Mean Initial Dose Research Articles

Randomized Clinical Trial of an Intravenous Hydromorphone Titration Protocol versus Usual Care for Management of Acute Pain in Older Emergency Department Patients

Opioid titration is an effective strategy for treating pain; however, titration is generally impractical in the busy emergency department (ED) setting. Our objective was to test a rapid, two-step, hydromorphone titration protocol against usual care in older patients presenting to the ED with acute severe pain. This was a prospective, randomized clinical trial of patients 65 years of age and older presenting to an adult, urban, academic ED with acute severe pain. The study was registered at http://www.clinicaltrials.gov (NCT01429285). Patients randomized to the hydromorphone titration protocol initially received 0.5 mg intravenous hydromorphone. Patients randomized to usual care received any dose of any intravenous opioid. At 15 min, patients in both groups were asked, 'Do you want more pain medication?' Patients in the hydromorphone titration group who answered 'yes' received a second dose of 0.5 mg intravenous hydromorphone. Patients in the usual care group who answered 'yes' had their ED attending physician notified, who then could administer any (or no) additional medication. The primary efficacy outcome was satisfactory analgesia defined a priori as the patient declining additional analgesia at least once when asked at 15 or 60 min after administration of the initial opioid. Dose was calculated in morphine equivalent units (MEU: 1 mg hydromorphone = 7 mg morphine). The need for naloxone to reverse adverse opioid effects was the primary safety outcome. 83.0 % of 153 patients in the hydromorphone titration group achieved satisfactory analgesia compared with 82.5 % of 166 patients in the usual care group (p = 0.91). Patients in the hydromorphone titration group received lower mean initial doses of opioids at baseline than patients in the usual care group (3.5 MEU vs. 4.7 MEU, respectively; p ≤ 0.001) and lower total opioids through 60 min (5.3 MEU vs. 6.0 MEU; p = 0.03). No patient needed naloxone. Low-dose titration of intravenous hydromorphone in increments of 0.5 mg provides comparable analgesia to usual care with less opioid over 60 min.

THU0224 Randomized Double-Blind Comparative Effectiveness in RA Patients with Active Disease Despite Methotrexate (MTX): A Comparison of Conventional Disease-Modifying Anti-Rheumatic Drugs with a Biological

BackgroundDouble-blind placebo controlled trials have demonstrated the efficacy of 16 different therapies in RA patients with active disease despite MTX. However, there have been no blinded trials comparing conventional combination...

Polymyalgia rheumatica: diagnosis, prescribing, and monitoring in general practice

BackgroundPolymyalgia rheumatica (PMR) is a common rheumatological disorder of older patients. The majority of UK patients are diagnosed and managed exclusively in general practice. In primary care, it has been shown that there is wide variation in practice, and established diagnostic criteria are infrequently used.AimThis study aims to investigate the diagnostic processes, management, and monitoring of patients with PMR in UK primary care.Design and settingThis is a retrospective cohort study set in primary care.MethodData were extracted from two interlinked primary care databases from north Staffordshire. Patients with PMR were identified using Read Codes and the relevant investigation, prescription, and consultation data were extracted and reviewed.ResultsThree hundred and four patients’ records were analysed. Documentation of symptoms leading to a diagnosis of PMR was found in 248 records (81.6%). A documented process of exclusion of relevant differential diagnoses was demonstrated in 68 (22.4%) patients. The mean initial dose of prednisolone was 21.5 mg. Referral to specialist care was made for 135 (44.4%) patients. Gastric prophylaxis was prescribed in 85 (28.0%) cases. Osteoporosis prophylaxis was prescribed to 183 patients (60.2%); 12 patients (3.9%) developed osteoporosis and 56 (18.4%) developed gastric symptoms that led to GP consultation.ConclusionThe management of PMR in general practice could be optimised. Identified areas for improvement include clear documentation of a process of exclusion of other diagnoses, and prophylaxis for potential treatment complications, including osteoporosis and gastric symptoms.

PIN103 - Treatment Burden Associated With Peginterferon-Based Antiviral Therapy For Patients With Chronic Hepatitis C (Chc) In Japan

Several randomized studies confirmed the efficacy and safety of peginterferon-based antiviral therapy for patients with hepatitis C virus infection. However, various types of patients who were not included in those studies are possibly seeking antiviral therapy in daily practice. The study aim was to analyze those patients and their treatment situation in a real-world setting. A large claims database (Medical Data Vision, Japan; 4/2010 - 6/2012) was retrospectively analyzed. The study patients were those who had evidence of CHC (ICD10: B182) and initiated either the combination therapy with peginterferon + ribavirin (PR) or the triple therapy with peginterferon + ribavirin + telaprevir (PR+T) from November, 2011. A total of 207 patients were identified, with 136 patients initiating PR (median age 56 years) and 71 patients initiating PR+T (median age 60 years). A quarter of patients were aged ≥65 in both therapy groups. 6% of patients given PR and 13% of patients given PR+T were previously diagnosed with hepatocellular carcinoma (HCC). Mean initial doses of peginterferon and ribavirin were similar between PR and PR+T however, mean adherence to the ribavirin dose in PR+T was 78% and lower than PR (95%). Patients requiring hospitalizations for treatment initiation were significantly different between PR and PR+T (71% vs. 93%, P<0.01); lengths of stay were 11.8 and 18.5 days in PR and PR+T, respectively (P<0.01), P-values were not changed after adjusting for patient age, gender, and previous diagnosis of HCC and cirrhosis. The study found that a quarter of patients were elderly and the majority of patients required hospitalization to start treatment with either PR or PR+T. More effective and safer treatment is desirable. Further research is needed to understand how differences in the characteristics of the patients treated with PR+T versus PR impact on treatment adherence and hospitalization patterns observed.

A descriptive study of myoclonus associated with etomidate procedural sedation in the ED

BackgroundMyoclonus is a well-recognized side effect of etomidate when given in induction doses for rapid sequence intubation. Most of the data reported on myoclonus with emergency department (ED) sedation doses are reported as a secondary finding. Study objectivesOur objective was to prospectively quantify the incidence and duration of myoclonus associated with the administration of etomidate in the lower doses given for procedural sedation in the ED. MethodsThis was a prospective descriptive study performed between September 2008 and September 2010 at an urban teaching hospital ED with approximately 50000 patient visits per year. Procedural sedation was performed at the discretion of the treating emergency physician, and adult patients receiving etomidate were eligible for enrollment. The occurrence and duration of myoclonus were observed and recorded. Any interference of myoclonus with the ability to complete the procedure was recorded, and adverse effects were identified. ResultsThirty-four eligible subjects were enrolled, and 36 separate sedation procedures were performed. The mean initial etomidate dose was 0.13 mg/kg (range, 0.077-0.20), and the mean total etomidate dose was 0.15 mg/kg (range, 0.077-0.29). Myoclonus was noted in 26 (72%) of 36 sedations. Mean time to onset of myoclonus was 50 seconds (range, 15-146), and the mean duration was 93 seconds (range, 03-557). Myoclonus interfered with the procedure in only 1 (3%) of 36 attempted procedures, and no procedure was unsuccessful because of myoclonus. ConclusionMyoclonus associated with sedation doses of etomidate was common but rarely interfered with the completion of a procedure.

Fifteen years of GH replacement improves body composition and cardiovascular risk factors

ObjectiveFew studies have determined the effects of more than 5–10 years of GH replacement in adults on body composition and cardiovascular risk factors.Design/patientsIn this prospective, single-center, open-label study, the effects of 15 years of GH replacement on body composition and cardiovascular risk factors were determined in 156 hypopituitary adults (93 men) with adult-onset GH deficiency (GHD). Mean age was 50.5 (range 22–74) years at study start. Body composition was measured using dual-energy X-ray absorptiometry.ResultsThe mean initial GH dose of 0.55 (s.e.m. 0.03) mg/day was gradually lowered to 0.40 (0.01) mg/day after 15 years. The mean serum IGF1 SDS increased from −1.53 (0.10) at baseline to 0.74 (0.13) at study end (P<0.001 vs baseline). Lean soft tissue (LST) increased to 3% above the baseline level at study end (P<0.001). After a 9% decrease during the first year of treatment (P<0.001 vs baseline), body fat (BF) started to increase and had returned to the baseline level after 15 years. Serum levels of total cholesterol and LDL-cholesterol decreased and serum HDL-cholesterol level increased. Fasting plasma glucose increased from 4.4 (0.1) at baseline to 4.8 (0.1) mmol/l at study end (P<0.001). However, blood HbA1c decreased from 5.0 (0.1) to 4.6 (0.1) % (P<0.001).ConclusionsFifteen-year GH replacement in GHD adults induced a transient decrease in BF and sustained improvements of LST and serum lipid profile. Fasting plasma glucose increased whereas blood HbA1c was reduced.

Clinical, Quality of Life, Patient Adherence, and Safety Outcomes of Short-Course (12 Weeks) Treatment with Cyclosporine in Patients with Severe Psoriasis (the Practice Study)

BackgroundApart from clinical outcomes, the "real-world" outcomes of intermittent short-course cyclosporine treatment remain poorly documented.ObjectiveTo evaluate various outcomes of short-course cyclosporine treatment for severe psoriasis; and to describe dermatologists' use of the Rule of Tens.MethodsA 12-week pharmacoepidemiological study; 112 evaluable patients recruited by 43 dermatologists.ResultsThe mean initial cyclosporine dose was 2.88±0.74 mg/kg/day. At 12 weeks, 64.3% of patients were continued beyond the study period at mean dose of 2.51±0.91 mg/kg/day. Percent body surface affected, Psoriasis Area Severity Index score, and patient and physician rating of psoriasis severity decreased significantly, while quality of life (QoL) improved significantly. Median patient satisfaction at 12 weeks was 85 (0~100 scale). Patient-reported non-adherence was 43.9% and 56.1%, respectively at both the time points (p=0.18). In modeling on logarithmized outcomes variables, living along was consistently the single most important (negative) determinant of therapeutic and patient outcomes. Safety and tolerance parameters were similar to the ones reported in the literature. Only 7.3% of physicians correctly identified the measures included in the Rule of Tens and the Rule's criterion for inferring severe psoriasis.ConclusionWith adequate monitoring and patient adherence, cyclosporine treatment reduces the severity of severe psoriasis, improves QoL, and is appropriately tolerated; leading to high patient satisfaction. Social support is a key determinant of therapeutic and patient outcomes and patients living along may require clinical attention. The relevance of the Rule of Tens was not evident.

Clinical efficacy and safety of arbekacin sulfate in patients with MRSA sepsis or pneumonia: a multi-institutional study

Arbekacin (ABK) is an aminoglycoside and widely used in Japan for treatment of patients infected with methicillin-resistant Staphylococcus aureus (MRSA). Although, ABK has concentration-dependent antibacterial activity, the peak serum concentration (C (peak)) of ABK has not yet been fully investigated as an indicator of the efficacy of ABK. The present study was conducted in patients admitted to hospitals affiliated with the ABK Dose Finding Study Group, between October 2008 and June 2011, who had pneumonia or sepsis, the cause of which was identified or suspected to be MRSA. The initial target C (peak) was set at 15-20 μg/mL and therapeutic drug monitoring was conducted. Then the relationship between serum concentration and efficacy/safety of ABK was prospectively examined to obtain sufficient clinical efficacy. In total, 89 patients from 11 clinical sites in Japan were enrolled and 29 of these patients were subjected to efficacy analysis. The mean initial dose and C (peak) were 306.9 mg/day and 16.2 μg/mL, respectively. The efficacy rate was 95 % (19/20 patients) at 5-6 mg/kg or higher, 87.5 % (7/8) for sepsis and 90.5 % (19/21) for pneumonia, and the overall efficacy rate was 89.7 % (26/29). There was no increase in the incidence of adverse events. In conclusion, we recommend the initial dose of ABK at 5-6 mg/kg or higher and the dosage regimen should be adjusted to achieve C (peak) at 10-15 μg/mL or higher in the treatment of patients with pneumonia or sepsis caused by MRSA. This strategy would surely achieve low incidence of adverse events while obtaining high clinical efficacy.

Personalized Treatment with low doses of Lenalidomide and Dexamethasone for Relapsed Multiple Myeloma in frail or Elderly Patients

AbstractAbstract 5049 Background.Treatment of frail or elderly patients with relapsing symptomatic/active Multiple Myeloma (MM) is very difficult due to concomitant diseases, impaired bone marrow reserve, systemic toxicity, relatively decreased renal function and general problems of old age. Dexamethasone and new agents (thalidomide, lenalidomide, bortezomib and bendamustine) have been used in this setting, in most cases with doses adapted to the clinical situation. Aims.To retrospectively analyze the management of frail and/or very elderly MM patients with relapsed and active disease treated with reduced doses of the aforementioned agents in five hospitals in Madrid, Spain. Methods.The files of this group of MM patients were studied. The most common treatment has been the combination of low doses of lenalidomide (len) and of dexamethasone (dex), whereas treatment with reduced doses of other agents has been anecdotal; therefore we analyzed the results of len/dex combinations. Len and dex have been used in lower than standard doses, adapted to the individual initial situation of the patients and tailored according to effect and toxicity throughout treatment. There was no specific protocol and the management of the patients has depended exclusively on the practice and criteria of the treating physicians. Patient risk was stratified following the Salmon and Durie (S&D) score and the International Staging System (ISS). Response was assessed with the IMWG criteria. The study has been approved by the Ethics Committee of Hospital Ramon y Cajal, as coordinating center. Results.38 patients were included in the study. Mean age was 79 years (range 68–90). 30 pts (79%) were older than 75 years and 10 pts had over 85 years. More than half of the patients (21) had two or more comorbidities. Patients had previously received 1 to 5 (m=1. 8) different treatment modalities, including steroids, melphalan (25), bortezomib (20), thalidomide (6) (or their combinations), and others or even APBSCT (3). 23 pts (60%) had IgG (m=4087 mg/dl, range 868–13000); 13 (34%) IgA (m=2115, range 355–4930) and 2 (5%) only light chains. 22 had κ and 15 λ light chains. 19 (50%) had BJ proteinuria. Mean Hemoglobin level was 10. 7 gr/dl (7. 5–14. 1) and mean creatinine level 1. 3 mg/dl (0. 4–12. 9); 28 (74%) had bone disease. 3 pts had S&D stage I, 22 stage II, and another 13 stage III. 13 pts had ISS stage I, 17 had stage II and 7 stage III. Patients received between 1 and 30 cycles of len/dex (m= 8). Median initial Len dose was 10 mg, the majority between 5 and 15mg, although 4 received 25 mg that were rapidly reduced. Mean initial dex dose was 20mg/day for 4 days. 4 pts (10. 5%) achieved Complete Remission (CR) (3 with negative IF), 27 (71%) Partial Remission (PR) (5 with VGPR) and 2 (5%) a significant, but lesser than 50%, reduction of the M-component (Stable Disease, Std). Altogether, overall response (CR+PR+Std) occurred in 33 pts (86%). The best response occurred after 2 to 9 cycles (m=4) of len/dex. Treatment was stopped in 15 patients due to neurological (4) or hematological (1) toxicity, pulmonary embolism (1), unrelated causes (4) and after achieving a plateau response (5). Time to next treatment was 1–30 months, (m=8 mo). 7 pts relapsed after 3–21 months (m=7). 10 patients died, 5 of related (disease progression, cardiac amyloidosis, renal progression to ESRF) and 5 of unrelated (cancer, sepsis, myocardial infarction, congestive heart failure) causes. Grade III-IV bone marrow toxicity occurred in 9 pts and neurological toxicity (PNP) in 5 (all of them had previously been treated with bortezomib or thalidomide). Conclusions.Personalized low doses of len/dex have been the most common treatment for frail/very elderly patients with relapsed MM in our centers and it is an active and tolerable option in this setting. The haematological toxicity was expectable and manageable, but prior treatments with bortezomib or thalidomide were associated with limiting neurotoxicity. Disclosures:No relevant conflicts of interest to declare.

Efficacy of intravenous lacosamide as an add-on treatment in refractory status epilepticus: A multicentric prospective study

ObjectiveTreatment of status epilepticus (SE) has not changed in the last few decades, benzodiazepines plus phenytoin or valproate being the most common treatment. Once this first and second line treatment has failed SE is considered refractory (RSE). This study aimed to assess the efficacy and tolerability of intravenous (iv) lacosamide (LCM) in RSE. MethodPatients with RSE who were treated with ivLCM in six Spanish centers were prospectively included. Efficacy was defined as cessation of seizures after starting ivLCM, with no need for any further antiepileptic drug. All patients had been unsuccessfully treated following the standard protocol (benzodiazepines plus phenytoin or valproate) before ivLCM was added. ResultsThirty-four patients were included, 52.9% men, with mean age of 60.15 years. In 58.9% of patients the etiology was symptomatic, and the most common type of SE was focal convulsive (82.4%). Mean initial bolus dose of LCM was 323.53mg. ivLCM was effective in more than half of patients (64.7%), with termination of SE before 12h in 50% of them. ivLCM was used as a fourth or later option in 76.5% of patients. No serious adverse events attributable to LCM were reported. ConclusionsLCM might be a fast, effective and safe add-on treatment in RSE.

High dose of human plasma‐derived FVIII‐VWF as first‐line therapy in patients affected by acquired haemophilia A and concomitant cardiovascular disease: four case reports and a literature review

Haemostatic control is the first priority in acquired haemophilia A (AHA) and recent consensus recommendations suggest using bypassing agents (BAs) (recombinant activated FVII (rFVIIa) and activated prothrombin complex concentrate) as first-line treatment of bleeds. FVIII concentrates, both plasma-derived and recombinant, may be used with low inhibitor titre, minor haemorrhagic episodes and when bypassing drugs are not available [1]. The use of BAs may be associated with thrombotic complications, especially in the elderly with cardiovascular comorbidity, and should be carried out cautiously, as a literature review reported that 7% of patients treated with rFVIIa experienced thrombotic events [2]. Efficacy of FVIII concentrates in AHA has been reported since the early 1990s. Yet the published reports are retrospective, include few patients and deal with heterogeneous populations (see Table 1). Two main protocols have been recorded in the literature [3,4], but FVIII is often used at a much lower dosage. For instance, the data provided by the EACH2 Registry [5] reporting that the efficacy of FVIII treatment is lower than using BAs would show median doses inferior to those recommended in the literature (initial mean dose 50 U kg , total mean dose for patient 20 000 U, period-treatment range 4–6 days). This letter reports on the experience of our Centre in the use of high-dose human plasma-derived FVIII-VWF (HP-FVIII-VWF) concentrates in four patients affected by AHA and concomitant cardiovascular disease treated with a standardized protocol and include a review of the literature on the usage of HP-FVIII in the treatment of AHA.

Retrospective Evaluation of Enoxaparin Dosing in Patients 48 Weeks' Postmenstrual Age or Younger in a Neonatal Intensive Care Unit

Enoxaparin is the anticoagulant of choice in neonates because of the ease of administration, predictable pharmacokinetics, and reduced adverse effects when compared to heparin. The Chest guidelines recommend that therapy in patients younger than 2 months should be initiated with enoxaparin 1.5 mg/kg administered subcutaneously twice daily. This starting dosage may be inadequate, leading to a delay in achieving therapeutic anti-factor Xa plasma concentrations. To determine an enoxaparin dose for neonatal patients that achieves a therapeutic anti-factor Xa plasma concentration and compare that dose to the recommended enoxaparin dose per published guidelines for this patient population. The study was designed as a single-center chart review. Eligible patients were identified by pharmacy anticoagulation records or a search of the electronic medical record for enoxaparin orders. Patients must have received enoxaparin subcutaneously twice daily and have had a postmenstrual age of 48 weeks or younger. Patients diagnosed with renal failure and those receiving prophylactic doses of enoxaparin were excluded. The mean (SD) initial dose of enoxaparin was 1.4 (0.3) mg/kg subcutaneously twice daily, resulting in 27 of 33 patients (81.8%) having a subtherapeutic anti-factor Xa concentration. A mean enoxaparin dose of 2.0 (0.5) mg/kg was required to achieve a therapeutic anti-factor Xa plasma concentration (p < 0.001). Patients born prematurely required a higher enoxaparin dose (2.2 [0.5] mg/kg) than did those born at full-term gestation (1.8 [0.4] mg/kg; p < 0.05). For patients 48 weeks' postmenstrual age or younger who are treated in a neonatal intensive care unit, a higher initial dose of enoxaparin than that suggested by the Chest guidelines is required to attain a therapeutic antifactor Xa plasma concentration. Premature neonates require a larger starting dose of enoxaparin than do infants born at full-term gestation.

Treatment of methicillin-resistant Staphylococcus aureus ventilator-associated pneumonia with high-dose vancomycin or linezolid

The purpose of this study was to determine the clinical cure rate of high-dose vancomycin for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) ventilator-associated pneumonia (VAP) in critically ill trauma patients. Recent trials suggest that a traditional dose of 1 g q12 hours results in unacceptable cure rates for MRSA VAP. Thus, more aggressive vancomycin dosing has the potential to improve efficacy. Based on pharmacokinetic principles, the goal initial dose at the study center has been 20 mg/kg q12 hours or q8 hours since the 1990s. All patients admitted to the trauma intensive care unit from 1997 to 2008 diagnosed with MRSA VAP were retrospectively reviewed. Diagnosis required bacterial growth ≥ 100,000 colony forming units/mL from a bronchoscopic bronchoalveolar lavage, new or changing infiltrate, plus at least two of the following: fever, leukocytosis or leukopenia, or purulent sputum. Overall, 125 patients with 141 episodes of MRSA VAP were identified. Mean age was 47 years ± 21 years, median Injury Severity Score was 29 (22-43), 70% of patients were male, and the mean length of intensive care unit stay was 38 days ± 35 days. The mean initial vancomycin dose was 18.1 mg/kg/dose with a mean duration of therapy of 11 days. Clinical success was achieved in 88% (125 of 131) of episodes, with microbiological success in 89% (66 of 74) of episodes with a follow-up bronchoscopic bronchoalveolar lavage. Overall mortality was 20% (25 of 125), with death due to VAP in 12 of 25 deaths. Mean initial vancomycin trough concentrations were 10.6 mg/L in the clinical success group and 13.3 mg/L in the clinical failure group (p = not significant). High-dose vancomycin provided an acceptable cure rate for MRSA VAP in critically ill trauma patients. Therapeutic study, level III.

Nonpharmacologic Treatment of Migraine With Low-Dose Propranolol or Amitriptyline

This study evaluated the effectiveness of nonpharmacologic measures combined with low-dose propranolol or amitriptyline for treating severe pediatric migraine. Data were collected from the medical files of 118 patients (mean age, 12.54 ± 3.14 years S.D.). All were treated with nonpharmacologic measures. In addition, 93 children received propranolol (mean initial dose, 0.4 ± 0.17 mg/kg/day S.D.), and 25 received amitriptyline (mean initial dose, 0.26 ± 0.1 mg/kg/day S.D.). Twenty patients were switched from propranolol to amitriptyline during treatment. In both groups, headache frequency was reduced by >50% per month in ~80% of patients. Patients without aura responded significantly better to propranolol than patients with aura (P = 0.02). No significant difference was evident in response to pharmacologic treatment by migraine frequency or type (episodic chronic). No significant difference was evident in response to amitriptyline between patients with or without aura. The response rate was higher than previously reported for placebo. Low-dose propranolol and low-dose amitriptyline, when combined with nonpharmacologic measures, are equally effective in reducing the frequency of migraine in children. Propranolol is preferred because of its lower risk of side effects. An additive effect of nonpharmacologic measures may allow for a reduction in drug dose.

Clinical Experience With Low-Dose Continuous Infusion of Furosemide in Acute Heart Failure

Clinical data are scarce for furosemide administered as a low-dose (<160 mg/24 hours) continuous intravenous infusion in acute heart failure (HF). Our purpose was to evaluate the efficacy and safety of low-dose continuous infusion of furosemide on diuretic response, renal function, and patient outcomes. A retrospective study of patients with acute HF who received furosemide administered as a continuous infusion after initial therapy with intermittent boluses (usually 40-80 mg every 12 hours). End points included mean hourly urine output, incidence of acute renal injury, and outcome disparities of patients who developed acute renal injury. Comparison of patients with preserved and reduced left ventricular ejection fraction (LVEF) was also performed. The study included 150 patients (age 57 ± 13 years, male gender 61%, admission weight 87 ± 32 kg, LVEF 37 ± 15%, 28% preserved LVEF). Mean initial and maximum furosemide doses were 5.1 ± 1.1 mg/h and 6.2 ± 2.2 mg/h, respectively. Mean duration of therapy was 51.4 ± 67.5 hours. Continuous infusion of furosemide was associated with a significant increase in mean hourly urine output compared to baseline (150 ± 77 mL/h vs 116 ± 69 mL/h, P < .001). Acute renal injury developed in 19% of patients, with 70% of those occurring within the first 48 hours of therapy. Mean serum creatinine (baseline 1.55 ± 1.50 mg/dL vs at discharge 1.64 ± 1.61 mg/dL, P = .20) and estimated glomerular filtration rate (baseline 67 ± 39 mL/min vs at discharge 67 ± 43 mL/min, P = .89) did not significantly change over the course of the hospitalization. Development of acute renal injury was associated with poorer outcomes, higher furosemide dose, and longer duration of furosemide therapy. Diuretic response and safety were not different between patients with preserved or reduced LVEF. In patients with acute HF, furosemide administered as a low-dose continuous infusion was effective in achieving diuresis and was not associated with a detectable effect on renal function. This diuretic approach appeared to be similarly effective and safe in patients with preserved LVEF.

Fifteen years of GH replacement increases bone mineral density in hypopituitary patients with adult-onset GH deficiency

ObjectiveFew studies have determined the effects of more than 5–10 years of GH replacement in adults on bone mineral content (BMC) and bone mineral density (BMD).Design/patientsIn this prospective, single-centre, open-label study, the effects of 15 years of GH replacement on BMC and BMD, measured using dual-energy X-ray absorptiometry, were determined in 126 hypopituitary adults (72 men) with adult-onset GH deficiency (GHD). Mean age was 49.4 (range 22–74) years at the initiation of the study.ResultsThe mean initial GH dose of 0.63 (s.e.m. 0.03) mg/day was gradually lowered to 0.41 (0.01) mg/day after 15 years. The mean serum IGF1 SDS increased from −1.69 (0.11) at baseline to 0.63 (0.16) at the study end (P<0.001 vs baseline). The 15 years of GH replacement induced a sustained increase in total body BMC (+5%, P<0.001) and BMD (+2%, P<0.001). Lumbar (L2–L4) spine BMC increased by 9% (P<0.001) and BMD by 5% (P<0.001). In femur neck, a peak increase in BMC and BMD of 7 and 3%, respectively, was observed after 7 years (both P<0.001). After 15 years, femur neck BMC was 5% above the baseline value (P<0.01), whereas femur neck BMD had returned to the baseline level. In most variables, men had a more marked response to GH replacement than women.ConclusionsFifteen-year GH replacement in GHD adults induced a sustained increase in total body and lumbar (L2–L4) spine BMC and BMD. In femur neck, BMC and BMD peaked at 7 years and then decreased towards baseline values.

Epidemiology of pemphigus in the western region of Turkey: retrospective analysis of 87 patients

Background: Pemphigus is a worldwide disease and varies in its clinical profile and epidemiology in different regions of the world. The disease is rare and few epidemiological data are available.Objective: The purpose of this study was to evaluate the epidemiologic, clinical, and therapeutic features of pemphigus in the western region of Turkey.Methods: We retrospectively investigated a total of 87 patients with pemphigus. The parameters including age at diagnosis, sex, diagnostic delay, diagnostic methods, hospitalizations, distribution of skin lesions, duration and dose of therapy, side effects, and duration of follow-up were evaluated.Results: The mean age at the onset was 48 years. The average annual incidence of the disease was seven new patients and estimated annual incidence rate was 0.18 per 100,000 inhabitants. The male-to-female ratio was 1/1.64. All patients were treated with systemic corticosteroids. The mean initial dose was 100 mg prednisolone equivalent. Thirty-three (37.9%) patients received azathioprine as adjuvant therapy. The mean time to control the disease activity was 23 days in our study group. Ten patients (11.5%) were in clinical remission without treatment, 41 patients (47.1%) were on low dose steroid (≤10 mg daily), and 28 (32.2%) were using >10 mg/day corticosteroid at the end of the study period.Conclusion: Pemphigus vulgaris (PV) is the most common clinical subtype in the western part of Turkey. The disease is more frequent in the fifth decade of life and has a female predominance in our region. The patients with both oral mucosa and skin involvement need higher corticosteroid dose, more time to control the disease activity and longer hospitalization time when compared with the patients with oral mucosa involvement alone.

The efficacy and safety of high-dose arbekacin sulfate therapy (once-daily treatment) in patients with MRSA infection

The efficacy and safety of once-daily high-dose arbekacin sulfate therapy for methicillin-resistant Staphylococcus aureus (MRSA) infection were evaluated, with analysis of their relationship to blood drug levels. The study was conducted in patients with pneumonia or sepsis, the cause of which was suspected to be MRSA, who were admitted to the Nagasaki University Hospital or its affiliated hospitals between January 2009 and December 2010. The initial drug dose was set at a level expected to yield the goal peak of 20 μg/ml and a trough level of less than 2 μg/ml, using the Habekacin Therapeutic Drug Monitoring analysis software. Thirteen patients were enrolled: 10 patients had pneumonia and 3 patients had sepsis. Patient mean age was 72.0 years; mean initial drug dose was 269.2 mg. Clinical efficacy at completion of treatment and bacterial eradication-reduction were achieved in 66.7% (6/9) and 62.5% (5/8) of patients, respectively. Incidence of adverse reactions was 38.5% (5/13). In analysis of efficacy in relationship to serum drug levels, the peak drug level was 22.7 ± 5.50 μg/ml, on average, and 15 μg/ml or higher in all 6 responders. Also, in patients with renal dysfunction, it seemed to be essential to ensure a certain peak drug level and to control the trough level appropriately. Although the number of patients was limited, once-daily high-dose arbekacin sulfate therapy may be highly effective, without posing any major safety problems. Further larger-scale studies are needed.

A Combination of Levetiracetam and Tiapride for Outpatient Alcohol Detoxification: A Case Series

Optimal pharmacotherapy of the alcohol withdrawal syndrome (AWS) in outpatient settings is still a matter of discussion. The aim of this evaluation was to examine the efficacy and tolerability of a combination of levetiracetam and tiapride for outpatient alcohol detoxification. This was an open-label evaluation. After screening eligibility for outpatient detoxification, 9 alcohol-dependent patients received levetiracetam and tiapride in a flexible dosage regimen up to 2500 and 300 mg/d, respectively, for a maximum of 7 days. Severity of alcohol withdrawal was assessed daily using the Alcohol Withdrawal Syndrome Scale (AWSS). All patients completed the treatment successfully. The mean initial doses of levetiracetam and tiapride were 2166.7 and 300 mg/d, respectively. AWS as indicated by the AWSS score decreased clearly over 5 days. The combination of levetiracetam and tiapride was well tolerated. Neither treatment discontinuations because of side effects of the medication nor serious medical complications were observed during the detoxification. The results of this evaluation provide first evidence that the combination of levetiracetam and tiapride might be an effective and safe treatment option for mild to moderate AWS in outpatient settings. Further randomized controlled trials are warranted to confirm these preliminary results.

Efficacy and safety of tacrolimus for induction therapy in patients with active lupus nephritis

After the completion of a double-blind placebo-controlled trial, tacrolimus (TAC) was approved for the treatment of lupus nephritis (LN) in Japan. However, the approved maximal dose, 3 mg/day, is almost half the dose used for induction therapy outside Japan. In this study, we retrospectively evaluated the efficacy and safety of low-dose TAC (≤3 mg/day) for induction therapy in 13 adult patients (2 men and 11 women) with active LN. Eight patients were treated for LN flares. Twelve patients underwent renal biopsies: 8 with class IV, 2 with class III + V, 1 with class IV + V, and 1 with class V renal histology, according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification. The mean initial doses of prednisone and TAC were 34.6 ± 14.5 and 2.7 ± 0.6 mg/day, respectively. All the patients achieved a complete remission (CR) at 7.7 ± 6.7 months (mean ± SD) after the last administration of TAC, except for 2 patients who discontinued TAC treatment; 1 because of worsening systemic lupus erythematosus and 1 because of hypertension. Two patients experienced a flare-up after achieving CR. The mean blood TAC concentration 12 h after the last administration (C12) was significantly lower among the patients with flare-ups than among those with a sustained CR (1.5 ± 1.5 vs. 5.1 ± 1.9 ng/mL, P = 0.034). These data showed that low-dose TAC was effective for induction therapy in patients with active LN, although a lower TAC concentration may be associated with a poor outcome.