Audit of warfarin reversal using a new Octaplex reduced dose protocol

IntroductionProthrombin Complex Concentrate (PCC) is increasingly used for the emergency reversal of the effects of Vitamin K antagonists due to the increased use of the latter. There is no consensus on dosage protocols for its use. There is evidence that small fixed doses are effective. We report the result of the use of a simple three dose level protocol i.e. 2000 IU for CNS bleeds, 1500 IU for other bleeds and 1000 IU for non bleeders.MethodsData was prospectively collected over a 6 month period on all patients receiving PCC (Octaplex). These included clinical indication, dose given, INR test results, delay in treatment, and patients' demographics.ResultsThe protocol was followed in only 40%; 24% were given a larger dose and 35% a smaller dose than we recommended. Despite this the INR was corrected (≤1.5) in 56 (83.6%) out of the 67 patients studied. The average delay in getting INR results was 1 hour 14 minutes and delay between releasing the PCC from blood bank to infusion was 3 hours.ConclusionA simple three level low fixed dose protocol is cost effective in reversing the majority of patients' anticoagulation. Delay in initiating treatment for the reversal of VKA and adherence to protocols remained problematic.     

Standard warfarin dose in a patient with the CYP2C9*3/*3 genotype leads to hematuria

BackgroundPatients with certain CYP2C9 genetic variants have increased sensitivity to warfarin and are at increased risk of over-coagulation with standard warfarin dose. We report over-anticoagulation and hematuria manifest as a slow increase in the international normalized ratio (INR) due to warfarin treatment in a patient with the CYP2C9*3/*3 allele.CaseA 58-y-old man with paroxysmal atrial fibrillation received a standard warfarin dose of 2.0 mg/day. Because INR was 2.00 one week after treatment initiation, he was discharged from the hospital. One month later, hematuria was present and INR had increased to 7.26. Although in normal cases (R)-warfarin plasma concentrations are higher than (S)-warfarin, this patient had the opposite warfarin enantiomer plasma concentration profile.ConclusionsIncreased anticoagulation was due to an increased concentration of (S)-warfarin, the more active warfarin enantiomer. INR response to warfarin in this CYP2C9*3/*3 patient was slow. The later INR response appears to be strongly affected by CYP2C9 variants. He also had the VKORC1 ?1639G > A AA genotype, requiring a lower warfarin dose. In this case, increased risk of bleeding could have been identified by prospective genotyping of CYP2C9 and VKORC1 prior to initiating warfarin therapy.     

A randomised, double-blind, multi-centre trial comparing vasopressin and adrenaline in patients with cardiac arrest presenting to or in the Emergency Department

ObjectiveTo compare vasopressin and adrenaline in the treatment of patients with cardiac arrest presenting to or in the Emergency Department (ED).DesignA randomised, double-blind, multi-centre, parallel-design clinical trial in four adult hospitals.MethodEligible cardiac arrest patients (confirmed by the absence of pulse, unresponsiveness and apnea) aged >16 (aged > 21 for one hospital) were randomly assigned to intravenous adrenaline (1 mg) or vasopressin (40 IU) at ED. Patients with traumatic cardiac arrest or contraindication for cardiopulmonary resuscitation (CPR) were excluded. Patients received additional open label doses of adrenaline as per current guidelines. Primary outcome was survival to hospital discharge (defined as participant discharged alive or survival to 30 days post-arrest).Main resultsThe study recruited 727 participants (adrenaline = 353; vasopressin = 374). Baseline characteristics of the two groups were comparable. Eight participants (2.3%) from adrenaline and 11 (2.9%) from vasopressin group survived to hospital discharge with no significant difference between groups (p = 0.27, RR = 1.72, 95% CI = 0.65–4.51). After adjustment for race, medical history, bystander CPR and prior adrenaline given, more participants survived to hospital admission with vasopressin (22.2%) than with adrenaline (16.7%) (p = 0.05, RR = 1.43, 95% CI = 1.02–2.04). Sub-group analysis suggested improved outcomes for vasopressin in participants with prolonged arrest times.ConclusionsCombination of vasopressin and adrenaline did not improve long term survival but seemed to improve survival to admission in patients with prolonged cardiac arrest. Further studies on the effect of vasopressin combined with therapeutic hypothermia on patients with prolonged cardiac arrest are needed.     

Drug interaction of (S)-warfarin, and not (R)-warfarin, with itraconazole in a hematopoietic stem cell transplant recipient

BackgroundItraconazole is a potent inhibitor of CYP3A4 and P-glycoprotein, but not CYP2C9. Herein, we report a case study in which the plasma concentration of the CYP2C9 substrate (S)-warfarin, and not the CYP3A4 substrate (R)-warfarin, increased with itraconazole coadministration.CaseA 67-y-old man received an allogenic bone marrow transplant for acute lymphoid leukemia. He was taking oral itraconazole (200 mg/day) and was started on a warfarin dose of 2.0 mg/day. The plasma concentrations of (S)- and (R)-warfarin 3 days after starting warfarin administration were 216 and 556 ng/mL, respectively (INR 0.98), and after 10 days, the concentrations were 763 and 545 ng/mL, respectively (INR 2.43). On day 11 after withdrawal of itraconazole, the concentrations of (S)- and (R)-warfarin were 341 and 605 ng/mL, respectively (INR 1.38). The concentration of (R)-warfarin was not affected by itraconazole; however, the final (S)-warfarin concentration had increased 7.3-fold. The (S)-warfarin/(S)-7-hydroxywarfarin ratio decreased to 2.45 from 8.40 after discontinuation of itraconazole. The permeability of warfarin enantiomers across Caco-2 cells was not influenced by itraconazole and showed no difference between enantiomers.ConclusionsCareful INR monitoring is necessary for warfarin co-administration with itraconazole. Further examination is necessary to elucidate mechanisms of the interaction between warfarin and itraconazole.     

Performance characteristics of a new Immulite(®) 2000 system erythropoietin assay

BackgroundSerum erythropoietin (EPO) measurements are useful for diagnostic evaluations of anemia, polycythemia, and other erythroid disorders.MethodsWe evaluated a new formulation of the chemiluminescent immunoassay for EPO on the Immulite 2000 analyzer (Siemens Healthcare Diagnostics) for limit of blank (LoB), imprecision, linearity, interference, comparison to another commercially available assay, reference interval, and cross-reactivity with 2 recombinant EPO preparations.ResultsThe LoB was 0.23 IU/l. Total imprecision ranged from 4.2 to 12.1%. The assay was linear from 0 to 678 IU/l. Hemoglobin caused negative interference at concentrations > 17.4 g/l. Deming regression from the method comparison study gave a slope of 1.00 ± 0.04, an intercept of 3.9 ± 12.7, and a S_y/x of 44.9 (r = 0.98). The non-parametric reference interval was 3.3 to 23.4 IU/l. Epoetin alfa at a1:2000 dilution gave mean results of 541 IU/l and 650 IU/l for Immulite 2000 and Access 2, respectively. Darbopoetin alfa at a 1:2000 dilution gave mean results of 337 IU/l and 579 IU/l for the Immulite 2000 and Access 2, respectively, indicating the 2 assays have substantially different cross-reactivities with recombinant EPO preparations.ConclusionsThe new Immulite 2000 EPO assay shows acceptable performance and is suitable for routine clinical use.     

Functional sensitivity of seven automated thyroid stimulating hormone immunoassays

BackgroundSerum thyroid stimulating hormone (TSH) measurements are useful for detecting clinical and subclinical primary hypo- and hyperthyroidism in ambulatory patients. For diagnosis of hyperthyroidism, the functional sensitivity (FS) is an important performance criterion, and current guidelines recommend an FS of ≤ 0.02 m IU/l for “third” generation performance.MethodsWe evaluated TSH FS for the Access 2, Advia Centaur, Architect i2000, Dimension ExL Modular Analytics E170, Immulite 2000 and Dimension Vista 1500 automated immunoassays using serum pools tested over a 6 week period using 2 reagent lots and 2 calibrations. FS was determined by fitting a power function to the imprecision data using KaleidaGraph software.ResultsThe FS (m IU/l) for Access 2, ADVIA Centaur, ARCHITECT i2000, Dimension ExL, Modular Analytics E170, Immulite 2000, and Dimension Vista 1500 systems were determined to be 0.039, 0.006, 0.007, 0.003, 0.008, 0.003, and 0.003, respectively. The lowest and next to lowest pools had overall mean TSH concentrations of 0.012 m IU/l and 0.020 m IU/l, respectively and a range of concentrations of 0.005 to 0.022 m IU/l and 0.007 to 0.077 m IU/l, respectively.ConclusionsAll assays showed excellent performance in FS consistent with a “third” generation claim except for the Access 2 system. Further harmonization of TSH immunoassays is required, especially at lower concentrations.     

Lack of association between paraoxonase 1 Q192R polymorphism and multiple sclerosis in relapse phase: A case-control study

ObjectivesThe aim of this study was to estimate the serum activity of paraoxonase 1(PON1) and assess the distribution of PON1 polymorphisms in MS patients in the relapse phase.Design and methodsPON1 and arylesterase (ARE) serum activities were measured in two equal groups (each group 63 cases) of relapsing–remitting MS patients and healthy individuals.ResultsMean values for serum PON1 and ARE activities were 90.3 ± 63.4 and 182.1 ± 128.7 IU/L for patients and 99.9 ± 73.3 and 190.8 ± 150.3 IU/L for controls. Those values were not statistically significant (p = 0.242 and p = 0.378), respectively. Comparing genotype distributions and allele frequencies in both groups for PON1 Q192R and PON L55M polymorphisms did not show any statistical difference.ConclusionIn a selected group of MS patients in relapsing phase no statistically significant difference in PON1 and ARE activities was detected but the mean values for the serum enzyme activities were lower in MS patients.     

Comparative performance of two methods that assess the quality of international normalized ratio measures

ObjectivesTwo methods, Petersen's error grid analysis and Shermock's method to detect clinically important differences, were recently developed to advance the assessment of analytic performance of point-of-care INR devices. Both methods predict when alternate INR measures lead to different clinical decisions. Our goal was to compare their performance characteristics.Design and methodsPerformance characteristics were assessed by comparing the models’ predictions to clinical decisions that were directly measured in a previous experiment.ResultsShermock's method (82% of predictions correct) demonstrated superior predictive performance compared with the error grid analysis (75% of predictions correct, p = 0.008). Shermock's method was particularly superior at identifying the clinical decisions that actually disagreed (79% for Shermock's method vs. 47% for error grid). Consequently, Shermock's method was superior at identifying a POC device with poor performance (79% accuracy vs. 70%, p = 0.006).ConclusionShermock's method had superior performance characteristics and should be integrated into analytic strategies to assess POC INR devices.     

Urinary calcium response to high dose vitamin D3 with calcium supplementation in patients with multiple sclerosis

ObjectiveTo characterize the effect of vitamin D₃ intake on urinary calcium:creatinine ratios across predefined ranges of serum 25(OH)D.DesignPatients with multiple sclerosis (n = 25) received escalating doses of vitamin D₃ (4000–40,000 IU/d) with calcium (1200 mg/d).ResultsUrinary calcium:creatinine was driven by increased 25(OH)D when concentrations were < 75 nmol/L (r = 0.424, p = 0.009) and > 200 nmol/L (r = 0.281, p = 0.01), but no relationship existed when 25(OH)D concentrations were 76–200 nmol/L.ConclusionsA “safe”, physiological range of 25(OH)D concentrations is 75–200 nmol/L.     

Association between serum cortisol and testosterone levels, opioid therapy, and symptom distress in patients with advanced cancer

ContextPatients with advanced cancer often experience symptoms such as pain, anorexia, and fatigue. Opioid therapy for the management of cancer pain may result in neurohormonal dysfunction that may contribute to a patient’s symptom burden.ObjectivesTo examine the association between serum cortisol and testosterone levels, opioid therapy, and symptom distress in patients with cancer.MethodsA retrospective chart review was performed on 77 consecutive patients with advanced cancer referred for symptoms of fatigue or cachexia. We collected information regarding cortisol levels (am or random), testosterone levels (men only), morphine equivalent daily dose (MEDD), and symptom severity measured by the Edmonton Symptom Assessment Scale. Nonparametric correlation analysis was performed.ResultsThe median age was 63 years (range 24–79), and 62% were men (n = 48). Most patients had gastrointestinal (n = 33, 43%) or thoracic (n = 21, 27%) malignancies and were Caucasian (n = 46, 60%). The median random cortisol level was 19.1 μg/dL (Q1–Q3, 13.4–23.8 [normal, 4.3–22.4]), which correlated with MEDD (Spearman coefficient, 0.25, P = 0.032) and symptoms including pain (0.50, P < 0.001), fatigue (0.29, P = 0.012), nausea (0.34, P = 0.003), depression (0.24, P = 0.032), and anxiety (0.25, P = 0.031). Pain and nausea remained significant after Bonferroni correction. Median morning cortisol level (n = 28) was 20.6 μg/dL (Q1–Q3, 16.6–25.4) and significantly correlated with pain (0.55, P = 0.003) after Bonferroni correction. Patients with a MEDD <30 mg/day had a mean random cortisol level of 16.6 μg/dL, whereas patients with a MEDD ≥30 mg/day had a mean random cortisol level of 20.6 μg/dL (P = 0.01). In 44 male patients with cancer, MEDD was inversely correlated with the total testosterone level (?0.52, P = 0.001).ConclusionIn patients with advanced cancer, elevated random cortisol levels were associated with pain and opioid use, although abnormally low levels of cortisol were found to be infrequent. Patients on higher opioid therapy (MEDD >30) had increased cortisol levels, and male patients had lower testosterone levels. Our study suggests that opioid therapy in patients with advanced cancer may inhibit gonadal function while sparing the adrenal axis. Future studies are needed.     

Palliative sedation in advanced cancer patients followed at home: a retrospective analysis

ContextData regarding palliative sedation at home in dying patients are lacking.ObjectivesTo describe the frequency, indication, and modality of palliative sedation (PS) in patients followed at home.MethodsA retrospective analysis of home care cancer patients was performed. Patients who received PS before dying were selected and information about epidemiologic characteristics, indications, duration, drugs, and outcomes was collected.ResultsOf 370 medical charts of patients who died at home, 49 patients received PS before dying. PS was proposed by the team, relatives, or both in 63.3%, 4.1%, and 32.6% of cases, respectively. Delirium alone or in combination with other symptoms was the most frequent indication to begin PS. Midazolam was the most frequently used drug to initiate PS (98%), at a mean dose of 28.1 mg/day, in combination with parenteral morphine (84.7%) at a mean dose of 25.4 mg/day. At the time of death, midazolam was administered in 98% of patients (mean dose 22.3 mg/day), combined with parenteral morphine in 87.8% of patients (mean dose 28.1 mg/day). Satisfaction for physicians and principal caregivers after PS was good in 46 and 48 cases, respectively.ConclusionPS at home seems to be a feasible treatment option among selected patients and makes a potentially important contribution to improving care for those who choose to die at home.     

A spicamycin derivative (KRN5500) provides neuropathic pain relief in patients with advanced cancer: a placebo-controlled, proof-of-concept trial

ContextNeuropathic pain in patients with cancer can be difficult to treat effectively.ObjectivesThe purpose of the study was to determine safety and efficacy of KRN5500, a novel, spicamycin-derived, nonopioid analgesic agent, in patients with advanced cancer and neuropathic pain of any etiology.MethodsThe study was a Phase 2a, multicenter, double-blind, placebo-controlled, dose escalation clinical trial. Patients with refractory neuropathic pain and advanced cancer were randomly assigned 2:1 to receive a maximum of eight single escalating doses of KRN5500 or placebo, ranging from 0.6 to 2.2 mg/m². The primary objective was safety and tolerability. The secondary objective was efficacy, measured by change in average pain intensity on a 0–10 numeric rating scale administered one week after the patient’s final dose.ResultsNineteen patients received treatment (KRN5500 n = 12; placebo n = 7). The most frequently reported adverse events were gastrointestinal symptoms, which were more frequent and severe with KRN5500 than placebo; two (17%) KRN5500 patients discontinued the study because of nausea and vomiting. At study endpoint, KRN5500 exhibited a significant median decrease in pain intensity from baseline of 24% compared with 0% for placebo (P = 0.03). The median for largest weekly reduction in target pain intensity was 29.5% for KRN5500 and 0% for placebo patients (P = 0.02).ConclusionThis proof-of-concept study for KRN5500 in patients with advanced cancer and any type of neuropathic pain found gastrointestinal adverse events to be the predominant safety concern. The results also provided the first indication of clinical and statistical efficacy in reducing pain intensity.     

Pregnancy-associated plasma protein A values in patients with stable cardiovascular disease: use of a new monoclonal antibody-based assay

BackgroundPAPP-A is promising in improving risk stratification and invasive treatment decisions in stable cardiovascular patients. We evaluated the prognostic value of pregnancy-associated plasma protein A (PAPP-A) measured by a novel assay in stable cardiovascular patientsMethodsWe investigated 228 stable cardiovascular outpatients. Blood was drawn for PAPP-A measurement after echocardiography and ergometry prior to heart catheterization. Angiographically we determined severity as well as qualitative characteristics suspect for vulnerability of coronary lesions. After 1108 ± 297 days, follow-up information was obtained by questionnaire mailings and interviews by phone.Results104 patients had coronary stenosis ≥ 70%, 75 had B-type lesions ≥ 50%, 46 showed complex lesions, and 68 were suspected to have vulnerable lesions. Median PAPP-A was 1.76 (interquartile range 1.21, 2.63) μIU/ml in the entire cohort. PAPP-A concentrations did not differ in dependence on coronary artery findings. A cutpoint of 2.7 μIU/ml was derived from receiver–operator characteristics for outcome measures. For this cutoff, Cox proportional hazard models with 19 further clinical variables showed that PAPP-A was predictive for all-cause death (HR 4.73, 95% CI 1.46–15.31, p = 0.01), all-cause death or nonfatal infarction (HR 4.01, 95% CI 1.58–10.13, p = 0.003) and all-cause death, nonfatal myocardial infarction or hospitalization (HR 1.96, 95% CI 1.03–3.70, p = 0.04). The predictive value of PAPP-A did not change substantially after correction for values of cardiac troponin, using a highly sensitive cardiac troponin I research assay.ConclusionsPAPP-A, measured by a new, monoclonal antibody-based assay is a promising prognostic marker in patients with stable cardiovascular disease and an indication for heart catheterization.     

Serum tartrate-resistant acid phosphatase 5b (TRACP5b) activity as a biomarker for bone metastasis in non-small cell lung cancer patients

BackgroundDiagnosis and follow-up of bone metastasis (BMet) in non-small cell lung cancer (NSCLC) patients usually rely on symptoms and image studies. A serum marker of bone resorption may improve the quality of treatment in such patients. Tartrate-resistant acid phosphatase 5b (TRACP5b) is a specific marker for osteoclasts and we proposed it can be used as a marker of BMet in NSCLC patients.MethodsIn November 2002 till August 2008 serum samples were obtained from 141 newly diagnosed stage IIIA, IIIB or IV NSCLC patients and 41 normal subjects. All patients received baseline bone scintinography examination and evaluation of clinical symptoms as a standard of BMet diagnosis. Patients were divided into 2 groups by having BMet (Group I, n = 72) or not (Group II, n = 69). An in-house immunoassay using a TRACP-specific monoclonal antibody, 14G6, was used to measure the serum TRACP5b activity at pH 6.1.ResultsThe mean serum TRACP5b activities of Group I, Group II and normal subjects were 3.50 ± 2.23 U/l, 2.09 ± 0.72 U/l and 2.33 ± 0.52 U/l, respectively. After adjusting for age, stage, gender, and histology in a generalized linear model, Group I has significantly higher TRACP5b activity than Group II (p < 0.001). The receiver operating characteristic analysis established a cutoff value of 2.551 U/l to identify BMet in NSCLC patients with a sensitivity of 63.9% and a specificity of 76.8%. TRACP5b activity declined in patients who responded to treatment (p = 0.047), and elevated in patients who developed new BMet (p = 0.05).ConclusionsSerum TRACP5b activity test is a potentially useful adjunct in diagnosing and monitoring BMet in NSCLC. Further study is warranted to establish its real value in diagnosis and monitoring of BMet in NSCLC patients.     

Characterization of chemosensory alterations in advanced cancer reveals specific chemosensory phenotypes impacting dietary intake and quality of life

ContextTaste and smell (chemosensory) alterations are common and distressing among advanced cancer patients, but their specific nature is poorly described and seldom linked to dietary intake. Details of altered chemosensory perception may help to explain food intake behaviors.ObjectivesOur goal was to characterize chemosensory alterations and their relationship with dietary intake and quality of life (QOL).MethodsAdult advanced cancer patients (n = 192) completed a chemosensory self-assessment questionnaire to characterize changes in their sense of smell and four basic tastes (sweet, sour, salty, and bitter) since the onset of cancer, three-day food record, and QOL questionnaire.ResultsPatients experienced either no alteration in any basic tastes and sense of smell sensations (26% of patients) or one of three altered chemosensory phenotypes: 1) stronger sensations overall (42%), 2) weaker sensations overall (18%), or 3) mixed (some sensations stronger and others weaker, 14%). For individual sensations (sweet, sour, salty, bitter, and smell), stronger sensation was twice more prevalent than weaker sensation (P = 0.035). Patients reporting chemosensory alteration consumed 20%–25% fewer calories per day (P = 0.0018), experienced greater weight loss (P = 0.0036), and had poorer QOL scores (P = 0.0176) compared with patients with no alterations, but results did not vary by chemosensory phenotype. Chemosensory alterations were not related to tumor type (P = 0.884), gender (P = 0.286), or nausea (P = 0.278).ConclusionChemosensory alterations predict dietary intake and QOL; the identification of chemosensory phenotypes provides a rationale to adjust the properties of foods and dietary recommendations in function of the specific nature of these changes.     

Relationship of age-related concentrations of serum FSH and LH with bone mineral density, prevalence of osteoporosis in native Chinese women

BackgroundFollicle-stimulating hormone (FSH) and luteinizing hormone (LH) may play an important role in bone mass regulation in postmenopausal women.MethodsA cross-sectional study of 699 healthy Chinese women, aged 20 to 82 y, was conducted. Serum FSH and LH and BMD were measured at the posteroanterior (PA) spine, lateral spine, total hip, and distal forearm.ResultsThe geometric mean values (± SD) of serum FSH and LH in premenopausal women were 3.94 ± 2.08 and 7.51 ± 2.58 IU/l, respectively, and in postmenopausal women were 28.8 ± 1.88 and 25.6 ± 1.95 IU/l, respectively. The correlation of FSH to BMD at different skeletal regions (r = ? 0.597 – ? 0.492, P = 0.000) was higher than that of LH to BMD (r = ? 0.452 – ? 0.332, P = 0.000). The prevalences of osteoporosis for the quartiles of FSH at various skeletal sites were 0.57%, 0.43%, 27.1%, and 30.9%, respectively; and of LH were 2.14%, 4.43%, 19.5%, and 26.0%, respectively. The prevalence of osteoporosis in 3rd and 4th quartile was more significantly increased than the 1st and 2nd quartile.ConclusionsThese data suggest that FSH and LH levels in circulation are associated with BMD changes and osteoporosis occurrence in Chinese women.     

Effect of somatostatin analogue octreotide on pain relief after major abdominal surgery

BackgroundOctreotide acetate is an 8-amino-acids synthetic octapeptide analogue of somatostatin with much-enhanced duration of action and lower incidence of side effects. We assessed the utility of using intravenous octreotide as an adjuvant to opioid analgesia that might exert a post-operative opioid-sparing effect.MethodsForty-four patients were randomly allocated, to receive either a placebo or intraoperative octreotide 0.33 μg kg^?1 h^?1 intravenous infusion that was maintained in the post-operative period. Patients received for post-operative analgesia an intravenous piritramide patient controlled analgesia (PCA), set to deliver a piritramide 0.02 mg kg^?1 dose.ResultsTwo-way ANOVA revealed significantly fewer (P = 0.0003) mean ± SD weighted piritramide dose requirements in the octreotide group (19.5 ± 6.3 μg kg^?1 h^?1) than in the control group (35.7 ± 8.2 μg kg^?1 h^?1). Dunnett’s two-sided multiple-comparison post hoc test revealed a significant difference between the two groups during the first 22 post-operative hours, following which there were no differences between the two groups. There were no significant differences over time in the mean arterial pressure (P = 0.722), heart rate (P = 0.579) and respiratory rate (P = 0.823) between the octreotide group (80 ± 10 mm Hg, 74 ± 12, 14 ± 2) and the control group (82 ± 9 mm Hg, 76 ± 11, 15 ± 3), respectively.ConclusionWe demonstrated that perioperative octreotide intravenous infusion could be an adjuvant to opioid analgesia as it exerted a piritramide opioid-sparing effect. We encountered more systemic side effects such as nausea, abdominal discomfort, and diarrhea in the octreotide group than in the control group. Our findings could be beneficial to patients who cannot tolerate the adverse effects of opioids.     

Vital and functional outcomes of the first-ever hemispheric stroke, epidemiological comparative study between Kunming (China) and Limoges (France)

BackgroundClinical outcomes and socioeconomic consequences after a stroke may differ between regions.MethodsOne cohort was established prospectively in Kunming (China) to compare with a cohort of 156 stroke patients included in Limoges (France). During 1 year, patients hospitalized within 48 hours for a first-ever hemispheric stroke were included. Demographic data and neurocardiovascular risk factors were registered. Hemiplegia was evaluated. Functional outcome was assessed using the Barthel Index (BI) after 3 months.ResultsOne hundred and eighteen patients were included in Kunming. Patients of Kunming were younger (61.4 ± 13.4 vs 72.3 ± 14.6 years in Limoges, P < 0.0001), more involved in professional activity (36.4% vs 12.8%, P < 0.0001). Survival analysis indicated that mortality did not differ between cohorts, but independently predicted by coma at the 2nd day (HR = 9.33, 95% CI [4.39, 19.78]) and age > 70 years (HR = 6.29, 95% CI [2.36, 16.59]). Despite a better baseline BI for patients of Kunming (50.0 ± 34.9 vs 37.4 ± 34.2, P = 0.0031), after adjustment for confusing, patients in Limoges had a 2.11 OR 95% CI [1.03, 4.31]) to reach a BI > 80 at 3 months.ConclusionsFunctional recovery for patients of Kunming was not as good as expected. The socioeconomic consequences of stroke in Kunming are significant as they involved younger subjects who were still in work.     

A strategy for conversion from subcutaneous to oral ketamine in cancer pain patients: effect of a 1:1 ratio

ContextNo consensus exists about the most appropriate dose ratio for conversion from parenteral to oral ketamine.ObjectivesTo confirm that a 1:1 dose ratio is suitable for converting subcutaneous (s.c.) to oral ketamine in cancer patients.MethodsPatients with opioid poorly responsive cancer pain, who responded to 0.4, 0.6, or 0.8 mg s.c. ketamine bolus, were treated with 0.1, 0.15, or 0.2 mg/kg/h ketamine infusion, respectively. Switching to the oral route, by applying a 1:1 dose ratio, was carried out in patients who experienced adequate pain relief and continued to need ketamine as a coanalgesic. Pain, somnolence, feelings of insobriety, confusion, and cardiovascular parameters were assessed throughout the process.ResultsTwenty-nine patients were enrolled in the study. Ketamine infusion decreased pain intensity from severe to no pain or slight pain in 23 of 29 and six of 29 patients, respectively. The median of s.c. ketamine doses was 0.2 mg/kg/h (range 0.1–0.5). After oral switching, 27 of 29 patients remained as successfully controlled as when receiving s.c. ketamine. The other two patients needed a slight dose ratio readjustment, to 1:1.3 and 1:1.5, to maintain pain control. The median of oral ketamine doses was 300 mg/day (interquartile range 240–382.5). Seven of 29 patients receiving s.c. ketamine developed moderate and transitory side effects, such as feelings of insobriety and somnolence. No side effects were present while receiving oral ketamine. No significant changes were observed in cardiovascular parameters.ConclusionA 1:1 dose ratio for conversion from s.c. to oral ketamine is safe and effective in cancer pain patients.     

Fear of falling as seen in the Multidisciplinary falls consultation

Fear of falling may be as debilitating as the fall itself, leading to a restriction in activities and even a loss of autonomy.ObjectivesThe main objective was to evaluate the prevalence of the fear of falling among elderly fallers. The secondary objectives were to determine the factors associated with the fear of falling and evaluate the impact of this fear on the activity “getting out of the house”.Patients and methodProspective study conducted between 1995 and 2006 in which fallers and patients at high risk for falling were seen at baseline by the multidisciplinary falls consultation team (including a geriatrician, a neurologist and a physical medicine and rehabilitation physician) and then, again 6 month later, by the same geriatrician. The fear of falling was evaluated with a yes/no question: “are you afraid of falling?”.ResultsOut of 635 patients with a mean age of 80.6 years, 502 patients (78%) expressed a fear of falling. Patients with fear of falling were not older than those who did not report this fear, but the former were mostly women (P < 0,001), who experienced more falls in the 6 months preceding the consultation (P = 0.01), reported more frequently a long period of time spent on the floor after a fall (P < 0.001), had more balance disorders (P = 0.002) and finally, were using more frequently a walking technical aid (P = 0.02). Patients with fear of falling were not going out alone as much as the fearless group (31% vs 53%, P < 0.0001). Eighty-two percent of patients in the fearful group admitted to avoiding going out because they were afraid of falling.ConclusionThe strong prevalence of the fear of falling observed in this population and its consequences in terms of restricted activities justifies systematically screening for it in fallers or patients at risk for falling.