Hydroxyethyl Starch 6% 130/0.4 in a Balanced Electrolyte Solution and Renal Function After Nephrectomy.

BACKGROUND: Although previous studies have reported nephrotoxicity associated with hydroxyethyl starch (HES), the long-term effect of HES on renal function after nephrectomy has rarely been reported. We evaluated the association between intraoperative HES administration and short- and long-term renal function after nephrectomy. METHODS: We retrospectively reviewed 1106 patients who underwent partial or radical nephrectomy. The patients were divided into 2 groups: patients who received (HES group) or did not receive 6% HES 130/0.4 intraoperatively (non-HES group). The primary outcome was new-onset chronic kidney disease (CKD) stage 3a (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m) or higher or all-cause mortality during 60 months after surgery. Propensity score matching was performed to address baseline differences between the 2 groups. Renal survival determined by stage 3a and stage 5 CKD (eGFR <15 mL/min/1.73 m) or all-cause mortality were compared up to 60 months before and after matching. We compared postoperative acute kidney injury (AKI) and CKD upstaging in the matched cohort as secondary outcomes. Ordinal logistic regression and Cox proportional hazards regression analyses using inverse probability of treatment weighting were performed for postoperative AKI and our primary outcome, respectively. A subgroup analysis of partial nephrectomy was performed. RESULTS: Thirty percent of patients received HES intraoperatively. Balanced solution and 0.9% normal saline was administered during surgery in both groups. Renal survival was not significantly different between groups after matching (log-rank test P = .377 for our primary outcome, and P = .981 for stage 5 or all-cause mortality, respectively). In the matched cohort (HES group: n = 280, non-HES group: n = 280), the incidence of AKI or CKD upstaging at 1 year was not significantly different (AKI: n = 94, 33.6% in HES group versus n = 90, 32.1% in non-HES group; CKD upstaging: n = 132, 47.1% in HES group versus n = 122, 43.6% in non-HES group; odds ratio [OR], 1.16; 95% confidence interval [CI], 0.83-1.61; P = .396). Intraoperative HES administration was not associated with postoperative renal outcomes (AKI: OR, 0.97; 95% CI, 0.81-1.16; P = .723; CKD stage 3a or higher or all-cause mortality: hazard ratio, 1.01; 95% CI, 0.89-1.14; P = .920). Subgroup analysis yielded similar results. CONCLUSIONS: Intraoperative 6% HES 130/0.4 administration was not significantly associated with short- and long-term renal function or renal survival up to 5 years in patients undergoing partial or radical nephrectomy. However, wide CI including large harm effect precludes firm conclusion and inadequate assessment of safety cannot be ruled out by our results.

Ciprofloxacin/dexamethasone precipitate formation in the ear canal of a paediatric patient.

This case report describes a paediatric patient diagnosed with otitis externa and treated with topical ciprofloxacin/dexamethasone. The patient completed the course of therapy and then developed precipitate formation from the pharmacological treatment. Laboratory testing of the precipitate confirmed the presence of a large quantity of ciprofloxacin. Removal of the precipitate required the use of an elephant ear washer system and removal with surgical tweezers. This case report investigated a probable topical ciprofloxacin/dexamethasone-induced ear precipitate formation in the ear canal, which, subsequently, was successfully removed from the patient's ear canal.

Calidad de la preparación para la colonoscopia en un entorno de práctica clínica privada / The quality of colonoscopy preparation in a private clinical practice setting

No disponible

Preclinical safety assessment of antipyrine combined with lidocaine hydrochloride as ear drops.

This study was designed to assess the preclinical toxicity of antipyrine combined with lidocaine hydrochloride ear drops (ALED) and support the clinical trials of ALED in clinical settings in China. All the experiments including acute toxicity in rodents, skin sensitization toxicity in guinea pigs, skin irritation toxicity in rabbits and chronic toxicity in rats were performed according to China Food and Drug Administration guidelines. The maximum tolerated dose (MTD) of ALED administration for mice and rats was over (400 g antipyrine plus 100 g lidocaine hydrochloride)/kg and (240 g andtipyrine plus 60 g lidocaine hydrochloride)/kg, respectively. No obvious skin sensitization toxicity and skin irritation toxicity were observed. The main changes concentrated in chronic toxicity study in rats. For the chronic toxicity, rats were administrated once a day for 28 consecutive days, and a 14-day recovery period was followed. The side effects of ALED included decreased dietary intake in male rats, increased proportion of reticulocytes, decreased or even inversed granulocyte:erythrocyte ratio, fluctuated alanine aminotransferase and aspartate aminotransferase, and slightly increased relative weight of liver. Conclusively, blood system (especially erythrocyte system) and digestive system, including liver and gastrointestinal tract, might be the toxic targets of ALED.

Comparison of administration of platelet concentrates suspended in M-sol or BRS-A for pediatric patients.

BACKGROUND: Two different platelet additive solutions (PASs), M-sol and BRS-A, used in succession, have been reported as novel PASs in Japan. However, there are not enough clinical data comparing platelet concentrates (PCs) suspended in these PASs. STUDY DESIGN AND METHODS: A retrospective cohort study of consecutive cases was performed between 2013 and 2018. For the first 30 months, children with primary hematologic and/or malignant diseases were transfused resuspended PCs in M-sol (RPC-M) as plasma-replaced PCs. For the subsequent 30 months, children were transfused plasma-replaced PCs in BRS-A (RPC-B) under the same conditions. Children transfused with conventional PCs (containing residual plasma) were defined as controls. We evaluated the frequency of adverse events, corrected count increment (CCI), and bleeding occurrence in the children. RESULTS: Overall, 84 patients received 679 conventional PC transfusions. Allergic transfusion reactions (ATRs) occurred in 12 (14.3%) patients transfused with 12 (1.8%) bags. Fifty-nine patients received a total of 1182 bags of RPC-M, and one patient (1.7%) had five (0.4%) ATR episodes. During the last 30 months, 58 patients were transfused 1044 bags of RPC-B, with ATRs occurring in four (6.9%) patients transfused with four (0.4%) bags. No other adverse events were observed with either RPC-M or RPC-B. CCIs (24 hr) were not significantly different for the three different PCs, and posttransfusion bleeding was not observed. CONCLUSIONS: Plasma-replaced PC using two different PAS in children appeared to prevent ATRs accompanied without other adverse events in children. Transfusion efficacy was not significant; therefore, either of the PASs could be used with equivalent results based on the clinical situation.

Choice of fluid type: physiological concepts and perioperative indications.

The consensus that i.v. resuscitation fluids should be considered as drugs with specific dose recommendations, contraindications, and side-effects has led to an increased attention for the choice of fluid during perioperative care. In particular, the debate concerning possible adverse effects of unbalanced fluids and hydroxyethyl starches resulted in a re-evaluation of the roles of different fluid types in the perioperative setting. This review provides a concise overview of the current knowledge regarding the efficacy and safety of distinct fluid types for perioperative use. First, basic physiological aspects and possible side-effects are explained. Second, we focus on considerations regarding fluid choice for specific perioperative indications based on an analysis of available randomized controlled trials.

Errors detected in pediatric oral liquid medication doses prepared in an automated workflow management system.

PURPOSE: The effectiveness of barcode-assisted medication preparation (BCMP) technology on detecting oral liquid dose preparation errors. METHODS: From June 1, 2013, through May 31, 2014, a total of 178,344 oral doses were processed at Children's Mercy, a 301-bed pediatric hospital, through an automated workflow management system. Doses containing errors detected by the system's barcode scanning system or classified as rejected by the pharmacist were further reviewed. Errors intercepted by the barcode-scanning system were classified as (1) expired product, (2) incorrect drug, (3) incorrect concentration, and (4) technological error. Pharmacist-rejected doses were categorized into 6 categories based on the root cause of the preparation error: (1) expired product, (2) incorrect concentration, (3) incorrect drug, (4) incorrect volume, (5) preparation error, and (6) other. RESULTS: Of the 178,344 doses examined, 3,812 (2.1%) errors were detected by either the barcode-assisted scanning system (1.8%, n = 3,291) or a pharmacist (0.3%, n = 521). The 3,291 errors prevented by the barcode-assisted system were classified most commonly as technological error and incorrect drug, followed by incorrect concentration and expired product. Errors detected by pharmacists were also analyzed. These 521 errors were most often classified as incorrect volume, preparation error, expired product, other, incorrect drug, and incorrect concentration. CONCLUSION: BCMP technology detected errors in 1.8% of pediatric oral liquid medication doses prepared in an automated workflow management system, with errors being most commonly attributed to technological problems or incorrect drugs. Pharmacists rejected an additional 0.3% of studied doses.

Efficacy and Safety of Once-Daily Minoxidil Foam 5% Versus Twice-Daily Minoxidil Solution 2% in Female Pattern Hair Loss: A Phase III, Randomized, Investigator-Blinded Study.

BACKGROUND: A once-daily minoxidil topical foam (MTF) has been developed to treat female pattern hair loss.
OBJECTIVE: Determine noninferiority of once-daily 5% MTF versus twice-daily 2% minoxidil topical solution (MTS) based on the change from baseline in target area hair count (TAHC) at 24 weeks. METHODS: In a randomized, phase III trial, women with female pattern hair loss received once-daily 5% MTF (n=161) or twice-daily 2% MTS (n=161) for 52 weeks. Primary endpoint was change from baseline in TAHC at 24 weeks. Secondary endpoint was change from baseline in TAHC at 12 weeks. Exploratory endpoints included change in total unit area density and change in overall scalp coverage.
RESULTS: Once-daily 5% MTF increased TAHC from baseline (adjusted mean ± standard error) by 23.9 ± 2.1 hairs/cm2 at week 24. Twice-daily 2% MTS increased TAHC 24.2 ± 2.1 hairs/cm2 at week 24. The treatment difference was -0.3 hairs/cm2 (95% CI = -6.0, 5.4). Since the lower bound of the 95% CI was less than -5.0, the prespecified noninferiority goal was not met. Both treatments were well tolerated.
CONCLUSIONS: Once-daily 5% MTF and twice-daily 2% MTS induced hair regrowth in female pattern hair loss, but prespecified noninferiority criteria were not met.
ClinicalTrials.gov identifier: NCT01145625

J Drugs Dermatol. 2016;15(7):883-889.

Microbial contamination of transplant solutions during pancreatic islet autotransplants is not associated with clinical infection in a pediatric population.

BACKGROUND/OBJECTIVES: Total pancreatectomy and islet autotransplant (TP-IAT) is a potential treatment for children with severe refractory chronic pancreatitis. Cultures from the resected pancreas and final islet preparation are frequently positive for microbes. It is unknown whether positive cultures are associated with adverse outcomes in pediatric patients. METHODS: We reviewed the medical records of children (n = 86) who underwent TP-IAT from May 2006-March 2015 with emphasis on demographics, previous pancreatic interventions, culture results, islet yield, hospital days, posttransplant islet function, and posttransplant infections. We compared outcomes in patients with positive (n = 57) and negative (n = 29) cultures. RESULTS: Patients with positive cultures had higher rates of previous pancreas surgery (P = 0.007) and endoscopic retrograde cholangiopancreatography (P < 0.0001). Positive cultures were not associated with posttransplant infections (P = 1.00) or prolonged hospital length of stay (P = 0.29). Patients with positive final islet preparation culture showed increased rates of graft failure at 2 years posttransplant (P = 0.041), but not when adjusted for islet mass transplanted (P = 0.39). CONCLUSIONS: Positive cultures during pediatric TP-IATs do not increase the risk of posttransplant infections or prolong hospital length of stay. Endocrine function depends on islet mass transplanted.

Pharmacokinetics, safety and tolerability of the novel, selective mineralocorticoid receptor antagonist finerenone - results from first-in-man and relative bioavailability studies.

The safety, tolerability and pharmacokinetics of the selective nonsteroidal mineralocorticoid receptor antagonist finerenone were evaluated in healthy male volunteers in two randomized, single-centre studies. Study 1 was a first-in-man, single-blinded, placebo-controlled, parallel-group, dose-escalation study. Fasted participants (n = 45) received single oral doses of finerenone 1-40 mg polyethylene glycol (PEG) solution or placebo. Study 2 was a relative bioavailability study comparing a finerenone 10 mg immediate-release (IR) tablet with finerenone 10 mg PEG solution in the fasted state, investigating the effect of a high-fat/high-calorie meal on the pharmacokinetics of the IR tablet and assessing a further dose escalation to finerenone 80 mg (eight × finerenone 10 mg IR tablets), in an open-label, fourfold crossover design (n = 15). Finerenone was rapidly absorbed from PEG solution (median time to maximum plasma concentration [tmax ]: 0.500-1.00 h), exhibited dose-linear pharmacokinetics and was rapidly eliminated from plasma (geometric mean terminal half-life [t½ ]: 1.70-2.83 h). Finerenone IR tablets demonstrated similar pharmacokinetics (median tmax : 0.750-2.50 h; geometric mean t½ : 1.89-4.29 h) with, however, enhanced bioavailability versus PEG solution (least-squares mean tablet/solution ratio of 187% for area under the plasma-concentration curve [AUC] and maximum plasma concentration [Cmax ]). High-fat/high-calorie food affected the rate but not the extent of finerenone absorption. Finerenone was well tolerated and did not influence clinical laboratory parameters, blood pressure, heart rate, urinary electrolytes or neurohormones, including serum aldosterone and angiotensin II. In conclusion, finerenone has favourable pharmacokinetics and tolerability in healthy men, and is suitable for dosing independent of food intake.

[Medication errors with concentrated potassium intravenous solutions: Data of the literature, context and prevention]. / Erreurs médicamenteuses avec les solutés concentrés de potassium injectable: données de la littérature, état des lieux et prévention.

Accidental direct intravenous injection of a concentrated solution of potassium often leads to patient death. In France, recommendations of healthcare agencies to prevent such accidents cover only preparation and intravenous infusion conditions. Accidents continue to occur in French hospitals. These facts demonstrate that these recommendations are insufficient and ineffective to prevent such deaths, especially those occurring during a catheter flushing. This article reviews the measures able to reduce the number of accidents. Countries which removed concentrated ampoules from ward stocks observed a decrease of the number of accidental deaths. This withdrawal, recommended by the World Health Organization, is now part of standards in studies aimed at determining the safety of care in hospitals. However, removal alone is insufficient to eliminate the risk. The combination with other measures should be considered. These measures are the provision of a combination of diluted intravenous ready to use solutions, the promotion of the oral route with tablets and oral solutions for potassium replenishment and to make available products with safeguards to prevent single shot intravenous injection. Studies aimed at determining the consequences on preventing concentrated potassium accidents of a widespread distribution of isotonic sodium chloride pre-filled ready-to-use syringes for catheter flushing should be performed.

Iatrogenic retinal breaks caused by infusion fluid during pars plana vitrectomy.

OBJECTIVE: To describe a series of cases of iatrogenic retinal breaks (IRBs) caused by the infusion fluid flow of a 25-gauge pars plana vitrectomy (PPV) system. DESIGN: Retrospective case series. METHODS: During 25-gauge PPV, 4 cases had IRBs caused by infusion fluid flow. The IRBs rapidly progressed to localized retinal detachment. RESULTS: The first 3 cases had IRBs on the nasal quadrant midperiphery of the retina. The IRBs were treated with laser retinopexy and tamponade during surgery. Case 4 had a macular hole and macular detachment during scleral indentation. The IRBs seemed to be caused by intraocular pressure (IOP) control mechanisms of the vitrectomy device. CONCLUSIONS: To prevent IRBs caused by infusion fluid flow, we recommend using an IOP control limit of 4 mL/min for 25-gauge vitrectomy, with valved cannulas. In addition, the surgeon must be cautious during scleral indentation and air-fluid exchange not to cause a rebound hypotonia.

Comparative evaluation of cariogenic and erosive potential of commonly prescribed pediatric liquid medicaments: an in vitro study.

INTRODUCTION: Liquid oral medicines being the most accepted form of medication in children are frequently prescribed. The harmful effects of these liquid medicaments on a child's dental health are not known to many. The present study aimed to evaluate and compare the cariogenic and erosive potential of 5 most commonly prescribed pediatric liquid medicaments (PLM) in Pimpri Chinchwad and Pune city, Pune district. MATERIALS AND METHODS: Most commonly prescribed PLM in Pune district were selected as opined by 50 pediatricians. The selected medicaments were Syr. Augmentin® Duo, Syr. Valparin®, Syr. Combiflam®, Syr. Visyneral and Syr. Orofer®. An estimation of pH, percentage of sucrose concentration and calcium dissolving capacity of these preparations was carried out. The results as obtained were subjected to statistical analysis using SPSS v 17.0 for windows. The statistical test as undertaken was Pearson's correlation coeffcient(r). RESULTS: Sucrose was seen to be present in Syr. Combiflam® (35.75% ± 0.25%) and Syr. Visyneral (18.48% ± 0.43%). Acidic pH was observed for Syr. Visyneral (mean pH 3.63 ± 0.04), Syr. Combiflam®(mean pH 5.03 ± 0.02) and Syr. Augmentin® (mean pH 6.22 ± 0.02). Highest calcium dissolution was seen with Syr. Combiflam®(295.86 mg/ml) and the least with Syr. Orofer® (25.51 mg/ml). No statistical significant correlation was observed with calcium dissolution potential of PLM in comparison with their respective pH. CONCLUSION: Syr. Combiflam® can be regarded as the highest cariogenic and erosive potential medicament among the compared and tested PLM. CLINICAL SIGNIFICANCE: Considering syrups with high cariogenic and erosive potential should always follow with proper oral hygiene practices or search for an alternative drugs void of such detrimental effects.

Erosive and cariogenicity potential of pediatric drugs: study of physicochemical parameters.

BACKGROUND: Pediatric medications may possess a high erosive potential to dental tissues due to the existence of acid components in their formulations. The purpose was to determine the erosive and cariogenic potential of pediatric oral liquid medications through the analysis of their physicochemical properties in vitro. METHODS: A total of 59 substances were selected from the drug reference list of the National Health Surveillance Agency (ANVISA), which belong to 11 therapeutic classes, as follows: analgesics, non-steroidal anti-inflammatory, corticosteroids, antihistamines, antitussives, bronchodilators, antibacterials, antiparasitics, antiemetics, anticonvulsants and antipsychotics. Measurement of pH was performed by potentiometry, using a digital pH meter. For the Total Titratable Acidity (TTA) chemical assay, a 0.1 N NaOH standard solution was used, which was titrated until drug pH was neutralized. The Total Soluble Solids Contents (TSSC) quantification was carried out by refractometry using Brix scale and the analysis of Total Sugar Content was performed according to Fehling's method. In addition, it was analyzed the information contained in the drug inserts with regard to the presence of sucrose and type of acid and sweetener added to the formulations. RESULTS: All drug classes showed acidic pH, and the lowest mean was found for antipsychotics (2.61 ± 0.08). There was a large variation in the TTA (0.1% - 1.18%) and SST (10.44% - 57.08%) values. High total sugar contents were identified in the antitussives (53.25%) and anticonvulsants (51.75%). As described in the drug inserts, sucrose was added in 47.5% of the formulations, as well as citric acid (39.0%), sodium saccharin (36.4%) and sorbitol (34.8%). CONCLUSION: The drugs analyzed herein showed physicochemical characteristics indicative of a cariogenic and erosive potential on dental tissues. Competent bodies' strategies should be implemented in order to broaden the knowledge of health professionals, drug manufacturers and general consuming public about the risks from the consumption of medicines potentially harmful to dental tissues.

Safety and tolerability of luliconazole solution 10-percent in patients with moderate to severe distal subungual onychomycosis.

The study objective was to evaluate the safety, tolerability, systemic exposure, and pharmacokinetics (PK) of 10% luliconazole solution (luliconazole) when topically applied once daily to all 10 toenails and periungual areas in patients with moderate to severe distal subungual onychomycosis. In this single-center, open-label study, 24 patients applied 20 mg/ml of luliconazole (twice the clinical dose) for 29 days with a 7-day follow-up. Complete PK profiles were determined on days 1, 8, 15, and 29. Safety/tolerability assessments included application site reactions, adverse events, vital signs, clinical laboratory findings, and electrocardiograms. Mean luliconazole plasma concentrations remained around the lower limit of quantitation (0.05 ng/ml) and were comparable on days 8, 15, and 29 (range, 0.063 to 0.090 ng/ml), suggesting steady state occurred by day 8. Every patient had undetectable plasma luliconazole levels for at least 11% of the time points, and 12 of the 24 patients had undetectable levels for at least 70% of the time points. The maximum plasma concentration of luliconazole (C(max)) observed in any patient was 0.314 ng/ml and the maximum area under the concentration-time curve from 0 to 24 h (AUC0-24) was 4.34 ng · h/ml. Five patients (21%) had measureable luliconazole levels in the plasma 7 days after the last dose. The median concentration of luliconazole in the nail at this time point was 34.65 mg/g (from 42 of 48 collected toenail samples). There was one mild incidence of skin erythema on day 5 that resolved on day 8, there were no reports of drug-induced systemic side effects, and there was no evidence of QT prolongation. Luliconazole, when applied once daily to all 10 fungus-infected toenails for 29 days, is generally safe and well tolerated and results in significant accumulation of drug in the nail. Systemic exposure is very low, with no evidence of drug accumulation.

High dosage of dextran 70 is associated with severe bleeding in patients admitted to the intensive care unit for septic shock.

INTRODUCTION: Synthetic colloids are frequently used in fluid resuscitation of septic patients. Despite this, little is known about the potential side effects including the risk of renal failure and bleeding. As practice has changed, we performed a before-and-after study of fluid resuscitation and outcome in patients with septic shock. MATERIAL AND METHODS: We retrospectively assessed all adult patients with septic shock admitted to a general intensive care unit (ICU) at a tertiary hospital in the years 2006 and 2008. Data on patient characteristics, resuscitation fluids in the ICU and outcome were collected from electronic databases and patient files. RESULTS: A total of 332 patients with septic shock were included: 171 in 2006 and 161 in 2008. The use of mainly dextran 70 in 2006 (median 3.5 (interquartile range 1.9-7.1) versus 1.5 (0.5-3.0) l, p < 0.0001; 44 (24-86) versus 18 (8-42) ml/kg, p < 0.0001) had changed to mainly crystalloids (Ringer's lactate 0 (0.0-0.3) versus 1.1 (0.0-3.0) l, p < 0.0001) and albumin (5%, 0.0 (0.0-1.0) versus 0.8 (0.0-1.5) l, p < 0.0001; 20%, 0.0 (0.0-0.3) versus 0.1 (0.0-0.4) l, p < 0.0001) in 2008. There were no differences in rates of renal replacement therapy or 90-day mortality, but more patients experienced severe bleeding in 2006 than in 2008 (30 versus 19%, p = 0.03). Also more red blood cells, plasma and platelets were given in 2006 than in 2008 (p < 0.01 for all). CONCLUSION: In patients with septic shock, fluid treatment had changed from mainly dextran 70 in 2006 to crystalloids and albumin in 2008. The administration of high-dosage dextran 70 was associated with more patients experiencing severe bleeding. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.