Cases Of Nausea Research Articles

37 In Search of the Herbert Effect: The Impact of an Emergency Medicine Podcast on the Frequency of Diagnostic and Treatment Patterns in Emergency Departments

Social media is being increasingly utilized by learners in community and academic practice. Among emergency medicine (EM) podcasts, the most highly utilized is EM:Rap. It currently has nearly 20,000 listeners, a significant proportion of the estimated 45,000 practicing emergency physicians in the United States. This study seeks to identify whether there is any association between topic discussion on EM:Rap and the adoption of that topic in clinical practice. For the pilot study, we measured the impact of EM:Rap discussion on the diagnosis of (1) cannabinoid hyperemesis syndrome (CHS), and the performance of emergency department (ED) cardioversion for atrial fibrillation or atrial flutter (EDCAF), as measured on prevalence in the National Emergency Department Sample (NEDS), a nationally representative data set of ED visits. This study was an observational case/control study of ED visits between 2008 and 2013. To analyze CHS, cases were defined as ED visits with nausea or vomiting and a code consistent with cannabis abuse in patients over age 17, based on ICD-9 codes. A time period was defined from 18 months prior to the first report in the medical literature to 18 months after the EM:Rap podcast was released. The primary analytic was the proportion of patients with a diagnosis of nausea or vomiting who also had a diagnosis of cannabis use. We utilized modified sharp regression discontinuity design, accounting for weighting. These data were examined graphically in each time period. Next, a multivariable generalized estimating equations regression model was built using a logit link function and an exchangeable correlation matrix for patient-level data considering only cases of nausea or vomiting from the data set clustered on the treating hospital, including an interaction term between time and time epoch as our primary analytic. To analyze EDCAF, we conducted a similar analysis of adults with a diagnosis of atrial fibrillation, and the dependent variable was a procedure code consistent with cardioversion. We performed an unweighted analysis of 180 million ED visits from the period of February 2008 - January 2013. Over time, there was a linear increase in the rate of CHS diagnosis that did not change significantly in the period after it was discussed on EM:Rap (p=0.2091). Similarly, we found no significant difference in the rate of EDCAF performance in the epoch after it was discussed on EM:Rap (p=0.2900). Despite its significant penetration among ED providers, discussion of a diagnosis (CHS) or a new treatment option (EDCAF) on EM:Rap did not result in any measurable aggregate change in practice, according to a nationally representative sample of claims data. We hypothesize these findings could reflect that topics in social media reflect changes that are already occurring in practice, but that they are not causal in speeding adoption of new diagnostic or treatment alternatives. These topics may be more reflective of current ED practice patterns, rather than being a driver or change in practice.

Effects of human chorionic gonadotropin combined with clomiphene on Serum E2, FSH, LH and PRL levels in patients with polycystic ovarian syndrome.

ObjectiveEffects of human chorionic gonadotropin combined with clomiphene on serum E2, FSH, LH and PRL levels in patients with polycystic ovarian syndrome were analyzed.Methods90 patients with polycystic ovarian syndrome treated from January 2015 to March 2016 were randomly and evenly divided into control group and observation group. Patients in the control group were only treated with clomiphene. On the basis of the treatment in control group, human chorionic gonadotropin was added in the treatment of observation group. The changes of E2, FSH, LH, PRL levels were compared between two groups before and after the treatment. Clinical curative effects of patients in the two groups was evaluated. Adverse reactions during treatment in two groups were observed and recorded. The incidence of adverse reactions was calculated.ResultsSerum E2, FSH, LH and PRL levels in the two groups decreased significantly after treatment compared with that before treatment. The difference is statistical significant (P < 0.05). After the treatment, E2, FSH, LH and PRL levels in the observation group were lower than that in the control group and the difference is statistical significant (P < 0.05). Total effective rate was 64.44% in the control group and 93.33% in the observation group. There were statistically significant difference in clinical curative effects in the two groups (P < 0.05). Different degrees of adverse reactions were found in both groups during treatment, such as nausea, vomiting, anorexia, liver dysfunction. There were 2 cases of nausea, 2 cases of vomiting, 3 cases of anorexia and 1 case of liver dysfunction from the 45 patients in control group. The total incidence of adverse reactions was 17.78% (8/45). There were 1 case of nausea, 1 case of vomiting, 1 case of anorexia and no liver dysfunction from the 45 patients in observation group. The total incidence of adverse reactions was 6.67% (3/45). The total incidence of adverse reactions in the observation group was significantly higher than that in the control group and the difference was not statistically significant (P > 0.05).ConclusionCombined use of human chorionic gonadotropin can significantly reduce serum E2, FSH, LH and PRL levels, improve clinical curative effects and reduce the incidence of adverse reactions. Human chorionic gonadotropin has high application value on the treatment of polycystic ovary syndrome.

Effect of integrated Chinese and western medicine nursing in patients with laparoscopic cholecystectomy

Objective To explore effect of integrated Chinese and western medicine nursing in patient′s wound pain, gastrointestinal dysfunction(first anal exhaust time), postoperative complication rate and total satisfaction after laparoscopic cholecystectomy. Methods A total of 84 patients with gallstone surgery in our hospital admitted between April 2013 to May 2014 were randomly divided into experimental group (42 cases) and control group (42 cases). Control group patients were treated with routine nursing intervention, while experimental group were treated with routine nursing intervention and integrated Chinese and western medicine nursing. The pain which were evaluated using the visual analogue scale (VAS), first anal exhaust time, incidence of complications and patients′ overall satisfaction were compared. Results The VAS score in the control group was (4.6±2.2)and experimental group(2.4±1.2), the difference was statistically significant (P<0.05); postoperative anal exhaust time of the experimental group was(14.3±1.1) h, shorter than the control group′s (7.5±1.2) h(P<0.05). 2 cases of wound infection, 4 cases of nausea and vomiting occurred in the control group, complication incidence rate was 14.3%, in the experimental group, only 1 case showed nausea, vomiting, complication rate was 2.4%, there was a statistically significant difference (P<0.05). The total satisfaction in the experimental group (95.24%) was higher than that of the control group (66.67%), the difference was statistically significant (P<0.05). Conclusions Integrated Chinese and western nursing applied on the patients with laparoscopic cholecystectomy can reduce postoperative pain, shorten the first postoperative anal exhaust time, reduce the postoperative complication rate, and enhance patient′s total satisfaction, which has high clinical application and promotion value. Key words: Integrated Chinese and western medicine nursing; Cholecystectomy; Wound pain; Anal exhaust; Complication

Comparison of Analgesic Effects of Epidural Infusion of Fentanyl and Fentanyl-bupivacaine in Spine Surgery: A Randomized Clinical Trial Study

Background & Aim: Although most patients experience severe pain after major spinal fixation surgery, little attention has been paid to control it with a multi-modal approach. The aim of this study is to select appropriate method of pain management after spinal surgery. Methods & Materials/Patients: This study was a randomized clinically controlled trial in candidates of spondylolisthesis and spinal fixation surgery under general anesthesia. 90 patients were divided into three groups, as follows: 1) Intervention group of epidural fentanyl (F): patient-controlled analgesia (PCA) pump infused 100 µg of fentanyl and 98cc of normal saline at the rate of 3-5 ml/h in the epidural space via an epidural catheter placed by surgeon 2) Intervention group of epidural fentanyl-bupivacaine (FB): PCA pump infused 100 µg of fentanyl and bupivacaine 0.125% at the rate of 3-5 ml/h in the epidural space. 3) IV morphine group (M): No medication was received epidurally. In case of visual analog scale (VAS) score more than four, one mg of IV morphine bolus was administered to patient. The blood pressure, heart rate, respiratory rate and pain severity were recorded at the moment of patient’s transfer from recovery room to the ward and compared in three groups every six hours for 24 hours. The results of this study were analyzed by statistical tests including repeated measures ANOVA, Kruskal-Wallis, Fisher’s exact test and SPSS software 16. P values less than 0.05 were considered statistically significant. Results: The results of the study showed that VAS score in fentanyl-bupivacaine group was significantly lower than that in the two other groups during the first 18 hours. However, VAS score in all groups decreased at 24th hour postoperatively (less than three) suggesting that there was no statistically significant difference between the three groups. In this study, no serious and severe complications were observed except for a few cases of nausea in the control group. Conclusion: Epidural analgesia with fentanyl-bupivacaine is a safe and effective way to postoperative pain management in listhesis and spinal surgeries.

INDUCCION DE LA EVACUACION UTERINA CON PROSTAGLANDINA F2•ALFA INTRAMNIOTICA

En 14 gestantes se realizó la inducción de la evacuación uterina utilizando Prostaglandinas F2-Alfa, administrada por punción trans-abdominal, bajo control ecográfico en cavidad amniótica. 73 casos tenían diagnóstico ecográfico de óbito fetal, 1 paciente tenía múltiples malformaciones fetales (acranea, etc.) y 9 eran enfermedades hipertensivas severas. El 42.1% eran primigestas y el 78.5% nulíparas. Todas tenían el cérvix uterino cerrado. El tiempo de gestación fluctuó entre 20 y 39 semanas y la altura uterina entre 04 y 26 cm. La dosis promedio de PGF-2 Alfa usada fue de 7.5 mg. (5 a 10 mg.); no se extrajo mayor volumen de líquido amniótico. La evacuación uterina sucedió en el 100 % de los casos, entre las 2 a 73 horas posteriores (6.2 horas promedio). En 2 casos se hizo legrado post evacuación. Hubo un caso de náuseas, vómitos e hipotensión. SE CONCLUYE que el uso de PGF2-Alfa intramniótica da excelentes resultados en la evacuación uterina.

Safety and efficacy of intraperitoneal hyperthermic perfusion chemotherapy following laparoscopic palliative resection for gastric cancer patients with peritoneal metastasis

To investigate the safety and efficacy of postoperative intraperitoneal hyperthermic perfusion chemotherapy(IHPEC) following laparoscopic palliative resection for advanced gastric cancer patients with peritoneal metastasis. Between March 2010 and October 2013, 37 patients with advanced gastric cancer were treated by IHPEC(cisplatin 100 mg, 5-fluorouracil 1000 mg and saline 2000 mL) following laparoscopic palliative resection in our department between March 2010 and October 2013 were analyzed retrospectively. Short-term efficacy and adverse reactions were observed. Complete remission (CR), partial remission (PR), stable disease (SD) and progressive disease (PD) were found in 18, 4, 8 and 7 cases respectively, and the total progression-free rate was 59.5%(22/37). The significant improved, improved, stable and progressive cases of Karnofsky performance status were 6, 13, 10 and 8 respectively, and the rate of improved and stable cases was 78.4% (29/37). Serious adverse reactions (class III ( or IIII) were noted in 3 cases (8.1%), including 2 cases of abdominal pain (class III), 1 case of nausea and vomiting. The modality of IHPEC adopting cisplatin plus 5-fluorouracil regimen following laparoscopic palliative resection for advanced gastric cancer patients with peritoneal metastasis is technically feasible and safe, which has certain effect on postponing the progression of gastric cancer.

Application of continuous thoracic paravertebral nerve block guided by nerve stimulator on postoperative pain relief for nephrectomy

To evaluate the effects of continuous paravertebral nerve block after nephrectomy. 60 cases receiving simple nephrectomy,American Society of Anesthesiologists(ASA) grading status I or II, aged from 30 to 65 years, weighing from 45 to 80 kg, male or female, were randomly divided into 2 groups: control group (CEA group ) and continuous paravertebral nerve block group (PVB group ), 30 patients in each one. Both groups were performed with 0.2% ropivacaine 250 ml in continuous infusion, assisted with intravenous morphine patient-controlled analgesia. The blood gas was examined in 6, 12, 24 and 48 h postoperatively, and the VAS scores of quiet state and motion state were assessed.In 48 h postoperation, the total amount of morphine was calculated and the complications cases were recorded. Compared with the CEA group, PaO2 in PVB group increased and PaCO2 declined significantly. There was no difference of VAS score under quiet state, but under the motion state the VAS scores declined significantly, the total amount of morphine reduced[ (5.2 ± 1.2) vs (13.9 ± 1.6) mg) ], the cases of nausea, vomiting, pruritus , orthostatic hypotension decreased and the postoperative first anal exhaust time interval shortened (P < 0.05). Compared with CEA, postoperative administration of PVB for open nephrectomy results in lowering morphine dose as well as side effect related with the use of morphine.

A cocktail of synthetic stimulants found in a dietary supplement associated with serious adverse events.

Food supplements are regularly found to contain pharmacologically active substances. Recently, the food supplement Dexaprine was removed from the Dutch market because it was associated with severe adverse events. Reports to the Dutch Poisons Information Center (DPIC) showed that ingestion of as little as half a tablet caused several cases of nausea, agitation, tachycardia, and palpitations and even one case of cardiac arrest. The remaining tablets of four patients were sent in by different healthcare professionals. Analysis by ultra-performance liquid chromatography quadrupole time of flight mass-spectrometry (UPLC-QTOF-MS) confirmed the presence of synephrine, oxilofrine, deterenol, yohimbine, caffeine, and theophylline. Two more compounds were found which were tentatively identified as β-methyl-β-phenylethylamines. This incident is only the next in a series of similar incidents involving dietary supplements with (undeclared) active substances that are either unsafe or have no known safety profile.

Remifentanil versus placebo for analgesia during external cephalic version: a randomised clinical trial

BackgroundBreech presentation occurs in up to 3% of pregnancies at term and may be an indication for caesarean delivery. External cephalic version can be effective in repositioning the fetus in a cephalic presentation, but may be painful for the mother. Our aim was to assess the efficacy of remifentanil versus placebo for pain relief during external cephalic version. MethodsA randomized, double-blind, controlled trial that included women at 36–41weeks of gestation with non-cephalic presentations was performed. Women were randomized to receive either a remifentanil infusion at 0.1μg/kg/min and demand boluses of 0.1μg/kg, or saline placebo. The primary outcome was the numerical rating pain score (0–10) after external cephalic version. ResultsSixty women were recruited, 29 in the control group and 31 in the remifentanil group. There were significant differences in pain scores at the end of the procedure (control 6.5±2.4 vs. remifentanil 4.7±2.5, P=0.005) but not 10min later (P=0.054). The overall success rate for external cephalic version was 49% with no significant differences between groups (remifentanil group 54.8% vs. control group 41.3%, P=0.358). In the remifentanil group, there was one case of nausea and vomiting, one of drowsiness and three cases of fetal bradycardia. In the control group, there were three cases of nausea and vomiting, one of dizziness and nine cases of fetal bradycardia. ConclusionIntravenous remifentanil with bolus doses on demand during external cephalic version achieved a reduction in pain and increased maternal satisfaction. There were no additional adverse effects, and no difference in the success rate of external cephalic version or the incidence of fetal bradycardia.

Novamin infusion: a new method to cure postoperative shivering with hypothermia

BackgroundPostoperative shivering is a frequent complication of surgery in developing countries and there is no satisfying method to treat it, let alone to cure it. We studied whether intravenous amino acid (AA) infusion can cure postoperative shivering in the postanesthesia care unit. MethodsSixty postanesthesia care unit patients with shivering grade 2 or higher and tympanic temperature <36°C received randomly either infusion of Novamin 18 AAs (2 mL/kg/h), pethidine (0.5 mg/kg), or tramadol (1 mg/kg). Tympanic temperature, shivering grade, and thermal comfort were assessed every 5 min for 60 min. Blood glucose and lactic acid concentrations were measured before and after treatment. Postoperative nausea and vomiting were also recorded. ResultsShivering stopped within 5 min in the pethidine and tramadol groups versus 90% stopped within 15 min in AA group. There were five cases of reshivering in the tramadol group versus none in the AA or pethidine groups. Tympanic temperature increased slowly in all patients but increased significantly faster in the AA group. Thermal comfort improved significantly faster in the AA group versus the other two groups, thermal comfort was significantly higher in the tramadol versus the pethidine group ≥35 min. Blood glucose concentration in AA group increased to 135.18 ± 9.18 mg/dL. There were some cases of nausea and vomiting in pethidine and tramadol groups but none in the AA group. ConclusionNovamin infusion can stop postoperative shivering and alleviates hypothermia and improves thermal comfort more effectively than tramadol and pethidine with less nausea and vomiting and causes a clinically acceptable blood glucose increase with no reshivering episodes.

Local and Systemic Complications after Intravitreal Administration of Anti-Vascular Endothelial Growth Factor Agents in the Treatment of Different Ocular Diseases: A Five-Year Retrospective Study

Purpose: To observe the frequency of complications in patients undergoing intravitreal anti-VEGF injections for different ocular diseases in a five-year period. Materials and Methods: Charts of patients receiving intravitreal anti-VEGF were retrospectively reviewed. Out of 1173 eyes, 762 were treated with bevacizumab, 382 with ranibizumab, and 29 with pegaptanib. Data recorded included demographic information, clinical findings, total injections received, and info about the onset of adverse effects. Results: 12.86% of the eyes treated with bevacizumab presented side-effects, while ratings in the ranibizumab and pegaptanib groups were 15.97% and 20.69%, respectively. Odds ratios calculated comparing incidences after each anti-VEGF are 0.78 (bevacizumab versus ranibizumab, p = 0.152), 0.57 (bevacizumab versus pegaptanib, p = 0.227), and 0.73 (ranibizumab versus pegaptanib, p = 0.508). A total of 185 complications were detected (62.16% after bevacizumab). Ocular side-effects registered were 40 cases of sustained intraocular pression (IOP) elevation, one infectious uveitis, one retinal detachment, and one sub-retinal hemorrhage. Other cases were related to transient IOP elevation immediately after injection. Systemic complications registered were one case of nausea, one episode of chest pain with acute vision loss, and one case of acute blood hypertension. Conclusions: The majority of significant complications occurred in patients receiving multiple bevacizumab administrations. However, results may be affected by the difference in the utilization amount for each drug. AMD patients were the most represented, probably due to greater indication to treatment.

Retrospective analysis of the Gram-positive bacteria-infected cases in the Department of Hematology

This study was purposed to evaluate the efficacy and safety of linezolid, vancomycin and teicoplanin for the treatment of patients infected by Gram-positive bacteria in the Department of Hematology by retrospective analysis. The patients with fever in our department from January to December in 2011 were selected for blood culture with Gram-positive bacteria and treated with linezolid, vancomycin or teicoplanin alone.Various parameters were recorded before and after treatment, such as fever time, respiratory symptoms, physical signs, radiographic changes, blood and biochemical routine, and adverse reactions. The efficacy and safety of linezolid, vancomycin and teicoplanin were compared according to the fever abating time, bacterial clearance rate, clinical efficiencies and adverse events. The patients were divided into linezolid group (15 patients), vancomycin group (17 patients) and teicoplanin group (20 patients). The results showed that the mean time of fever abating in linezolid group was (4.43 ± 3.15)d, bacterial clearance rate and clinical efficiency in linezolid group were 55.56% and 86.67%, respectively. The above three data in vancomycin group were (6.83 ± 4.67)d, 54.54% and 76.47% respectively, and were (5.57 ± 4.16)d, 41.67% and 80.00% in teicoplanin group respectively. There was no statistically significant difference between three groups (P > 0.05). There were one case of diarrhea and two cases of thrombocytopenia in the linezolid group, and one case of nausea and two cases of creatinine increase in the vancomycin group. There were three cases of thrombocytopenia in the teicoplanin group. The thrombocytopenia in five cases and the hemogram drop in patients with leukemia after treatment were overlapped, their drug treatment did not stop, but their thrombocytopoiesis recovered to normal-level, thus the drug treatment were considered as no relation with thrombocytopenia. It is concluded that the treatment efficacy between linezolid, vancomycin and teicoplanin for Gram-positive bacterial infections is not statistically different, but linezolid maybe have advantage over vancomycin and teicoplanin in fever abating time, bacterial clearance rate and clinical efficiency.

Single-Dose, Randomized Crossover Comparisons of Different-Strength Imatinib Mesylate Formulations in Healthy Korean Male Subjects

BackgroundImatinib mesylate is used to treat chronic myeloid leukemia and advanced gastrointestinal stromal tumors. ObjectiveThe purpose of this study was to compare the pharmacokinetics of 2 different strengths of the imatinib formulation containing 100 mg (reference) and 400 mg (test) to satisfy the regulatory requirement for marketing. MethodsA single-center, randomized, single-dose, open-label, 2-period, 2-sequence, comparative crossover study with a 14-day washout period was conducted in 30 healthy male volunteers. Plasma samples for the drug analysis were collected up to 72 hours after drug treatment. Participants received either the reference (4 tablets of 100-mg imatinib) or the test (1 tablet of 400-mg imatinib) formulation during the first period and the alternative formulation during the second period. The safety profiles and tolerability of the 2 formulations were also assessed based on physical examinations, laboratory tests, a 12-lead ECG, and vital signs. ResultsThirty participants were initially enrolled; their mean (SD) age, height, weight, and body mass index were 24.9 (2.0) years (range, 23–30 years), 174 (5) cm (range, 164–185 cm), 69.9 (2.0) kg (range, 54.1–87.4 kg), and 23.0 (2.0) kg/m2 (range, 18.5–26.9 kg/m2); 28 healthy participants completed both treatment periods. Two subjects did not complete the study because they withdrew consent for personal reasons. The observed mean (SD) Cmax, AUC0–last, and AUC0–∞ values for the reference formulation were 1792 (357) ng/mL, 28,485 (6274) ng · h/mL, and 29,079 (6371) ng · h/mL, respectively. Corresponding values for the test formulation were 1710 (312) ng/mL, 27,222 (4624) ng · h/mL , and 27,872 (4751) ng · h/mL. The geometric mean ratios (90% CIs) between the 2 formulations at the 400-mg dose of imatinib were 0.9579 (0.9054–1.0136) for Cmax, 0.9652 (0.9174–1.0155) for AUC0–last, and 0.9679 (0.9203–1.0179) for AUC0–∞, respectively. During the study period, 6 adverse events (3 for the reference and 3 for the test formulation) were reported; all were transient, mild, and resolved completely during the treatment period. There were 4 cases of nausea and 1 case each of dizziness and oropharyngeal pain. Four adverse events were considered related to the study drugs. ConclusionsThe results showed that despite the different strengths of the 2 imatinib formations, the test and reference formulations both met the regulatory criteria for pharmacokinetic equivalence at a dose of imatinib 400 mg in these healthy Korean male subjects. Both imatinib formulations seemed to be generally well tolerated. ClinicalTrials.gov identifier: NCT01270984.

Effect of Oral Clonidine on Hemodynamic Response During Surgery

Clonidine is an alpha 2-adrenoceptor agonist. It has recently, however, found a new and possibly significant role in anaesthesia and the treatment of pain. Diazepam has been used as a drug for premedication for years but oral clonidine has not been used as premedication even though it is cheaper and has longer postoperative analgesic effect. This prospective, double blind randomized study was conducted in department of anaesthesiology, institute of medicine, TUTH. A total 60 consecutive patients scheduled for abdominal gynaecological surgeries were randomized to cloni­dine or diazepam premedication group and received these drug one hour before surgery planned under spinal anaesthesia. Intraoperative haemodynamic changes in terms of blood pressure, heart rate, oxygen saturation, were recorded. Hypotension was occurred in 9(15%) in clonidine group and 10(16.7%) in diazepam group, (p value&gt; 0.05). During surgery, bradycardia was noted in 6(10%) vs. 3(5%) patient in diazepam and clonidine group respectively (p value &gt;0.05). Nausea, shivering, restlessness were other side effects seen during surgery in both clonidine and diazepam group (33.33% vs. 36.66%). Although few more cases of nausea (1 vs. 5) with clonidine and few more cases of restless (3 vs. 7) were noted with diazepam , the overall difference was not statistically significant between two groups (p value &gt;0.05). Oral clonidine premedication had similar hemodynamic response to diazepam. It is cheaper and has longer postoperative analgesic effect as well as similar sedative effect. Nepalese Heart Journal | Volume 7 | No.1 | November 2010 (special issue) | Page 8-14 DOI: http://dx.doi.org/10.3126/njh.v7i1.8495

Comparison of gatifloxacin and fleroxacin on respiractory infections

Objective To compare the clinic effects of gatifloxacin and fleroxacin on respiractory infections.Methods 160 patients of low-moderate respiractory infections were divided into observation group (80 cases) and control group (80 cases).Under common therapy,the observation group accepted gatifloxacin injection while the control group accepted fleroxacin injection.The effective rate,bacterial clearance rate and untoward effect were compared between the two groups.Results The effective rate of observation group was obviously higher than control group (88.8％ vs 72.5％,x2 =3.16,P ＜ 0.05).The bacterial clearance rate of observation group was obviously higher than control group (90.0％ vs 78.8％,x2 =6.28,P ＜ 0.05).There were 5 cases of nausea and vomiting in observation group while 3 cases of nausea and 2 cases of nausea and vomiting in control group.The diverse of untoward effect of two groups had no significance (x2 =0.03,P ＞ 0.05).Conclusion Gatifloxacin has a better clinic effect than fleroxacin.Gatifkoracin doesn't increase the untoward effect on respiractory infections. Key words: Respiractory infections ; Gatifloxacin; Fleroxacin

Amoxicillin for acute lower-respiratory-tract infection in primary care when pneumonia is not suspected: a 12-country, randomised, placebo-controlled trial

Lower-respiratory-tract infection is one of the most common acute illnesses managed in primary care. Few placebo-controlled studies of antibiotics have been done, and overall effectiveness (particularly in subgroups such as older people) is debated. We aimed to compare the benefits and harms of amoxicillin for acute lower-respiratory-tract infection with those of placebo both overall and in patients aged 60 years or older. Patients older than 18 years with acute lower-respiratory-tract infections (cough of ≤28 days' duration) in whom pneumonia was not suspected were randomly assigned (1:1) to either amoxicillin (1 g three times daily for 7 days) or placebo by computer-generated random numbers. Our primary outcome was duration of symptoms rated "moderately bad" or worse. Secondary outcomes were symptom severity in days 2-4 and new or worsening symptoms. Investigators and patients were masked to treatment allocation. This trial is registered with EudraCT (2007-001586-15), UKCRN Portfolio (ID 4175), ISRCTN (52261229), and FWO (G.0274.08N). 1038 patients were assigned to the amoxicillin group and 1023 to the placebo group. Neither duration of symptoms rated "moderately bad" or worse (hazard ratio 1.06, 95% CI 0.96-1.18; p=0.229) nor mean symptom severity (1.69 with placebo vs 1.62 with amoxicillin; difference -0.07 [95% CI -0.15 to 0.007]; p=0.074) differed significantly between groups. New or worsening symptoms were significantly less common in the amoxicillin group than in the placebo group (162 [15.9%] of 1021 patients vs 194 [19.3%] of 1006; p=0.043; number needed to treat 30). Cases of nausea, rash, or diarrhoea were significantly more common in the amoxicillin group than in the placebo group (number needed to harm 21, 95% CI 11-174; p=0.025), and one case of anaphylaxis was noted with amoxicillin. Two patients in the placebo group and one in the amoxicillin group needed to be admitted to hospital; no study-related deaths were noted. We noted no evidence of selective benefit in patients aged 60 years or older (n=595). When pneumonia is not suspected clinically, amoxicillin provides little benefit for acute lower-respiratory-tract infection in primary care both overall and in patients aged 60 years or more, and causes slight harms. European Commission Framework Programme 6, UK National Institute for Health Research, Barcelona Ciberde Enfermedades Respiratorias, and Research Foundation Flanders.

Long-Term Safety and Efficacy of Lubiprostone in Opioid-Induced Bowel Dysfunction in Patients with Chronic, Non-Cancer Pain: Results of a Phase 3, Open-Label Clinical Trial Presidential Poster

Purpose: Chronic use of opioid analgesics for the treatment of non-cancer pain results in opioid-induced bowel dysfunction (OBD) in a significant proportion of patients. Lubiprostone, a locally-acting chloride channel (ClC-2) activator, has been shown to counteract the adverse gastrointestinal effects of opioids via this mechanism in nonclinical studies as well as in two 12-week, placebo-controlled clinical trials. The current study evaluates the safety and efficacy of lubiprostone over 9 months of open-label treatment in an OBD patient population. Methods: 439 adult patients (59.9% female) with baseline-confirmed OBD were enrolled from two 12-week, placebo-controlled, double-blinded studies and received lubiprostone, 24 mcg twice daily (BID), for up to 9 months. Inclusion criteria required consistent treatment with a full opioid agonist for the duration of the study. OBD was defined as having, on average, less than 3 spontaneous bowel movements (SBMs)/week, with 25% or more of the BMs having hard to very hard stool consistency, resulting in a sense of incomplete evacuation, and/or associated with moderate or worse straining during the 2-week baseline period. The primary objective of the study was to evaluate the safety of chronic lubiprostone therapy in patients with OBD. Efficacy outcomes were also assessed. Results: Overall, 24.6% of the patients reported treatment-related adverse events (AEs) during the 9-month study, the most common of which were nausea, diarrhea, and headache (5.0%, 4.6%, and 1.6% of patients, respectively). No treatment-related serious AEs were reported. Nausea and diarrhea were cited as reason for withdrawal in 5 (1.1%) and 5 (1.1%) subjects, respectively, and only 2 cases of nausea and 2 cases of diarrhea were rated as severe. Patient reliance on rescue medication was substantially decreased during the course of the study (33.0% of patients reporting use at Month 1 vs. 18.6% at Month 9). Statistically significant changes from baseline were reported at each month for SBM frequency, with mean weekly SBM frequencies ranging from 4.9 to 5.3 SBMs per week as compared to a pre-treatment SBM frequency of 1.4 SBMs per week (p<0.001 vs baseline at all months). Patient ratings of average degree of straining with SBMs, stool consistency, constipation severity, abdominal bloating, abdominal discomfort, and bowel habit irregularity were also statistically significantly improved from baseline during the entire treatment period (p<0.001 at all treatment months). Conclusion: Lubiprostone treatment was well-tolerated and resulted in overall improvement in symptoms and signs of OBD in this 9-month, open-labeled study. Disclosure: Dr. Spierings - Consultant and Advisory Committee/Board Member: Sucampo. Ms. Lindner - Employee: Sucampo. Dr. Woldegeorgis - Employee: Sucampo. Ms. Joswick - Employee: Sucampo. Dr. Ueno - Employee, Stockholder/Ownership Interest, Patent Holder: Sucampo.

Vorinostat in Combination with Pegylated Liposomal Doxorubicin (PLD) and Bortezomib (B) in Patients with Relapsed/Refractory Multiple Myeloma (R/R MM): Final Results of a Phase I Study,

Abstract 3985 Introduction:Although the combination of PLD and B improved time to progression (TTP) compared with B alone in patients (pts) with R/R MM, the overall response rate (ORR) of the regimen was only 44%, while TTP was 9.3 months. As such, strategies that build upon the efficacy of this regimen are needed. Vorinostat (V) is a histone deacetylase inhibitor that has demonstrated additive to synergistic activity with proteasome inhibitors and anthracyclines in preclinical models of MM. We therefore conducted a phase I study evaluating the safety and preliminary efficacy of V when combined with the PLD/B backbone.Patients and Methods: Pts were treated with standard doses of B and PLD (B 1.3mg/m2 on D1, 4, 8, 11, and PLD 30mg/m2 on D4) and escalating doses of V from either D4-11 or D1-14 of a 3-week cycle. Dose escalation followed a standard 3 + 3 design. Eligibility criteria included a diagnosis of relapsed or relapsed/refractory MM, absolute neutrophil count ≥1.0×109/L, platelets ≥100×109/L, creatinine clearance ≥30mL/min, and adequate hepatic and cardiac function. The primary objective was to determine the dose limiting toxicities (DLTs) and maximum tolerated dose (MTD) of the regimen and the secondary objective was to assess preliminary efficacy. Results:32 pts were enrolled at the following dose levels:Dose LevelVorinostat Dose# of patients# evaluable for toxicity# evaluable for DLT# evaluable for response1200mg D4-1133332300mg D4-1144333400mg D4-1177674300mg D1-146666MTD Expansion300mg D4-1112121212The median age was 61 (39–75) and median β2-microglobulin 3.57 mcg/mL (1.26–10.6). 69% of the pts were male, 31% female. The median time from diagnosis was 46 months (13–155) and median number of prior lines of therapy 2 (1–9). 78% of pts had received prior B, 56% PLD or doxorubicin, 91% thalidomide and/or lenalidomide, and 66% autologous and/or allogeneic stem cell transplantation. 44% (11 of 25 pts) had disease refractory to prior B-based therapy. The median number of complete cycles administered was 6 (0–15). No patients on dose level 1 or 2 suffered DLTs. One of 6 pts on dose level 3 had a DLT consisting of grade 4 systolic dysfunction in the setting of atrial flutter, which subsequently resolved. Two of 6 pts at dose level 4 experienced grade 4 thrombocytopenia in cycle 1, establishing dose level 3 as the MTD. Nine pts experienced serious adverse events at least possibly attributable to protocol therapy, including the 1 case of systolic dysfunction/atrial flutter noted above, 2 cases of nausea and vomiting with dehydration, and diarrhea, diastolic dysfunction, upper respiratory infection, syncopal episode and hypertension in 1 pt each. Grade 3 neutropenia was seen in 34% of pts (3% grade 4). 4 pts had grade 3 infections (1 attributed to protocol therapy), but no grade 4 infections were seen regardless of attribution. Grade 3 and 4 thrombocytopenia was documented in 16% and 34%, but no serious hemorrhagic events were seen. Non-hematologic toxicity at least possibly attributable to therapy included fatigue in 63% (16% grade 3, 0% grade 4). GI toxicity was common with anorexia, constipation, diarrhea, nausea and vomiting occurring in 47% (3% grade 3), 50%, 81% (16% grade 3, 3% grade 4), 78% (9% grade 3) and 50% (9% grade 3) of pts, respectively. Peripheral neuropathy at least possibly attributable to therapy was seen in 38% of pts (6% grade 3), while hand-foot syndrome was seen in 25% (9% grade 3). There were no deaths on study. Among 31 evaluable pts, the ORR using International Uniform criteria was 65% (95% confidence interval (CI): 45–81%), and the ≥very good partial remission (VGPR) rate was 29% (95% CI: 14–48%). The ORR + minimal response (MR) rate was 74% (95% CI: 55–88%). Of 14 pts with B-sensitive disease, there was 1 MR, 5 PRs and 5 VGPRs. Two PRs, 2 VGPRs and 1 complete remission (CR) were documented in 6 pts with B-naïve disease. Notably, there were 2 MRs, 4 PRs and 1 CR out of the 11 pts with B-refractory disease. Conclusions:The MTD of vorinostat when added to the PLD/bortezomib backbone is 400 mg administered daily on days 4–11. The ORR is highly promising, with responses seen in pts with bortezomib-naïve, -sensitive and -refractory disease. Although serious toxicities were infrequent, constitutional and GI side effects were highly prevalent. All together, our data support further development of this combination in pts with MM, with special attention to developing strategies and guidelines to better ameliorate toxicity. Disclosures:Voorhees:Merck: Research Funding; Celgene: Research Funding; Centocor Ortho Biotech: Research Funding; MedImmune: Consultancy; Pfizer: Research Funding. Off Label Use: Vorinostat for the treatment of relapsed and relapsed and refractory multiple myeloma. Gasparetto:Millennium Pharmaceuticals: Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees. Richards:Merck: Consultancy. Garcia:Millennium Pharmaceuticals: Speakers Bureau; Sigma-Tau: Speakers Bureau. MacLean:Novartis: Speakers Bureau. Orlowski:Millennium Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Honoraria; Johnson and Johnson: Research Funding.

Pharmacokinetic Comparison of Orally Disintegrating and Conventional Donepezil Formulations in Healthy Korean Male Subjects: A Single-Dose, Randomized, Open-Label, 2-Sequence, 2-Period Crossover Study

Background Donepezil is a potent inhibitor of acetylcholinesterase, an enzyme that is targeted in the treatment of Alzheimer's disease. Objective The purpose of this study was to compare the pharmacokinetic characteristics of orally disintegrating (test) and conventional (reference) donepezil formulations to satisfy the regulatory requirement for marketing. Methods A single-center randomized, single-dose, open-label, 2-way crossover study with a 21-day washout period was conducted in 22 healthy volunteers. Plasma samples for the analysis of donepezil were collected up to 240 hours after drug administration. Participants received either reference or test drug formulation of 10 mg donepezil in the first period and the alternative formulation in the second period. Plasma concentrations of donepezil were determined by validated high-performance liquid chromatography coupled to tandem mass spectrometry detection. Pharmacokinetic parameters, including C max and AUC, were determined by noncompartmental analysis. ANOVA was carried out using log-transformed C max and AUC, and the mean ratios and their 90% CIs were calculated. The safety profiles and tolerabilities of the 2 formulations were also assessed based on laboratory tests, 12-lead ECGs, vital signs, and physical examinations. Results Of the 22 participants initially enrolled, 18 healthy Korean participants completed both treatment periods. Four subjects did not complete both treatments: 3 subjects withdrew consent for personal reasons, and 1 subject experienced adverse events. No significant differences in pharmacokinetic parameters between the 2 formulations were observed. The mean (SD) age, height, and weight of the participants were 25.8 (4.1) years, 173.6 (5.7) cm, and 68.9 (7.8) kg, respectively. The mean (SD) C max, AUC last, and AUC inf for the reference formulation were 33.26 (6.58) ng/mL, 1521.69 (344.04) ng × h/mL, and 1691.46 (443.05) ng × h/mL, respectively. Corresponding values for the test formulation were 34.23 (6.79) ng/mL, 1554.33 (390.23) ng × h/mL, and 1718.27 (447.03) ng × h/mL, respectively. The median T max was 2 hours (range, 1–3 hours) for the reference and test formulations. The geometric mean ratios (90% CI) between the 2 formulations of donepezil were 102.9 (96.8–109.5) for C max, 102.3 (96.1–108.9) for AUC last, and 101.6 (95.4–108.2) for AUC 0–∞, respectively. During the study, 15 and 14 adverse events were reported for the reference and test formulations, respectively, and all were transient, mild, and resolved during the treatment period. These adverse events included 7 cases of nausea, 3 cases of headache, and 1 case each of dizziness, vomiting, chills, and sweating. All adverse events were considered related to the study drugs. Conclusion This study found that the test and reference formulations met the regulatory criteria for pharmacokinetic equivalence in these fasting healthy Korean male subjects. Both donepezil formulations appeared to be generally well tolerated. ClinicalTrials.gov indentifier: NCT01297036.

The clinical efficacy and safety of the FVIII/VWF concentrate, BIOSTATE®, in children with von Willebrand disorder: a multi-centre retrospective review

Factor replacement with BIOSTATE(®), a factor VIII (FVIII)/von Willebrand factor concentrate, forms the mainstay of treatment for children with von Willebrand disorder (VWD) in Australia and New Zealand. However, published data on the clinical efficacy and safety of BIOSTATE in the VWD paediatric population are limited. We retrospectively assessed the efficacy and safety of BIOSTATE in 43 children with VWD who received treatment for surgery, non-surgical bleeds or continuous prophylaxis at eight paediatric haemophilia centres in Australia and New Zealand. Data were collected on patient demographics, disease history, treatment history, dosage, administration, adverse reactions, concomitant medications and excessive bleeding events. BIOSTATE provided excellent/good haemostatic efficacy in 90% of surgical procedures (n = 42) with a mean daily FVIII dose of 47 IU FVIII:C kg(-1) and a median treatment duration of 3 days. Excellent/good haemostatic efficacy was achieved in 94% of non-surgical bleeding events (n = 72) with a mean FVIII dose of 45 IU FVIII:C kg(-1) day(-1) and a median treatment duration of 1 day. There were no bleeding events attributable to lack of efficacy. One case of nausea, possibly related to BIOSTATE administration, was reported. These results suggest that BIOSTATE is safe and effective for the treatment and prophylaxis of bleeding in children with VWD.