Eco-friendly synchronous fluorescence spectrofluorimetric method for simultaneous determination of montelukast sodium and fexofenadine hydrochloride in their antiallergic rhinitis fixed-dose combination tablets.

An innovative, simple, accurate, sensitive, and eco-friendly synchronous fluorescence spectrofluorimetric method has been developed for the simultaneous analysis of montelukast sodium (MON) and fexofenadine hydrochloride (FEX). The method relies on measuring the relative synchronous fluorescence intensity of both drugs using Δλ of 60 nm in methanol at 405 nm for MON and 288 nm for FEX. The experimental parameters influencing the developed method were investigated and optimized. The method was linear over the ranges 0.1-2.0 and 2.0-20.0 µg/ml for MON and FEX, respectively. The limits of detection were 0.018 and 0.441 µg/ml, and the limits of quantitation were 0.055 and 1.336 µg/ml for MON and FEX, respectively. The developed method was applied successfully for the determination of the two drugs in their newly released fixed-dose combination prescribed for the treatment of allergic rhinitis. The mean per cent recoveries were found to be 100.680 ± 0.890 and 100.110 ± 0.940 for MON and FEX, respectively. Furthermore, the method was found to be eco-friendly green as was evaluated according to the Green Analytical Procedure Index tool guidelines and analytical eco-scale.

A fast and green reversed-phase HPLC method with fluorescence detection for simultaneous determination of amlodipine and celecoxib in their newly approved fixed-dose combination tablets.

A fast, green, sensitive, and accurate analytical method using high-performance liquid chromatography couple with fluorescence detection was established and validated for the simultaneous determination of amlodipine besylate and celecoxib in their recently approved fixed-dose combination tablets (1:20). Separation of the two drugs was achieved on C18 reversed-phase column (Thermo ODS Hypersil, 4.6 × 250 mm, particle size 5 µm) using acetonitrile:potassium phosphate buffer (50 mM; pH 5.5, 60:40 v/v) as a mobile phase at 40°C, which eluted at a rate of 1 mL/min. Detection was carried out with excitation and emission wavelengths of 360 and 446 nm for amlodipine and 265 and 359 nm for celecoxib, respectively. The method was linear over a concentration range of 0.05-2 and 0.05-10 µg/mL and limit of detection reached to 0.017 and 0.0167 µg/mL for amlodipine and celecoxib, respectively. The developed method was successfully applied to assess the cited drugs in their newly FDA approved fixed-dose combination tablet dosage form. Furthermore, the method was found to be sensitive and eco-friendly green alternative to the reported methods as it was evaluated according to the green analytical procedure index tool guidelines and analytical Eco-Scale.

A Case of Disseminated Lyme Disease Presenting as Chronic Urticaria.

We present a case of cyclical bouts of chronic urticaria on the abdomen, scalp, and hands in a patient with disseminated Lyme disease. Lyme disease traditionally presents as a cutaneous lesion known as erythema migrans, which alerts patients and physicians that diagnosis and treatment is necessary. This case highlights the importance of variable cutaneous presentations of Lyme disease, especially if nerve pain is concurrent.

Efficacy of Combined Intense Pulsed Light (IPL) With Fractional CO2 -Laser Ablation in the Treatment of Large Hypertrophic Scars: A Prospective, Randomized Control Trial.

BACKGROUND AND OBJECTIVES: Scar rehabilitation is a complex process that incorporates medical, surgical, and physical therapeutic measures to best restore function and visual normalcy. Lasers have emerged as essential tools in the management of scars, with devices available to address scar size, dyschromia, and contour irregularities. As different lasers treat these different features, multi-laser, same session therapeutic approaches may offer a more comprehensive approach to scar revision. In this study, we aim to demonstrate the effect of a combinatorial, same session treatment with intense pulsed light (IPL) and fractional ablative CO2 as compared to single laser treatment with fractional ablative CO2 laser alone or control in the treatment of mature hypertrophic scars. MATERIALS AND METHODS: This institutional review board-approved, randomized controlled trial, enrolled 23 healthy adults with large (>100 cm2 ) hypertrophic scars who were randomized to one of three treatment arms: (i) IPL and CO2 ablative fractional laser (AFL), (ii) CO2 AFL alone, and (iii) control (no laser treatment). Subjects underwent a total of four treatment sessions at 6-8-week intervals with follow-up visits at 1, 3, and 6 months following the last treatment session. Primary endpoints included blinded scoring of before and after photographs via the Manchester Scar Scale (MSS). Secondary endpoints included the Patient-Observer Scar Assessment Scale (POSAS). RESULTS: As compared to control and CO2 AFL laser alone, the combination of CO2 AFL and IPL demonstrated statistically significant improvement across a greater number of scar domains, as assessed by the MSS. 100% of subjects in both treatment groups showed a statistically significant decrease in the POSAS scale after the series of four treatment sessions. No adverse events were reported. CONCLUSION: Treatment with combined IPL and CO2 AFL demonstrated higher average improvements across the majority of assessed scar domains, as compared to both control and CO2 laser alone. The difference was not statistically significant in overall MSS score as expected due to the role of CO2 as the main source of improvement. However, only the combination group had statistically significant improvement in both color and texture. These findings support the assertion that a multi-photo-thermolytic approach with combined IPL and CO2 AFL can have a positive impact on the treatment of hypertrophic scars by using multiple wavelengths to maximize laser-skin interactions in targeting the different chromophores expressed in scar tissue. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Anti-N and anti-Doa immunoglobulin G alloantibody-mediated delayed hemolytic transfusion reaction with hyperhemolysis in sickle cell disease treated with eculizumab and HBOC-201: case report and review of the literature.

BACKGROUND: Delayed hemolytic transfusion reaction (DHTR) with hyperhemolysis is a potentially fatal complication resulting from alloimmunization that can cause severe hemolysis of both transfused and intrinsic red blood cells (RBCs). Patients with sickle cell disease often receive multiple RBC units during their lifetime and thus are likely to develop alloantibodies that increase the risk for DHTR. Treatment to decrease hemolysis includes intravenous immunoglobulin (IVIG), steroids, eculizumab, rituximab, and plasmapheresis in addition to erythropoietin (EPO), intravenous (IV) iron, vitamin B12, and folate to support erythropoiesis. RBC transfusion is preferably avoided in DHTR due to an increased risk of exacerbating the hemolysis. CASE REPORT: We report a rare case of anti-N and anti-Doa immunoglobulin (Ig)G alloantibody-mediated life-threatening DHTR with hyperhemolysis in a patient with hemoglobin SS after RBC transfusion for acute chest syndrome who was successfully treated with eculizumab and HBOC-201 (Hemopure) in addition to steroids, IVIG, EPO, IV iron, and vitamin B12. HBOC-201 (Hemopure) was successfully used as a RBC alternative in this patient. CONCLUSION: Anti-N and anti-Doa IgG alloantibodies can rarely cause severe life-threatening DHTR with hyperhemolysis. HBOC-201 (Hemopure) can be a lifesaving alternative in this scenario. Our report also supports the use of eculizumab in DHTR; however, prospective studies are needed to determine the appropriate dose and sequence of eculizumab administration.

Application of Incident Command Structure to clinical trial management in the academic setting: principles and lessons learned.

BACKGROUND: Clinical trial success depends on appropriate management, but practical guidance to trial organisation and planning is lacking. The Incident Command System (ICS) is the 'gold standard' management system developed for managing diverse operations in major incident and public health arenas. It enables effective and flexible management through integration of personnel, procedures, resources, and communications within a common hierarchical organisational structure. Conventional ICS organisation consists of five function modules: Command, Planning, Operations, Logistics, and Finance/Administration. Large clinical trials will require a separate Regulatory Administrative arm, and an Information arm, consisting of dedicated data management and information technology staff. We applied ICS principles to organisation and management of the Prehospital Use of Plasma in Traumatic Haemorrhage (PUPTH) trial. This trial was a multidepartmental, multiagency, randomised clinical trial investigating prehospital administration of thawed plasma on mortality and coagulation response in severely injured trauma patients. We describe the ICS system as it would apply to large clinical trials in general, and the benefits, barriers, and lessons learned in utilising ICS principles to reorganise and coordinate the PUPTH trial. RESULTS: Without a formal trial management structure, early stages of the trial were characterised by inertia and organisational confusion. Implementing ICS improved organisation, coordination, and communication between multiple agencies and service groups, and greatly streamlined regulatory compliance administration. However, unfamiliarity of clinicians with ICS culture, conflicting resource allocation priorities, and communication bottlenecks were significant barriers. CONCLUSIONS: ICS is a flexible and powerful organisational tool for managing large complex clinical trials. However, for successful implementation the cultural, psychological, and social environment of trial participants must be accounted for, and personnel need to be educated in the basics of ICS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02303964 . Registered on 28 November 2014.

Prehospital use of plasma in traumatic hemorrhage (The PUPTH Trial): study protocol for a randomised controlled trial.

BACKGROUND: Severe traumatic injury and haemorrhagic shock are frequently associated with disruptions of coagulation function (such as trauma-induced coagulopathy TIC) and activation of inflammatory cascades. These pathologies may be exacerbated by current standard of care resuscitation protocols. Observational studies suggest early administration of plasma to severely-injured haemorrhaging patients may correct TIC, minimise inflammation, and improve survival. The proposed randomised clinical trial will evaluate the clinical effectiveness of pre-hospital plasma administration compared with standard- of-care crystalloid resuscitation in severely-injured patients with major traumatic haemorrhage. METHODS/DESIGN: This is a prospective, randomized, open-label, non-blinded trial to determine the effect of pre-hospital administration of thawed plasma (TP) on mortality, morbidity, transfusion requirements, coagulation, and inflammatory response in severely-injured bleeding trauma patients. Two hundred and ten eligible adult trauma patients will be randomised to receive either two units of plasma, to be administered in-field, vs standard of care normal saline (NS). Main analyses will compare subjects allocated to TP to those allocated to NS, on an intention-to-treat basis. Primary outcome measure is all-cause 30-day mortality. Secondary outcome measures include coagulation and lipidomic/pro-inflammatory marker responses, volume of resuscitation fluids (crystalloid, colloid) and blood products administered, and major hospital outcomes (e.g. incidence of MSOF, length of ICU stay, length of hospital stay). DISCUSSION: This study is part of a US Department of Defense (DoD)-funded multi-institutional investigation, conducted independently of, but in parallel with, the University of Pittsburgh and University of Denver. Demonstration of significant reductions in mortality and coagulopathic/inflammatory-related morbidities as a result of pre-hospital plasma administration would be of considerable clinical importance for the management of haemorrhagic shock in both civilian and military populations. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02303964 on 28 November 2014.

Responses on a lateralized lexical decision task relate to both reading times and comprehension.

Research over the last few years has shown that the dominance of the left hemisphere in language processing is less complete than previously thought [Beeman, M. (1993). Semantic processing in the right hemisphere may contribute to drawing inferences from discourse. Brain and Language, 44, 80-120; Faust, M., & Chiarello, C. (1998). Sentence context and lexical ambiguity resolution by the two hemispheres. Neuropsychologia, 36(9), 827-835; Weems, S. A., & Zaidel, E. (2004). The relationship between reading ability and lateralized lexical decision. Brain and Cognition, 55(3), 507-515]. Engaging the right brain in language processing is required for processing speaker/writer intention, particularly in those subtle interpretive processes that help in deciphering humor, irony, and emotional inference. In two experiments employing a divided field or lateralized lexical decision task (LLDT), accuracy and reaction times (RTs) were related to reading times and comprehension on sentence reading. Differences seen in RTs and error rates by visual fields were found to relate to performance. Smaller differences in performance between fields tended to be related to better performance on the LLDT in both experiments and, in Experiment 1, to reading measures. Readers who can exploit both hemispheres for language processing equally appear to be at an advantage in lexical access and possibly also in reading performance.

The Pittsburgh Agitation Scale: A User-Friendly Instrument for Rating Agitation in Dementia Patients.

There are many rating instruments designed to assess symptoms of agitation in patients with dementia. Most scales require that raters assess multiple specific behaviors over several days, limiting the use of such scales to clinical staff who have direct contact with patients but do not have the time to complete a comprehensive assessment following each period of observation. Also, scales that assess behavior over several days must rely on "secondhand" information describing behaviors not directly observed by the rater. The Pittsburgh Agitation Scale (PAS) is an easy-to-use instrument, based on direct observations of the patient, that was developed to monitor the severity of agitation associated with dementia. Interrater reliability and measures of validity have been established with clinical staff on a busy psychogeriatric inpatient unit and with research personnel in a nursing home setting.