Irrigating Acetic Acid Solution During Colonoscopy for the Detection of Sessile Serrated Neoplasia: A Randomized Controlled Trial.

BACKGROUND: Misdiagnosed sessile serrated lesions (SSLs) are important precursors for interval colorectal cancers. AIMS: We investigated the usage of acetic acid (AA) solution for improving the detection of SSLs in the right colon in a randomized controlled trial. METHODS: A tandem observation of the right colon was performed in 412 consecutive patients. A first inspection was performed under white light high-definition endoscopy. In the AA group, a low concentration vinegar solution (AA: 0.005%) irrigated by a water pump in the right colon was compared with a plain solution of normal saline (NS) in the diagnostic yield of SSLs during the second inspection. Secondary outcomes in overall polyp detection were measured. RESULTS: Qualitative comparisons showed significant differences in the detection rates of all polyps except adenomas, with remarkable improvement in the demonstration of advanced (> 20 mm), SSLs, and hyperplastic polyps during the second inspection of the right colon using the AA solution. Significant improvement was also noted in the AA group, as far as the mean number of polyps/patient detected, not only in SSLs (AA group: 0.14 vs. NS group: 0.01, P < 0.001), but also in all histological types and all size-categories in the right colon. Small (≤ 9 mm) polyps were detected at a higher rate in the sigmoid colon expanding the effect of the method in the rest of the colon. CONCLUSION: AA-assisted colonoscopy led to a significant increase in SSLs detection rate in the right colon in a safe, quick, and effective manner.

Feasibility of developing children's Pill School within a UK hospital.

OBJECTIVE: We assessed the feasibility of introducing an intervention (children's Pill School-PS) within a UK hospital to provide swallowing training for children, identified the proportion of children who can be switched from oral liquid medicines to pills and assessed children/parents' opinions about the PS training. METHODS: 30 inpatient children (aged 3-18 years; taking oral liquid medicines; their liquid medications assessed suitable for switching to pills; can (and their parents) speak/understand English were included. Training sessions were delivered using hard sweets of different sizes. RESULTS: 87% (26) of children successfully learnt how to swallow pills after one training session (mean duration 14.5 min), and 92% (24) were discharged on pills. 75 prescribed oral liquid medications were deemed suitable for switching to pills. Of these, 89% (67) were switched successfully. CONCLUSION: Children as young as 3 years were successful in swallowing pills after training. Providing children PS training session within hospital is feasible and acceptable to children and their parents.

Relationships Between Pharmaceutical Therapy-Related Quality of Life and Health Utility Scores in Thai Patients With Chronic Diseases.

OBJECTIVES: The purpose of this study was to assess the relationships between pharmaceutical therapy-related quality of life (PTRQoL) and health utility (HU) scores since such data was not available. METHODS: The dataset of 1156 outpatients with chronic diseases from 3 public university hospitals in Bangkok, Thailand, were applied. The Patient-Reported Outcomes Measure of Pharmaceutical Therapy for Quality of Life (PROMPT-QoL) was utilized to assess PTRQoL. HU measures included EQ-5D-5L and EuroQoL-Visual Analog Scale (EQ-VAS). Multiple linear regressions using a stepwise approach were applied to evaluate the relationships between the PROMPT-QoL and the HU scores. RESULTS: The results found that the EQ-5D-5L was mostly correlated with the impacts of medicines and side-effects followed by the medicine effectiveness, psychologic impacts of medication use, and availability and accessibility domains of the PROMPT-QoL, respectively (actual R2 about 18%). The EQ-VAS was mostly associated with the impacts of medicines and side-effects, followed by the medicine effectiveness and overall quality of life domains, respectively (actual R2 about 14%). CONCLUSIONS: The PROMPT-QoL had medium correlations with the EQ-5D-5L and EQ-VAS scores. Their relationships depended on HU approaches used. More research is needed to examine the relationships between the PROMPT-QoL or other PTRQoL instruments and other HU scores in other settings and populations.

Effect of two different colloid priming strategies in infants weighing less than 5 kg undergoing on-pump cardiac surgeries.

Our aim was to explore the effect of two different priming strategies (artificial colloid only vs. artificial colloid combined with human serum albumin) on the prognosis of children weighing less than 5 kg undergoing on-pump congenital heart disease (CHD) surgery. A total of 65 children weighing less than 5 kg who underwent on-pump CHD surgery in our hospital from September 2016 to December 2017 were enrolled in this study. The children were randomly divided into two groups: artificial colloid priming group (AC group, n = 33) and artificial colloid combined albumin priming group (ACA group, n = 32). The primary clinical endpoint was the peri-CPB colloid osmotic pressure (COP). Secondary clinical endpoints included perioperative blood product and hemostatic drug consumption, postoperative renal function, coagulation function, postoperative renal function, and postoperative recovery parameters. COP values were not significant in the priming system as well as peri-CPB time points between the two groups (P > .05). Platelet consumption in the AC group was significantly lower than that in the ACA group (P < .05). There were no significant differences in the use of other blood products and hemostatic drugs as well as perioperative coagulation parameters between the two groups (P > .05). Postoperative length of stay in the AC group was significantly lower than that in the ACA group (P < .05). There were no significant differences in mortality, postoperative mechanical ventilation time, ICU time, and perioperative adverse events (including postoperative AKI) occurrences between the two groups (P > .05). In the on-pump cardiac surgeries of patients weighing less than 5 kg, total colloidal priming would not affect peri-CPB COP values, postoperative coagulation function, and blood products consumption. Total artificial colloidal priming strategy is feasible in low-weight patients.

The effect of three different solutions on preventing oral mucositis in cancer patients undergoing stem cell transplantation: a non-randomized controlled trial: A Turkish study - NON-RANDOMISED TRIAL.

OBJECTIVE: To evaluate the effect of different solutions administered to patients undergoing stem cell transplantation on oral mucositis. METHODS: The non-randomised controlled trial was conducted at a Istanbul Medipol Mega university hospital in Turkey between May 2014 and June 2016, and comprised patients undergoing stem cell transplantation. They were divided into three groups. Group 1 had patients using chlorhexidine gluconate and benzydamine hydrochloride solution. Group 2 had those using calcium and phosphate solution. Group 3 patients were using black mulberry syrup. Data was collected using a structured questionnaire and the World Health Organisation mucositis assessment scale. Assessment was done on days 7, 14 and 21. Clinical significance of oral solutions was statistically determined. RESULTS: Of the 83 patients, 30(36%) were in group 1, 28(34%) in group 2, and 25(30%) in group 3. On day 7, there was no significant difference in terms of grades among the groups (p>0.05). On day 14, grade 2 mucositis was seen in 2(8%) patents in group 3, 5(17.9%) in group 2 and 5(16.7%) in group 1; Grade 3 mucositis was seen in 2(6.7%) patients in group 1, but none in the other two groups. On day 21, grade 3 mucositis was present in 2(8.0%) in group 3, 2(7.1%) in group 2, and 4(13.3%) in group 1. CONCLUSIONS: The use of black mulberry and calcium-phosphate solutions was found to be beneficial in preventing and treating oral mucositis.

The Added Value of Liquid Antipsychotics: The Case of Quetiapine.

BACKGROUND: Antipsychotic drugs are the cornerstone of schizophrenia treatment and are also indicated for other psychotic and mood disorders. Different antipsychotic drugs and their formulations are available, though liquid forms have been overlooked. METHODS: Herein the added value of liquid antipsychotics is reviewed, with a focus on the recently introduced liquid quetiapine, a frequently used antipsychotic. RESULTS: Liquid antipsychotics are easily administrated via the preferable oral route, while compliance under supervised administration is transparent. Liquid forms could be preferred in patients with swallowing difficulties, which are common in elderly patients and often concealed. In this population, the availability of liquid antipsychotics could prevent errors in medication administration, which could possibly render caregivers labile to any harm caused to the patient. Aspiration, however, remains a risk with liquid formulations. Common errors in medication administration are the omission of treatment and alteration of solid oral formulations. Regarding quetiapine, omission of treatment could be associated with non-adherence as well as discontinuation symptoms, while alteration of extended release formulation could alter its pharmacokinetics. Mildly agitated and cooperative patients are another target population of liquid antipsychotics, which can induce fast sedation avoiding involuntary intramuscular injections. The combination of sedative properties and low incidence of extrapyramidal symptoms makes liquid quetiapine a valuable option for these patients, yet the current evidence is limited. CONCLUSION: The liquid form of quetiapine can facilitate pharmacotherapy of schizophrenia and can be defined as value added medicine bringing key benefits not only to the patients and caregivers but also to the health care system.

Efficacy of fluralaner plus moxidectin (Bravecto® Plus spot-on solution for cats) against Otodectes cynotis infestations in cats.

BACKGROUND: The efficacy of the fixed combination of fluralaner plus moxidectin for the treatment of Otodectes cynotis infestations was evaluated in cats after topical application. METHODS: Sixteen cats experimentally infested with O. cynotis were allocated randomly to two groups of 8 cats each. One group was treated topically with the fixed combination of fluralaner plus moxidectin at the minimum dose rate of 40 mg fluralaner and 2 mg moxidectin/kg body weight. The other group was treated with physiological saline solution. Before and 14 and 28 days after treatment the ears of all cats were examined otoscopically for live mites and for the amount of debris and cerumen. Twenty-eight days after treatment, the cats were sedated and had both ears flushed to obtain the total number of live mites per animal. Efficacy was calculated, based on the results of the ear flushing, by comparing mean live mite counts in the fluralaner plus moxidectin treated group versus the saline group. RESULTS: A single topical application of the fixed combination of fluralaner plus moxidectin to cats reduced the mean mite counts by 100% (P < 0.001) by 28 days after treatment. No mites were visible during otoscopic examination at either 14 or 28 days after treatment. All fluralaner plus moxidectin treated cats had less ceruminous exudate 28 days after treatment compared to pre-treatment and 14 days after treatment. No treatment related adverse events were observed in any cats enrolled in the study. CONCLUSIONS: Single topical application of the fixed combination of fluralaner plus moxidectin was highly effective against O. cynotis infestations in cats.

Biocompatible dialysis fluids for peritoneal dialysis.

BACKGROUND: Biocompatible peritoneal dialysis (PD) solutions, including neutral pH, low glucose degradation product (GDP) solutions and icodextrin, have previously been shown to favourably influence some patient-level outcomes, albeit based on generally sub-optimal quality studies. Several additional randomised controlled trials (RCT) evaluating biocompatible solutions in PD patients have been published recently. This is an update of a review first published in 2014. OBJECTIVES: This review aimed to look at the benefits and harms of biocompatible PD solutions in comparison to standard PD solutions in patients receiving PD. SEARCH METHODS: The Cochrane Kidney and Transplant Specialised Register was searched up to 12 February 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: All RCTs and quasi-RCTs in adults and children comparing the effects of biocompatible PD solutions (neutral pH, lactate-buffered, low GDP; neutral pH, bicarbonate(± lactate)-buffered, low GDP; glucose polymer (icodextrin)) in PD were included. Studies of amino acid-based solutions were excluded. DATA COLLECTION AND ANALYSIS: Two authors extracted data on study quality and outcomes. Summary effect estimates were obtained using a random-effects model, and results were expressed as risk ratios and 95% confidence intervals (CI) for categorical variables, and mean differences (MD) or standardised mean differences (SMD) and 95% CI for continuous variables. MAIN RESULTS: This review update included 42 eligible studies (3262 participants), including six new studies (543 participants). Overall, 29 studies (1971 participants) compared neutral pH, low GDP PD solution with conventional PD solution, and 13 studies (1291 participants) compared icodextrin with conventional PD solution. Risk of bias was assessed as high for sequence generation in three studies, allocation concealment in three studies, attrition bias in 21 studies, and selective outcome reporting bias in 16 studies.Neutral pH, low GDP versus conventional glucose PD solutionUse of neutral pH, low GDP PD solutions improved residual renal function (RRF) preservation (15 studies, 835 participants: SMD 0.19, 95% CI 0.05 to 0.33; high certainty evidence). This approximated to a mean difference in glomerular filtration rate of 0.54 mL/min/1.73 m2 (95% CI 0.14 to 0.93). Better preservation of RRF was evident at all follow-up durations with progressively greater preservation observed with increasing follow up duration. Neutral pH, low GDP PD solution use also improved residual urine volume preservation (11 studies, 791 participants: MD 114.37 mL/day, 95% CI 47.09 to 181.65; high certainty evidence). In low certainty evidence, neutral pH, low GDP solutions may make little or no difference to 4-hour peritoneal ultrafiltration (9 studies, 414 participants: SMD -0.42, 95% CI -0.74 to -0.10) which approximated to a mean difference in peritoneal ultrafiltration of 69.72 mL (16.60 to 122.00 mL) lower, and may increase dialysate:plasma creatinine ratio (10 studies, 746 participants: MD 0.01, 95% CI 0.00 to 0.03), technique failure or death compared with conventional PD solutions. It is uncertain whether neutral pH, low GDP PD solution use led to any differences in peritonitis occurrence, hospitalisation, adverse events (6 studies, 519 participants) or inflow pain (1 study, 58 participants: RR 0.51, 95% CI 0.24 to 1.08).Glucose polymer (icodextrin) versus conventional glucose PD solutionIn moderate certainty evidence, icodextrin probably reduced episodes of uncontrolled fluid overload (2 studies, 100 participants: RR 0.30, 95% CI 0.15 to 0.59) and augmented peritoneal ultrafiltration (4 studies, 102 participants: MD 448.54 mL/d, 95% CI 289.28 to 607.80) without compromising RRF (4 studies, 114 participants: SMD 0.12, 95% CI -0.26 to 0.49; low certainty evidence) which approximated to a mean creatinine clearance of 0.30 mL/min/1.73m2 higher (0.65 lower to 1.23 higher) or urine output (3 studies, 69 participants: MD -88.88 mL/d, 95% CI -356.88 to 179.12; low certainty evidence). It is uncertain whether icodextrin use led to any differences in adverse events (5 studies, 816 participants) technique failure or death. AUTHORS' CONCLUSIONS: This updated review strengthens evidence that neutral pH, low GDP PD solution improves RRF and urine volume preservation with high certainty. These effects may be related to increased peritoneal solute transport and reduced peritoneal ultrafiltration, although the evidence for these outcomes is of low certainty due to significant heterogeneity and suboptimal methodological quality. Icodextrin prescription increased peritoneal ultrafiltration and mitigated uncontrolled fluid overload with moderate certainty. The effects of either neutral pH, low GDP solution or icodextrin on peritonitis, technique survival and patient survival remain uncertain and require further high quality, adequately powered RCTs.

Ear drops for the removal of ear wax.

BACKGROUND: Ear wax (cerumen) is a normal bodily secretion that can become a problem when it obstructs the ear canal. Symptoms attributed to wax (such as deafness and pain) are among the commonest reasons for patients to present to primary care with ear trouble.Wax is part of the ear's self-cleaning mechanism and is usually naturally expelled from the ear canal without causing problems. When this mechanism fails, wax is retained in the canal and may become impacted; interventions to encourage its removal may then be needed. Application of ear drops is one of these methods. Liquids used to remove and soften wax are of several kinds: oil-based compounds (e.g. olive or almond oil); water-based compounds (e.g. sodium bicarbonate or water itself); a combination of the above or non-water, non-oil-based solutions, such as carbamide peroxide (a hydrogen peroxide-urea compound) and glycerol. OBJECTIVES: To assess the effects of ear drops (or sprays) to remove or aid the removal of ear wax in adults and children. SEARCH METHODS: We searched the Cochrane ENT Trials Register; Cochrane Register of Studies; PubMed; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the most recent search was 23 March 2018. SELECTION CRITERIA: Randomised controlled trials (RCTs) in which a 'cerumenolytic' was compared with no treatment, water or saline, an alternative liquid treatment (oil or almond oil) or another 'cerumenolytic' in adults or children with obstructing or impacted ear wax. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. The primary outcomes were 1) the proportion of patients (or ears) with complete clearance of ear wax and 2) adverse effects (discomfort, irritation or pain). Secondary outcomes were: extent of wax clearance; proportion of people (or ears) with relief of symptoms due to wax; proportion of people (or ears) requiring further intervention to remove wax; success of mechanical removal of residual wax following treatment; any other adverse effects recorded and cost. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics. MAIN RESULTS: We included 10 studies, with 623 participants (900 ears). Interventions included: oil-based treatments (triethanolamine polypeptide, almond oil, benzocaine, chlorobutanol), water-based treatments (docusate sodium, carbamide peroxide, phenazone, choline salicylate, urea peroxide, potassium carbonate), other active comparators (e.g. saline or water alone) and no treatment. Nine of the studies were more than 15 years old.The overall risk of bias across the 10 included studies was low or unclear. PRIMARY OUTCOME: proportion of patients (or ears) with complete clearance of ear waxSix studies (360 participants; 491 ears) contributed quantitative data and were included in our meta-analyses.Active treatment versus no treatmentOnly one study addressed this comparison. The proportion of ears with complete clearance of ear wax was higher in the active treatment group (22%) compared with the no treatment group (5%) after five days of treatment (risk ratio (RR) 4.09, 95% confidence interval (CI) 1.00 to 16.80); one study; 117 ears; NNTB = 8) (low-quality evidence).Active treatment versus water or salineWe found no evidence of a difference in the proportion of patients (or ears) with complete clearance of ear wax when the active treatment group was compared to the water or saline group (RR 1.47, 95% CI 0.79 to 2.75; three studies; 213 participants; 257 ears) (low-quality evidence). Two studies applied drops for five days, but one study only applied the drops for 15 minutes. When we excluded this study in a sensitivity analysis it did not change the result.Water or saline versus no treatmentThis comparison was only addressed in the single study cited above (active versus no treatment) and there was no evidence of a difference in the proportion of ears with complete wax clearance when comparing water or saline with no treatment after five days of treatment (RR 4.00, 95% CI 0.91 to 17.62; one study; 76 ears) (low-quality evidence).Active treatment A versus active treatment BSeveral single studies evaluated 'head-to-head' comparisons between two active treatments. We found no evidence to show that one was superior to any other.Subgroup analysis of oil-based active treatments versus non-oil based active treatmentsWe found no evidence of a difference in this outcome when oil-based treatments were compared with non-oil-based active treatments. PRIMARY OUTCOME: adverse effects: discomfort, irritation or painOnly seven studies planned to measure and did report this outcome. Only two (141 participants;176 ears) provided useable data. There was no evidence of a significant difference in the number of adverse effects between the types of ear drops in these two studies. We summarised the remaining five studies narratively. All events were mild and reported in fewer than 30 participants across the seven studies (low-quality evidence).Secondary outcomesThree studies reported 'other' adverse effects (how many studies planned to report these is unclear). The available information was limited and included occasional reports of dizziness, unpleasant smell, tinnitus and hearing loss. No significant differences between groups were reported. There were no emergencies or serious adverse effects reported in any of the 10 studies.There was very limited or no information available on our remaining secondary outcomes. AUTHORS' CONCLUSIONS: Although a number of studies aimed to evaluate whether or not one type of cerumenolytic is more effective than another, there is no high-quality evidence to allow a firm conclusion to be drawn and the answer remains uncertain.A single study suggests that applying ear drops for five days may result in a greater likelihood of complete wax clearance than no treatment at all. However, we cannot conclude whether one type of active treatment is more effective than another and there was no evidence of a difference in efficacy between oil-based and water-based active treatments.There is no evidence to show that using saline or water alone is better or worse than commercially produced cerumenolytics. Equally, there is also no evidence to show that using saline or water alone is better than no treatment.

The Management of Critically Colonized and Locally Infected Leg Ulcers with an Acid-Oxidizing Solution: A Pilot Study.

OBJECTIVE: Critical colonization or local infection is very common in chronic wounds, but clinically problematic. Because therapeutic options for these conditions are limited in number and efficacy, the study authors tested a new acid-oxidizing solution (AOS [Nexodyn]; APR Applied Pharma Research S.A., Balerna, Switzerland) to determine its ancillary antimicrobial properties and potential support for wound healing. DESIGN AND SETTING: This open-label clinical case series was conducted with a prospective, single-arm design at the Federal County Hospital in Bregenz, Austria. PATIENTS: In the study, 30 patients with critically colonized or locally infected chronic leg ulcers of any origin were included. INTERVENTIONS: The AOS was applied on each leg ulcer at every dressing change for 35 days. MAIN OUTCOME MEASURES: The tolerability and performance of the AOS were assessed by evaluating the ulcer characteristics and comparing them with those at baseline. The clinical course of wounds was analyzed using standard measures for bioburden, local infection, pain, pH, and wound healing. MAIN RESULTS: Application of the solution was well tolerated, and no adverse events were recorded. In all patients, local infection was overcome, and wound bed pH and wound area decreased significantly. In addition, patient pain levels decreased to a level where interventions were not required after study day 7. In 37% of all patients, a complete resolution of chronic ulcers was achieved by the end of the study period. CONCLUSION: According to these results, the AOS seems to be a valid and highly tolerable treatment to support wound healing in locally infected ulcers. Nevertheless, larger controlled cohort studies are needed to substantiate these findings.

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.

Plasma Concentration of Itraconazole in Patients With Hematologic Malignancies Treated With Itraconazole Oral Solution.

BACKGROUND: The prophylactic administration of itraconazole (ITCZ) is effective for preventing mycotic infections during chemotherapy in patients with hematologic malignancies. However, fungal infections can occur when the ITCZ does not reach an effective concentration. METHODS: We conducted a prospective study to monitor the plasma concentration of ITCZ and hydroxyl-ITCZ (OH-ITCZ) weekly and to verify whether the day 3 plasma concentration of ITCZ could predict the subsequent acquisition of an effective plasma concentration. RESULTS: A total of 39 patients who underwent 66 courses of chemotherapy were assessed in this study. An effective plasma concentration was achieved on day 7 in 34 of 63 patients (54%) and on day 14 in 35 of 59 patients (59%). A univariate analysis revealed that age, type of chemotherapy, and the body surface area were significantly associated with a high plasma concentration of ITCZ + OH-ITCZ. A linear regression analysis extracted the body surface area and the type of chemotherapy as significant factors. An receiver operating characteristic curve analysis revealed a day 3 plasma ITCZ + OH-ITCZ concentration of >656 ng/mL led to a plasma concentration that exceeded the minimum effective level on day 7; the sensitivity and specificity were 62% and 93%, respectively. CONCLUSIONS: This study showed that the measurement of the day 3 plasma concentration could lead to a better outcome in patients receiving chemotherapy for hematologic malignancies.

Efficacy and safety of luliconazole 5% nail solution for the treatment of onychomycosis: A multicenter, double-blind, randomized phase III study.

Onychomycosis is a highly prevalent and intractable disease. The first-line treatment agents are oral preparations, but an effective topical medication has long been desired. The objective was to investigate the efficacy and safety of luliconazole 5% nail solution, an imidazole antifungal agent, for the treatment of patients with onychomycosis. A multicenter, double-blind, randomized phase III study was conducted in Japanese patients with distal lateral subungual onychomycosis affecting the great toenails, with 20-50% clinical involvement. Patients were randomized (2:1) to luliconazole or vehicle once daily for 48 weeks. The primary end-point was the complete cure rate (clinical cure [0% clinical involvement of the nail] plus mycological cure [negative results on direct microscopy]). The adverse event incidence was monitored to evaluate safety. The complete cure rate significantly favored luliconazole (14.9%, 29/194 subjects) versus vehicle (5.1%, 5/99) (P = 0.012). Similarly, the negative direct microscopy rate was significantly higher with luliconazole (45.4%, 79/174) than with vehicle (31.2%, 29/93) (P = 0.026). There were no serious adverse drug reactions. We conclude that once daily topical luliconazole 5% nail solution demonstrated clinical efficacy and was confirmed to be well tolerated.

Optical coherence tomography analysis of hydrofluoric acid decontamination of human cornea by mannitol solution.

PURPOSE: To evaluate the efficacy of mannitol solution as a decontamination agent on the chemical burn of the human corneas. METHODS: Eight donor corneas from an eye bank were exposed to 25µl of 2.5% hydrofluoric acid (HF) solution on a filter paper for 20s. Three eyes were rinsed with 1000ml of mannitol 20% for 15min immediately after removal of the filter paper, 3 other were rinsed with sodium chloride (NaCl) 0.9% (1000ml for 15min) and two eyes were not rinsed. Microstructural changes were monitored in the time domain by optical coherence tomography (OCT) imaging for 75min. RESULTS: NaCl reduced the penetration depth to approximately half the thickness of the cornea at 15min; scattering within the anterior cornea was higher than that for the unrinsed eye. With mannitol, no increased scattering was observed in the posterior part of the corneal stroma within a time period of 1h after rinsing. OCT images revealed low-scattering intensity within the anterior stroma at the end of the rinsing period. CONCLUSION: In eye bank human corneas, mannitol proved to be an efficient agent to decontaminate HF burn.

The Influence of Polyethylene Glycol Solution on the Dissolution Rate of Sustained Release Morphine.

INTRODUCTION: Whole bowel irrigation (WBI) is a management option for overdose of medications poorly adsorbed to activated charcoal, with modified release properties, or for body packers. Polyethylene glycol (PEG) is a mixture of ethylene oxide polymers of varying molecular weight. PEG with an average molecular weight of 3350 g/mol is used for WBI. PEG electrolyte lavage solution has been shown in vitro to hasten the dissolution of acetaminophen. The impact of PEG on the pharmacokinetics of extended release pharmaceuticals is unknown. Lower average molecular weight PEG mixtures are used as solvents and excipients. We sought to investigate the impact of PEG on the release of morphine from several extended release morphine formulations. METHODS: An in vitro gastric model was developed. To test the validity of our model, we first investigated the previously described interaction of ethanol and Avinza®. Once demonstrated, we then investigated the effect of PEG with several extended release morphine formulations. RESULTS: In the validation portion of our study, we confirmed an ethanol Avinza® interaction. Subsequently, we did not observe accelerated release of morphine from Avinza® or generic extended release morphine in the presence of PEG. CONCLUSION: The use of PEG for gastric decontamination following ingestion of these extended release morphine formulations is unlikely to accelerate morphine release and aggravate intoxication.

Impacto de una intervención farmacéutica en la prevención de recaídas en depresión en atención primaria / Impact of pharmaceutical intervention in preventing relapses in depression in Primary Care

OBJETIVO: Evaluar el impacto a largo plazo de una intervención farmacéutica (IF) respecto a la atención habitual (AH) en la prevención de recaídas en depresión. DISEÑO: Ensayo clínico aleatorizado (estudio PRODEFAR). Emplazamiento: Atención primaria. PARTICIPANTES: Ciento setenta y nueve pacientes con depresión mayor que inician antidepresivos, de estos, se seleccionaron para este análisis secundario los 113 cuyos síntomas habían remitido (definición principal) a los 6 meses (grupo intervención [GI] = 58; grupo control [GC] = 55). Intervención: Se realizó una entrevista personal en la farmacia comunitaria para mejorar la adhesión terapéutica durante la dispensación de medicación. MEDICIONES PRINCIPALES: Se realizaron 3 mediciones (línea base, 3 y 6 meses). La gravedad de síntomas depresivos (PHQ-9) fue evaluada a los 6 meses y se seleccionaron aquellos pacientes que presentaban remisión. Se revisaron sus historias clínicas para identificar recaídas, mediante 4 indicadores, en los siguientes 12 meses. RESULTADOS: La proporción de recaídas (variable principal) fue menor en el GI respecto al GC a los 18 meses de haber iniciado el tratamiento, pero la diferencia no fue estadísticamente significativa, ni en análisis por intención de tratar (OR = 0,734 [IC 95% 0,273;1,975]) ni en el análisis por protocolo (OR = 0,615 [95% CI 0,183; 2,060]). Todos los análisis de sensibilidad mostraron resultados consistentes. El tamaño de la muestra y la adhesión al protocolo en el GI fueron bajos. CONCLUSIÓN: El GI mostró una tendencia no significativa a presentar un menor número de recaídas. Esto podría relacionarse con la mejora en la adhesión entre los pacientes que recibieron la IF

OBJECTIVE: To evaluate the long-term impact of a brief pharmacist intervention (PI) compared with usual care (UC) on prevention of depression relapse. DESIGN: randomised controlled clinical trial SETTING: Primary Care. PARTICIPANTS: Of the 179 depressed patients initiating antidepressants, the 113 whose clinical symptoms had remitted (main definition) at 6 months assessment were selected for this secondary study (PI = 58; UC = 55). Intervention: PI was an interview to promote medication adherence when patients get antidepressants from pharmacy. MAIN MEASUREMENTS: Baseline, 3 months, and six-months follow-up assessments were made. The severity of depressive symptoms was evaluated with PHQ9. Patients presenting a remission of symptoms were selected. The patient medical records were reviewed to identify a relapse in the following 12 months by using 4 indicators. RESULTS: There was a lower proportion of patients that relapsed in the PI group than in the UC group 18 months after initiation of treatment, but the difference was not statistically significant either in the intent-to-treat analysis (OR = 0.734 [95%CI; 0.273-1.975]) or the per-protocol analysis (OR = 0.615 [95%CI; 0.183 -2.060]). All the sensitivity analyses showed consistent results. The sample size and adherence to the protocol in the intervention group were low. CONCLUSION: PI group showed a non-statistically significant tendency towards presenting fewer relapses. This could be related to the improvement in adherence among patients that received the intervention

Inhalation Properties and Stability of Nebulized Naked siRNA Solution for Pulmonary Therapy.

The use of naked unmodified small interfering RNA (N-siRNA) without vector has previously been investigated as a pulmonary therapy. However, little is known regarding stabilities and aerodynamic particle sizes of N-siRNA-containing droplets; nebulizers have not yet been optimized for N-siRNA solutions. Thus, in this study, we investigated the feasibility of inhaled N-siRNA solutions for pulmonary therapy using nebulization. Various nebulizers and N-siRNA concentrations were assessed in terms of siRNA integrity after nebulization, and inhalation properties including aerodynamic particle size were examined. In comparison with ultrasonic-, air-jet-, and vibrating-mesh nebulizers, N-siRNA integrity was not affected by nebulization. Thus, in further experiments, performances of N-siRNA aerosols with different nebulizers and N-siRNA concentrations were evaluated and screened using an aerodynamic particle sizer (APS) which employed the time-of-flight principle or a cascade impactor. Mean mass aerodynamic diameters of N-siRNA-containing droplets from vibrating-mesh nebulizers tended to decrease with increasing N-siRNA concentrations, reflecting the influence of N-siRNA solutions on surface tension, as indicated by contact angles. These data indicate the utility of APS instruments for investigating the nebulized characteristics of expensive drugs including siRNAs and may facilitate the development of N-siRNA inhalation formulations.

IgM-enriched solution BT086 improves host defense capacity and energy store preservation in a rabbit model of endotoxemia.

INTRODUCTION: The therapeutic value of intravenous immunoglobulin (IVIG) as an adjuvant therapy in sepsis remains debatable. We hypothesized that intravenous administration of BT086, a predominantly IgM IVIG solution, would improve host defense in an established rabbit model of endotoxemia and systemic sepsis. METHODS: New Zealand white rabbits were randomized into the following four groups: (1) the negative control group without lipopolysaccharide (LPS, control), (2) the positive control group with LPS infusion (LPS group), (3) the albumin-treated LPS group (ALB+LPS group), and (4) the BT086-treated LPS group (BT086 + LPS group). A standardized amount of E. coli was intravenously injected into all of the animals. The vital parameters, the concentration of E. coli in the blood and other organs, the residual granulocyte phagocytosis activity, and the levels of the inflammatory mediators were measured. Histological changes in the lung and liver tissue were examined following autopsy. RESULTS: The elimination of E. coli from the bloodstream was expedited in the BT086-treated group compared with the LPS- and albumin-treated groups. The BT086 + LPS group exhibited higher phagocytic activity of polymorphonuclear neutrophils (PMNs) than the control and ALB+LPS groups. The liver energy stores were higher in the BT086 + LPS group than in the other groups. CONCLUSION: Our data suggest that the IgM-enriched IVIG has the potential to improve host defense in a rabbit model of endotoxemia. Studies using different animal models and dosages are necessary to further explore the potential benefits of IgM-enriched IVIG solutions.