Drug Administration Interval Research Articles

Desensitization for the Prevention of Drug Hypersensitivity

Drug desensitization is a treatment strategy for patients with hypersensitivity to essential drugs without alternatives. The gradual increase in the drug dosage from low doses to therapeutic levels induces a transient immune tolerance to the culprit drug. Although desensitization has traditionally been recommended for IgE-mediated immediate hypersensitivity, this indication has recently been expanded to include non-IgE-mediated immediate responses, nonimmunological responses, and T-cell mediated delayed hypersensitivity reactions. Although the exact mechanism behind desensitization remains unclear, the process is thought to attenuate various intracellular signals in target cells through the high-affinity IgE receptor (FcɛRI) internalization, alteration in signaling pathways in mast cells and basophils, reduction in Ca2+ influx, and production of anti-drug IgG4 blocking antibody. Desensitization can be used for the safe administration of anti-neoplastic agents, antibiotics, aspirin, and nonsteroidal anti-inflammatory drugs. Various desensitization protocols have been proposed for each drug. The optimization of drug concentration, target dosage, administration interval, and route of administration is key to successful desensitization. In addition, the desensitization protocol should be individualized for each patient with consideration of the severity of the initial hypersensitivity response, the characteristics of the culprit drug, and the nature of the breakthrough reactions.

Disease Activity-Guided Stepwise Tapering but Not Discontinuation of Biologics Is a Feasible Therapeutic Strategy for Patients with Ankylosing Spondylitis: Real-World Evidence.

To analyze the history of biologics usage in patients with ankylosing spondylitis (AS) in China and to evaluate the impact of drug reduction and withdrawal on disease activity. Drug administration intervals and disease activity indexes in patients with AS who regularly used etanercept (ETN) biosimilars for more than 1 year and those who withdrew the drugs during the same period in a single center were analyzed retrospectively. A total of 108 patients with AS who used ETN biosimilars for more than a year were recruited in this study for analysis. (1) Overall, 98.1% patients with AS increased the intervals between drug administrations, averaging from 4.57 ± 0.15days during 0-3months to 8.53 ± 0.43days during 3-6months, and to 10.49 ± 0.39days during 6-12months. Compared with the baseline parameters, after 3-month and 12-month treatments disease activities were improved significantly, including Patient Global Assessment (PTGA), overall back pain, nocturnal pain, fatigue, Ankylosing Spondylitis Disease Activity Score-C-Reactive Protein (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Bath Ankylosing Spondylitis Functional Index (BASFI). (2) Only 59.3% used ETN biosimilars with full dose (3.5days' interval) in the first 3months. At baseline, disease activities of these patients were higher than those with reduced dose (5.9days' interval). However, at 12months of drug administration there was no significant difference in the overall length of drug administration intervals and disease activities between the two groups. (3) Twenty patients with low disease activity (LDA) discontinued therapy spontaneously; after 3months, 55% of them experienced disease recurrence (∆ASDAS ≥ 0.9). Spontaneous dose reduction was a common phenomenon among patients with AS in China, which becomes more notable with increasing relief of symptoms. Most patients could maintain an LDA state after dose reduction. Compared with dose reduction, ETN biosimilar withdrawal was more likely to induce disease recurrence. Therefore, disease activity-guided individualized stepwise tapering may become one of the feasible therapeutic strategies for AS in the future.

Abstract 11817: The Effect of Time to Treatment With Antiarrhythmic Drugs on Return of Spontaneous Circulation in Shock Refractory Out-of-Hospital Cardiac Arrest: A Secondary Analysis of the ALPS Randomized Controlled Trial

Purpose: The effects of amiodarone and lidocaine on the return of spontaneous circulation (ROSC), relative to time to treatment in out of hospital cardiac arrest (OHCA) patients is unknown. We conducted a post-hoc analysis of the Resuscitation Outcomes Consortium Amiodarone, Lidocaine, Placebo (ROC ALPS) randomized trial examining the association of time to treatment with ROSC at emergency department (ED) arrival. Method: In the ROC ALPS trial, adults with non-traumatic OHCA with initial VF/pVT after ≥ 1 shock were randomized to receive amiodarone, lidocaine or placebo. We used logistic regression to examine the association of time to treatment (911 call to study drug administration interval) with ROSC at ED arrival. Results: Overall, 1112 (36.7%) patients had ROSC at ED arrival. Time to treatment data were available for 2994 (99%) of the patients. The proportion of patients with ROSC at ED arrival decreased as time to drug administration increased, in amiodarone (OR 0.92, 95% CI 0.90-0.94 per min increase), lidocaine (OR 0.95, 95% CI: 0.93-0.96) and placebo (OR 0.95, 95% CI: 0.93-0.96) arms. The odds of ROSC at ED in the amiodarone group (versus placebo) changed in relation to the time of drug administration (OR 0.96, 95% CI: 0.93-0.99). With short times to drug administration, ROSC was higher in amiodarone versus placebo recipients, whereas ROSC was higher with placebo at later times. Comparing lidocaine to placebo, ROSC rate increased at all times (OR 1.29, 95% CI: 1.07-1.59); there was no time to drug administration effect (OR 1.00, 95% CI: 0.97-1.03). Among all patients, survival at hospital discharge was 21.0%, 24.4%, and 23.7% for placebo, amiodarone and lidocaine respectively. Conclusion: Amiodarone’s efficacy in restoring ROSC declined with longer duration of arrest, potentially due to its adverse hemodynamic effects. Overall, amiodarone and lidocaine had similar effects on mortality; in this study, ROSC at ED arrival trend did not reflect the overall survival rate

THE EFFECT OF TIME TO TREATMENT WITH ANTIARRHYTHMIC DRUGS ON OUTCOMES IN SHOCK REFRACTORY OUT-OF-HOSPITAL CARDIAC ARREST: A SECONDARY ANALYSIS OF THE ALPS RANDOMIZED CONTROLLED TRIAL

<h3>BACKGROUND</h3> The relationship between time to treatment in patients with out-of-hospital cardiac arrest (OHCA) and survival outcomes, and the interaction of time to treatment and antiarrhythmic drug effect, is not precisely known. We conducted a post-hoc analysis of the Resuscitation Outcomes Consortium Amiodarone, Lidocaine, Placebo (ROC ALPS) randomized controlled trial examining the association of time to treatment (drug or placebo) with survival and neurological outcome. A secondary objective was to determine whether this relationship was modified by treatment type (i.e., amiodarone versus lidocaine). <h3>METHODS AND RESULTS</h3> In the ROC ALPS trial, adults with non-traumatic OHCA and an initial rhythm of shock refractory ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT) after at least one defibrillation were randomized to receive amiodarone, lidocaine, or placebo. We used logistic regression to examine the association of time to treatment (defined as a 911 call to study drug administration interval) with survival at hospital discharge and favourable neurological status at discharge (Modified Rankin Scale ≤ 3) for the three treatment groups. Time to treatment data were available for 2994/3026 (99%) of the patients. The proportion of patients who survived at hospital discharge decreased as time to drug administration increased in amiodarone (OR 0.91, 95% CI:0.90–0.93 per min increase in time interval), lidocaine (OR 0.93, 95% CI:0.91-0.96), and placebo (OR 0.91, 95% CI:0.90-0.93) treated patients. With short times to drug administration, survival was not different in lidocaine versus placebo, whereas survival was higher with lidocaine than placebo at later times after drug administration (Fig). The odds of survival at hospital discharge in the lidocaine group (as compared to placebo) changed significantly in relation to the time of drug administration in an adjusted analysis (OR 1.04, 95% CI:1.01-1.09, p=0.048). Comparing amiodarone to placebo, there was improved survival at discharge at all times of drug administration; there was no significant effect of time to drug administration (adjusted OR 1.00, 95% CI:0.95-1.03, p=0.84; unadjusted OR 0.99, 95% CI:0.95-1.03, p=0.67). Survival with good neurological outcome showed the same trends for all analyses. <h3>CONCLUSION</h3> In a post-hoc analysis of the ROC ALPS study, the probability of survival and favourable neurological outcomes decreased with a longer interval from a 911 call to receipt of amiodarone, lidocaine, or placebo. The effect of lidocaine but not amiodarone in increasing the probability of survival at hospital discharge and favourable neurological outcome varied based on the interval from 911 call to receipt of the drug.

Adherence of NSAID Administration in Patients with Mild and Moderate Traumatic Brain Injury in Dr. Soetomo General Hospital, Surabaya

Introduction: Traumatic brain injury (TBI) has a concerning incidence rate. One of the therapies for patients with TBI is non-steroidal anti-inflammatory drugs (NSAID) administration as an analgesic with proper adherence to achieve optimal therapy results. This research aimed to evaluate physicians’ NSAID administration adherence in patients with mild and moderate TBI in Dr. Soetomo General Hospital, Surabaya.Methods: This was an observational descriptive study with a retrospective design. NSAID administration adherence was graded by evaluating the dose, route, frequency, and interval of NSAID administration. The variables were evaluated by observing the medical records of inpatients with mild and moderate TBI from 1 January to 31 December 2018.Results: NSAIDs used for TBI management were metamizole, paracetamol, mefenamic acid, and ketorolac. Metamizole was administered in 10 patients (34.5%), paracetamol in 1 patient (3.4%), metamizole and paracetamol in 15 patients (51.7%), metamizole and mefenamic acid in 1 patient (3.4%), metamizole and paracetamol with mefenamic acid in 1 patient (3.4%), and metamizole and ketorolac in 1 patient (3.4%). Adherence of paracetamol, mefenamic acid, and ketorolac administration in patients with mild and moderate TBI were well-administered in every evaluated variable. Metamizole administration’s adherence was already well-administered in drug dosage and drug administration route, but it was not well-administered in drug administration interval and frequency.Conclusion: Physicians’ adherence to NSAID administration in patients with mild and moderate TBI in Dr. Soetomo General Hospital, Surabaya was well-administered, except for metamizole.

EVALUATION OF THE USE OF ANTIMALARIA MEDICINES IN HANURA HEALTH CENTRE PESAWARAN DISTRICT PERIOD JANUARY-DECEMBER IN 2018

Abstract Malaria is a public health problem in Indonesia, especially those living in isolated areas. This is published in Presidential Regulation No. 5/2010 concerning the National Medium Term Development Plan for malaria endemic areas, which are divided into high, medium and low endemic areas. High endemic if the API is greater than 50 out of 1,000 population in the provinces of Maluku, Papua, North Sumatra and East Nusa Tenggara. Moderate endemic if the API is 1 to less than 50 dari 1,000 population in the provinces of Aceh, Bangka Belitung, Jambi and West Nusa Tenggara. Low endemic if the API is 0-1 per 1,000 population in Kalimantan, Sulawesi, and parts of Java. This study aims to determine the evaluation of the use of antimalarial drugs with the characteristics of age, sex, and type of malaria plasmodium at the Hanura Public Health Centre based on the criteria of the right indication, the right drug, the right dose, the right interval of drug administration (4T). This research is a descriptive research with purposive sampling method. Collection of prescription data and medical records in January-December 2018. The results showed that in cases of Malaria based on age, the most common cases occurred in the age range of 56-65 years, amounting to 99.6%, based on sex experienced in men by 77.41%, based on body weight the most occurred at 41-59 kg at 45.16%, based on the type of plasmodium experienced plasmodium vivax mostly at 84.95%. Based on these data, it was concluded that the evaluation of the use of antimalarial drugs based on 4T criteria was 100% accurate indication, 100% correct drug, 72.04% correct dose, 98.92% correct interval of drug administration. Keywords: Malaria vivax, treatment, Puskesmas, 4T

A COMPARATIVE STUDY OF SUBLINGUAL, ORALAND VAGINAL ADMINISTRATION OF MISOPROSTOL IN THE MANAGEMENT OF MISSED ABORTION

Aim: A comparison of the efcacy of Misoprostol used in sublingual, oral and vaginal routes for missed abortion. A comparison of dose and time interval of drug administration to onset of action of three different routes. Material and methods: The study was conducted at the Department of Obstetrics and Gynaecology in Nilratan Sircar Medical College and Hospital, Kolkata after approval by the ethical committee. The sample size was 100 women being treated for missed abortions where prospective sampling was carried out to determine the candidates to be selected for the study. Single centred, institution based, randomized controlled trial. Cases included in this study were divided into 3 groups: Sublingual Group, Oral Group and Vaginal Group. Result: The mean Duration of induction to delivery time in hrs (mean±s.d.) of the patients was 14.0206 ± 1.4587 hr. In sublingual, the mean Duration of induction to delivery time in hrs (mean±s.d.) of patients was 9.3353 ± .8388 hr. In vaginal, the mean Duration of induction to delivery time in hrs (mean±s.d.) of patients was 10.4412 ± 1.2502 hr. Difference of mean Duration of induction to delivery time in hrs vs. group was statistically signicant (p&lt;0.001). Conclusion: Incomplete abortion was higher in oral, followed by Vaginal and Sublingual misoprostol. Success rate was higher in Sublingual compared to Vaginal and Oral.

A fluorescence biosensor for therapeutic drug monitoring of vancomycin using in vivo microdialysis

Clinical vancomycin (Van) treatment is administered over a prolonged period to achieve a sustained therapeutic effect. Accurate, rapid, and continuous Van detection is an unmet medical monitoring need that can provide data-based guidance for doctors to adjust the dosage and treatment plan in real-world settings. In this study, we created a Van-specific, fluorescent biosensor that was combined with a microdialysis sampling technique to develop a rapid, simple, accurate, and sensitive detection method, which was validated for Van in vivo. A Van-specific probe was created by separately conjugating each of the two peptide chains of a dimeric derivative of the Van binding peptide L-Lys-D-Ala-D-Ala to a fluorescent dansyl chloride group. Subject-specific pharmacokinetics of Van was recorded in normal rabbits and rabbits with adenine-induced chronic renal failure (CRF), which indicated the feasibility of therapeutic drug monitoring in vivo. The area under the concentration–time curve (AUC0–last) was 10,715 min μg mL−1 (95% CI = 8,892 to 12,538) in the normal rabbits, and 14,822 and 19,025 min μg mL−1 in two selected CRF rabbits. Furthermore, using pharmacokinetic dosing of Van in a rabbit study, we designed the dosage and drug administration interval to achieve a sustained therapeutic effect. The normal rabbits received three Van doses, 20, 5, and 5 mg kg−1, administered at 0, 500, and 900 min, respectively. The CRF rabbits received two Van doses, 20 and 5 mg kg−1, administered at 0 and 600 min, respectively. Thus, we established an effective method for the continuous monitoring of Van. This method facilitates the detection of Van in clinical treatment and provides the scientific basis for an effective approach to monitor blood drug levels during the clinical treatment of various diseases.

Teprotumumab in Clinical Practice: Recommendations and Considerations From the OPTIC Trial Investigators.

Background:Thyroid eye disease (TED) is a vision-threatening and debilitating condition that until very recently had no Food and Drug Administration (FDA)-approved medical therapies. Teprotumumab has recently been approved to treat TED. We aim to provide guidance for its use, based on the input of the US investigators who participated in Phase 2 and Phase 3 clinical trials.Methods:An expert panel was convened on October 11th and November 16th of 2019. All panel members had extensive experience as investigators in the Phase 2 and/or Phase 3 clinical trials of teprotumumab. Consensus among those investigators was reached to determine patient characteristics most appropriate for teprotumumab treatment. Safety guidelines were also reviewed and agreed on.Results:The authors recommend that teprotumumab be considered first-line therapy for patients with clinically significant ophthalmopathy, including those with disease duration exceeding 9 months. The clinical activity score (CAS) may be useful for longitudinal monitoring but should not be used to determine treatment eligibility. Criteria will likely be expanded after more experience with the drug. Using teprotumumab for patients with TED with substantial signs, symptoms, or morbidity without a CAS score of >4 (e.g., progressive proptosis, diplopia, and early compressive optic neuropathy) or more, could be considered. Diabetes mellitus and inflammatory bowel disease comorbidities should not be exclusionary, but stringent monitoring in these patients is recommended. Drug dosing, administration interval, and duration should adhere to the study protocol: 8 infusions, separated by 3 weeks. Patients with more severe disease may benefit from additional doses. Corticosteroids can be used before or during teprotumumab therapy. Clinical and laboratory monitoring should be consistent with good clinical practice for patients receiving teprotumumab.Conclusions:Confirming the efficacy of teprotumumab usage outside the narrow parameters of the completed clinical trials will require rigorous scientific validation. As a step in that direction, we believe its on-label usage is appropriately applied to all patients with TED with substantial symptoms or morbidity, as judged by their physician.

PHARMACIST INTERVENTION ON THE INCIDENCE OF DRUG RELATED PROBLEMS IN PATIEN WITH CHRONIC KIDNEY DISEASE IN RSU PKU MUHAMMADIYAH BANTUL

&lt;pre&gt;Chronic kidney disease (CKD) is a disease that often appears in various countries. Progressive decline in kidney function in patients with chronic kidney disease can lead to unexpected events from drug use, due to decreased kidney function in excreting the drug and its metabolites in addition to the co-morbidities that often arise. Drug Related Problems (DRPs) is one of the problems that can arise from a treatment. Drug Related Problems (DRPs) in addition to impacting the effectiveness and safety of a treatment can also cause morbidity, mortality and treatment costs incurred by the patient. This study aims to look at the picture of DRPs that occur in CKD patients and the effect of pharmacist intervention on DRPs in PKU Muhammadiyah Hospital Bantul by comparing DRPs that arise before and after pharmacist intervention. This research is descriptive with an observational cohort design. Data was collected prospectively in a cohort to see DRPs drawings and the influence of pharmacist interventions on the incidence of DRPs in inpatient CKD patients at PKU Muhammadiyah Hospital in Bantul in the period August-October 2017. The DRPs category followed the PCNE V7.0 DRP classification, recorded DRPs in the problem category for 19 cases (45.2%) and the category of loading were 24 cases (57.1%). The most drug related problems were found to be non-optimal therapy (28.6%), the time / interval of drug administration (26.8%), the combination of drugs with drugs (16.7%) and there were indications of no drugs (11.9% ). Pharmacists intervened with the incidence of DRPs found, pharmacists intervened in the form of changing instructions for using drugs (30.7%), giving information / recommendations to prescribers (16.7%) and providing education to patients (11.9%). Pharmacist intervention can prevent or overcome the DRPs found. Conclusions in this study there are still DRPs that occur in inpatient CKD patients. The involvement of pharmacists can prevent or reduce the incidence of DRPs and ensure efficient, effective and safe drug therapy.&lt;/pre&gt;

Carbapenems Utilization Evaluation in Neutropenic Patients of a Teaching Hospital

Background: Carbapenems is frequently prescribed for treatment or prophylaxis in neutropenic patients. It is cleared that antimicrobial misuse can cause poor patient outcomes, through raise of antibiotic resistance, increased adverse events, and prolonged length of hospital stay. To evaluate the rational use of Imipenem- Cilastatin and Meropenem for empirical antibacterial therapy in neutropenic patients based on IDSA guideline. Methods: Through this cross-sectional study, we assessed the appropriateness of administration of Carbapenems in neutropenic patients admitted in hematology–oncology and bone marrow transplant wards in Namazee hospital, Shiraz, Iran, from March 2012 to May 2013. Results: Total of 90 patients was enrolled. Drug therapy duration was appropriate in 69.6% of Imipenem-Cilastatin and 75% of Meropenem groups. Sampling time of culture was appropriated in 59.1% of Imipenem-Cilastatin and 78.3% of Meropenem group, interval of drug administration was correct in 74.5% at initiation and 79.4% during therapy in Imipenem-Cilastatin group. For dosing these values were 74.5% and 72.2%, respectively. These values were evaluated in patients who received Meropenem too, interval was correct in 89.5% at initiation and 90.3% during therapy, dosing was correct in 12.3% both at initiation and during therapy. Conclusion: These finding suggest that attention to correct dose, correct interval, renal dose adjustment, logical indication for administration of Carbapenem should be considered by health care system. J Pharm Care 2019; 7(4): 106-111.

The Rationality of Antibiotics Use on Inpatient Department of Pediatric in One of the Hospital in Cimahi

The purpose of this study is to assess the rationality of the use of antibiotics from inpatients in one hospital in Cimahi, West Java. The research about rationality analysis of antibiotics at pediatric inpatient in one of the hospitals in Cimahi was done retrospectively use descriptive analysis design. The data source was the medical record of a patient who treated at the children's inpatient ward from January through March 2017. The result shows that 39% of infected patients were children under one-year-old. Three significant cases of diseases that occurred in the period were bronchopneumonia, typhoid fever, and typhoid fever+bronchopneumonia. Antibiotics therapy was given as single therapy as well as combination, where cefotaxime (51%) and ceftriaxone (42%) were the most antibiotics widely used as single therapy. Antibiotic use at children inpatient ward during the period January � March 2017 on bronchopneumonia, typhoid fever, and typhoid fever + bronchopneumonia patients was not 100% rational referring to criteria: correct diagnosis, correct indication, the correct drug of choice, correct dosage, correct method, and correct time interval of drug administration.

Usefulness of a pharmacist outpatient service for S-1 adjuvant chemotherapy in patients with gastric cancer.

S-1 adjuvant chemotherapy is an outpatient treatment for gastric cancer. To evaluate the role of the pharmacist outpatient service in increasing medication adherence and reducing adverse events associated with S-1, the present study retrospectively analyzed prescription recommendations from pharmacists to physicians and the persistence rate of S-1 adjuvant chemotherapy use in patients with gastric cancer. A total of 40 subjects who utilized the pharmacist outpatient service between November 2014 and March 2016 comprised the pharmacist group; and 94 patients who underwent S-1 adjuvant chemotherapy for gastric cancer between September 2012 and October 2014, but not as pharmacist outpatients, comprised the control group. Data on the prescription recommendations, persistence rate of S-1 adjuvant chemotherapy for 1 year and relative dose intensity were collected. The number of interventions and consultations for the pharmacist outpatient group were 40 and 644, respectively. Prescription recommendations regarding dosage, drug administration interval, and supportive therapy were provided in 62, 15 and 132 cases, respectively. The prescription proposal acceptance rate was 92.5%. The persistence rate of S-1 adjuvant chemotherapy for 1 year was significantly higher in the pharmacist group (82.5%) compared with the control group (39.4%; P<0.0001). The discontinuation rate due to adverse events was significantly lower in the pharmacist group (7.5%) compared with the control group (31.9%; P=0.0015). In subjects who completed S-1 adjuvant chemotherapy, the relative dose intensities in the control and pharmacist groups were 82.9 and 84.7%, respectively. In conclusion, the continued pharmaceutical intervention ensured a high persistence rate of S-1 adjuvant chemotherapy.

Can intravenous steroid administration reduce postoperative pain scores following total knee arthroplasty?: A meta-analysis.

Background:The purpose of this systematic review and meta-analysis of randomized controlled trials (RCTs) was to evaluate whether intravenous steroids would result in reduced acute pain and postoperative nausea and vomiting (PONV) among patients undergoing total knee arthroplasty (TKA).Methods:Electronic databases, including PubMed, Embase, Web of Science, and the Cochrane Library, were searched to identify articles published from database inception to July 2016. RCTs that compared the effects of intravenous steroids with the effects of placebo among patients undergoing TKA were included in this meta-analysis. The primary outcomes were visual analogue scale (VAS) scores after 12, 24, and 48 hours of rest and PONV incidence. The secondary outcomes were blood glucose levels and incidence of infection. We calculated the risk ratio (RR) with its corresponding 95% confidence interval (CI) for dichotomous outcomes and the mean difference (MD) with its corresponding 95% CI for continuous outcomes.Results:Seven clinical trials involving 434 patients were included in the final meta-analysis. The pooled results indicated that intravenous steroids were associated with decreased VAS scores after 24 hours (MD = −10.21, 95%CI = −18.80 to −1.63, P = .020) and 48 hours (MD = −2.60, 95%CI = −4.70 to −0.50, P = .015) of rest. Moreover, intravenous steroids were also associated with decreased risk of nausea (RR = 0.58, 95% CI 0.44–0.77, P = .000) and vomiting (RR = 0.46, 95% CI = 0.24–0.88, P = .019). However, intravenous steroids were also associated with increased blood glucose levels. No significant difference in the risk of infection was identified between the 2 groups.Conclusion:Intravenous steroids may be associated with decreased pain intensity and decreased risk of nausea and vomiting during the early period following TKA. However, evidence supporting its use is limited by the low quality of and variations in dosing regimens between the included RCTs. Thus, more high-quality RCTs are needed to identify the optimal drug administration intervals for maximal pain control.

The Safety Profile of Single Daily Dose of Aminoglycosides in Comparison with Multiple Daily Dose

To overcome the problems which associated with the standard multiple daily doses (MDD)&#x0D; of aminoglycosides (AGs) like high incidence of toxicity(nephrotoxicity, ototoxicity)(5-25%) and high cost, an alternative approach was developed which was single daily dose (SDD).This new regimen was designed to maximize bacterial killing by optimizing the peak concentration/minimum inhibitory concentration(MIC)ratio and to reduce the potential for toxicity. The study includes 75 patients selected randomly, 50 of them received SDD regimen of age range of 17-79 years and the remaining received MDD regimen of age range of 13-71 years. The study was designed to evaluate the safety of SDD regimen in comparison with MDD regimen. All the patients in SDD group received a constant dose of 5-mg/kg/day of gentamicin and 20mg/kg/day of amikacin with a drug administration interval based on estimated creatinine clearance(CLcr): if ≥60 ml//min every 24 hours (q24h), 59- 40 ml/ min every 36hours and 39- 30 ml/min every 48 hours.The calculated dose was diluted with 0.9% normal saline or 5% dextrose to 50-100 ml and given as intravenous infusion over 30-60 minutes. In SDD group , the mean length of therapy was 6.4±1.73 days .Gentamicin accounted for 96% of the aminoglycoside use, and the majority(58%) of patients received the drug every 24 hours.The 36- and -48 hours intervals were used for 34 and 8% of the population, respectively.While in MDD group , the mean length of therapy was 5.0±0.91 days. Gentamicin accounted for all (100%) of aminoglycoside use, and all of the patients received the drug every 8 hours. No clinically apparent ototoxicity and nephrotoxicity were observed in the patients in the SDD group, in contrast to the patients in MDD group, in whom 4 patients (16%) were developed nephrotoxicity and 1 patient (4%) was developed ototoxicity. The obtained results indicate that SDD regimen was safer through decreasing the incidence of both nephrotoxicity and ototoxicity.For statistical analysis, ANOVA test was used with P&lt;0.01.Each mean was expressed as mean±SEM(Standard Error of Mean).&#x0D; Key words: Aminoglycosides, Single Daily Dose, Nephrotoxicity and Ototoxicity.

Longterm Beneficial Effect of Canakinumab in Colchicine-resistant Familial Mediterranean Fever.

To assess the efficacy and safety of the interleukin-1β (IL-1β) inhibitor canakinumab in all adolescent and adult patients with familial Mediterranean fever (FMF) identified from the Greek National Registry for off-label drug use between 2010 and 2015. In this retrospective longitudinal outcome study, clinical and laboratory data were collected from 14 patients (7 men) aged median 38.5 years (range 13-70), with median disease duration of 14 years, and active FMF despite colchicine (n = 9) or both colchicine and anakinra (n = 5). All patients continued to receive canakinumab at last visit (median of 18 mos, range 13-53), which was initially given as monotherapy (n = 8) or in combination with colchicine and/or corticosteroids, every 4 (n = 7), 6 (n = 2), or 8 weeks (n = 5). Eleven patients (79%), including 6 receiving monotherapy, achieved complete clinical remission within 2 months (median), while normalization of all laboratory variables denoting inflammation occurred in 92% at 3 months (median). The remaining 3 patients achieved partial responses. Responses were sustained in all but 4 patients, who relapsed. Reducing the canakinumab administration interval from 8 or 6 weeks to 4 weeks led to suppression of disease activity in the relapsing patients. On the other hand, drug administration interval could be safely increased in 2 patients in remission. Corticosteroid doses were significantly reduced during followup. Canakinumab was well tolerated; 1 patient experienced a urinary tract infection and another one a viral gastroenteritis. Treatment with canakinumab in an individualized dosing scheme results in rapid and sustained remission in colchicine-resistant FMF.

Drug price index of Beijing and the statistical analysis

Leveraging the centralized drug purchase platform of medical institutions in Beijing, the study measured the drug price index (DPI) and the DDD price index from 2005 to 2013, and the outcomes indicate a drop of both the drug price index and the drug price index calculated by DDD. Despite such drops however, drug price drop by itself could not curb the constant rise of drug expenses and medical costs due to changes in the structure and interval of drug administration. Key words: Drug; Price index; Drug expense; Beijing

Progress and problems in oral bisphosphonate

Oral bisphosphonates are the first class of drugs other than estrogen that have been proven to reduce fracture incidence substantially. Since they are agents that inhibit bone resorption and are hardly absorbed through intestine, researchers have been focusing on augmentation of inhibitory effects of bisphosphonates on bone resorption and prolongation of the interval of drug administration. Even though they have a break-through efficacy on preventing fractures, there remain some rare problems to be solved, such as osteonecrosis of the jaw and atypical femoral fracture, after long-term exposure to bisphosphonates.

The identification of a novel splicing mutation in C1qB in a Japanese family with C1q deficiency: a case report

C1q deficiency is a rare disease that is associated with a high probability of developing systemic lupus erythematosus. We report a 4-year-old Japanese girl who presented with fever, facial erythema, joint pain, and oral ulceration. Complement deficiencies were suspected because of her persistent hypocomplementemia and normal levels of the complement proteins C3 and C4. We identified a novel homozygous splicing mutation in the C1qB gene, c.187 + 1G > T, which is the first mutation to be confirmed in a Japanese individual. Because treatment with steroids and immunosuppressive drugs was not effective, we commenced use of fresh frozen plasma to provide C1q supplements. Currently, the patient remains almost asymptomatic, and we are attempting to control the drug dosage and administration intervals of fresh frozen plasma.

THU0189 Therapeutic Drug Monitoring (TDM) in Rheumatic Day Clinic Enables to Reduce Pharmaceutical Cost Maintaining Clinical Efficacy

BackgroundIn clinical practice of patients with rheumatic diseases, the optimization of the biological therapy (BT) is performed by adjusting drug dose according to clinical activity. To help taking accurate treatment...