Cryoablation of Lung Tumors: Feasibility and Safety

PurposeTo evaluate the safety and feasibility of cryoablation for lung tumors as well as the incidence of, and risk factors for, complications. Materials and MethodsThis study included 193 cryoablation sessions for 396 lung tumors in 117 consecutive patients. Univariate and multivariate analyses were performed to assess risk factors for common complications. Changes in laboratory values were analyzed the day after cryoablation. ResultsPneumothorax, pleural effusion, and hemoptysis occurred after 119 (61.7%), 136 (70.5%), and 71 (36.8%) sessions, respectively. Phrenic nerve palsy, frostbite, and empyema occurred after one session each (0.52%). Proximal tumor implantation was observed in one of 471 punctures (0.20%). Of 119 sessions with pneumothorax, 21 (17.6%) required chest tube insertion and two (1.7%) required pleurodesis. Delayed and recurrent pneumothorax occurred in 15 of 193 sessions each (7.8%). A greater number of cryoprobes was a significant (P = .001) predictor of pneumothorax. Male sex (P = .047) and no history of ipsilateral surgery (P = .012) were predictors for the need for chest tube insertion, and no history of ipsilateral surgery (P = .021) was a predictor for delayed/recurrent pneumothorax. Greater number of cryoprobes (P = .001) and no history of ipsilateral surgery (P = .004) were predictors for pleural effusion. Greater number of cryoprobes (P < .001) and younger age (P = .034) were predictors for hemoptysis. Mean changes in white blood cell count, platelet count, hemoglobin level, and C-reactive protein level were 2,418/μL ± 2,260 (P < .001), −2.0 × 104/μL ± 3.2 (P < .001), −0.77 mg/dL ± 0.89 (P < .001), and 3.0 mg/dL ± 2.9 (P < .001), respectively. ConclusionsPercutaneous cryoablation could be performed minimally invasively with acceptable rates of complications.

Intra-anal Iferanserin 10 mg BID for Hemorrhoid Disease: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial

BackgroundDespite the prevalence of internal hemorrhoid disease (HD), there are few pharmacologic options. Iferanserin, a selective serotonin receptor antagonist, is being studied for use in the treatment of HD. ObjectiveThis Phase IIb study evaluated the efficacy and tolerability of 10-mg twice-daily iferanserin intra-anal ointment for the cessation of bleeding and other symptoms associated with internal HD. MethodsThis randomized, double-blind, placebo-controlled study was conducted at 5 sites in Germany. Outpatients with Goligher grade I, II, and/or III hemorrhoids and bleeding were randomly assigned to receive iferanserin ointment 10 mg or inactive vehicle (placebo) BID for 14 days. During treatment, patients rated the severity of HD symptoms daily on a 10-point scale using a diary form. At enrollment and study end, physicians recorded the frequency and intensity of HD symptoms, adverse events, and results from blood and urine analyses on clinical-report forms. ResultsOf the 121 patients enrolled in the study, 118 were evaluable for tolerability and 111 for efficacy. The mean age of the tolerability population was 52.7 years, 78.9% were male, and all were white. The 2 groups had similar HD symptoms at baseline, but overall, patients in the placebo group had numerically higher grades of HD than did patients in the iferanserin group. Compared with placebo, iferanserin was associated with significantly lower patient-reported severity ratings of daily bleeding and itching, beginning at day 1 for bleeding and at day 2 for itching (P < 0.05), but not with reduced ratings for severity of other HD symptoms, including pain, tenderness, difficulty with defecation, fullness, throbbing, and gas. In the physician assessments, iferanserin was associated with significantly reduced bleeding frequency by day 14 compared with placebo (P < 0.05). Adverse events were mild and infrequent, with no significant differences in prevalences between the 2 treatment groups and no clinically significant changes in laboratory values in any patient. ConclusionCompared with placebo, intra-anal iferanserin was associated with significantly reduced patient-reported severity of bleeding and itching and physician-assessed bleeding frequency in these patients presenting with grade I, II, and/or III internal hemorrhoids and bleeding at 5 sites in Germany. ClinicalTrials.gov identifier: 01483833.

Changes in laboratory values you Should know for nutritional management

Changes in laboratory values you Should know for nutritional management

Granisetron Transdermal Patch for Treatment of Nausea in Patients Undergoing Cisplatin Based Chemotherapy for Cervical Cancer

Objective: The purpose of this study was to define the incidence of chemotherapy-induced nausea and vomiting (CINV) in newly diagnosed cervical cancer patients receiving cisplatin and radiation treatment; and to determine if the granisetron transdermal patch (Sancuso?) would be appropriate to recommend as part of standard antiemetic regimen for the cisplatin radiation chemotherapy order set. Methods: This is a retrospective case-controlled study of cervical cancer patients receiving cisplatin chemotherapy with radiation (cisXRT); comparing patients receiving the granisetron transdermal patch to matched patients receiving oral 5HT3 blockers. All patients prescribed cisXRT between September 15th 2008 and November 30, 2011 were identified using pharmacy dispensing records. Patients were included if they received at least a partial dose of cisXRT and Sancuso? patch as standard antiemetic prophylaxis prior to cisXRT for cervical cancer treatment. Exclusion criteria included concomitant investigational agents, biotherapy and/or chemotherapy agents; prior chemotherapy; or incomplete or restricted medical records. Patients will be matched based on age. Patients were matched 3:1 (oral:patch). A total of 404 patients that received and completed cisXRT were identified utilizing an existing de-identified database from previous study were reviewed to evaluate parameters of interest. Results: A total of 285 patients’ medication records were reviewed for Sancuso? use, and 47 were identified. Of these 47 charts only five patient cases met eligibility criteria to be included in the study. All five patients that received the granisetron patch had at least three known risk factors for nausea. The nausea/vomiting in these patients did not worsen after receiving the Sancuso? patch, and four out of five had subjective improvement. CINV was unrelated to changes in laboratory values or incidence of other toxicity and was not dose-related. Conclusions: While no definitive conclusions could be drawn from this retrospective analysis, the limited data suggests that patients’ nausea and vomiting did not worsen after receiving the Sancuso? patch, and four out of five patients had subjective improvement. The challenges met and limitations identified justify the need for a prospective study that is now underway to control other contributing variables and evaluate overall efficacy of the granisetron patch for controlling CINV in patients receiving cisplatin plus radiation.

A Comparison of Active Surveillance Programs Including a Spontaneous Reporting Model for Phamacovigilance of Adverse Drug Events in a Hospital

Background/AimsSpontaneous reporting systems have several weak points, such as low reporting rates and insufficient clinical information. Active surveillance programs, such as ward rounds and a clinical data repository (CDR), may supplement the weak points of such systems. We developed active surveillance programs and compared them with existing spontaneous reporting.MethodsWe collected adverse drug event (ADE) cases, which comprised 1,055 cases of spontaneous reporting, 309 reported by ward rounds, and 229 found using a CDR. The clinical features and causative drugs were evaluated.ResultsActive surveillance programs detected additional serious ADEs compared to those of spontaneous reporting programs. The ADEs identified by CDR (22.9%) were more likely to be classified as "serious" than those reported spontaneously (5.2%) or identified during ward rounds (10.3%). Causative drugs also differed. Opioids, antibiotics, and contrast media were the most common drugs causing ADEs in the spontaneous reporting system, whereas the active surveillance programs identified antibiotics as the most common causative drug. Clinical features also differed. ADEs with gastrointestinal manifestations were reported most frequently by spontaneous reporting programs. ADEs reported from active surveillance more reliably identified events associated with changes in laboratory values, such as hepatobiliary toxicity, hematologic manifestations, and nephrologic manifestations, compared with spontaneous reporting programs.ConclusionsOur findings suggest that active surveillance programs can supplement spontaneous reporting systems in hospitals. ADEs related to laboratory abnormalities were monitored more closely by active surveillance programs and may be useful for identification of serious ADEs.

Review of Vasopressor Therapy in the Setting of Vasodilatory Shock

Appropriate selection and utilization of vasopressor therapy are important in the treatment of vasodilatory shock, because inappropriate use can result in increased morbidity and mortality. Vasopressors are differentiated on the basis of their receptor activity, as well as their pharmacokinetic and pharmacodynamic properties. Understanding the pathophysiology of receptor responses in shock, dose-dependent receptor activity variations, and unique patient-specific factors that alter response, all assist the health care provider in selecting the appropriate agent for each patient. Treatment is further individualized on the basis of clinical response and medication titration, as well as laboratory value changes. The intent of this review is to discuss relevant management issues associated with vasopressor use in the emergency department.