Screening and detection of delirium in older ED patients: performance of the modified Confusion Assessment Method for the Emergency Department (mCAM-ED). A two-step tool

Delirium is frequent in older Emergency Department (ED) patients, but detection rates for delirium in the ED are low. To aid in identifying delirium, we developed and implemented a two-step systematic delirium screening and assessment tool in our ED: the modified Confusion Assessment Method for the Emergency Department (mCAM-ED). Components of the mCAM-ED include: (1) screening for inattention, the main feature of delirium, which was performed with the Months Backwards Test (MBT); (2) delirium assessment based on a structured interview with questions from the Mental Status Questionnaire by Kahn et al. and the Comprehension Test by Hart et al. The aims of our study are (1) to investigate the performance criteria of the mCAM-ED tool in a consecutive sample of older ED patients, (2) to evaluate the performance of the mCAM-ED in patients with and without dementia and (3) to test whether this tool is efficient in keeping evaluation time to a minimum and reducing screening and assessment burden on the patient. For this prospective validation study, we recruited a consecutive sample of ED patients aged 65 and older during an 11-day period in November 2015. Trained nurses assessed patients with the mCAM-ED. Results were compared to the reference standard [i.e. the geriatricians’ delirium diagnosis based on the criteria of the Text Revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR)]. Performance criteria were computed. We included 286 consecutive ED patients aged 65 and older. The median age was 80.02 (Q₁ = 72.15; Q₃ = 86.76), 58.7% of included patients were female, 14.3% had dementia. We found a delirium prevalence of 7.0%. In patients with dementia, specificity and positive likelihood ratio were lower. When compared to the reference standard, delirium assessment with the mCAM-ED has a 0.98 specificity and a 39.9 positive likelihood ratio. In 80.0% of all cases, the first step of the mCAM-ED, i.e. screening for inattention with the MBT, took less than 30 s. On average, the complete mCAM-ED assessment required 3.2 (SD 2.0), 5.6 (SD 3.2), and 6.2 (SD 2.3) minutes in cognitively unimpaired patients, patients with dementia and patients with dementia or delirium, respectively. The mCAM-ED is able to efficiently rule out delirium as well as confirm the diagnosis of delirium in elderly patients with and without dementia and applies minimal screening and assessment burden on the patient.     

Ungew?hnliche Hautver?nderungen bei 72-j?hriger Patientin mit multiplem Myelom

We report on a 72-year-old female patient with multiple myeloma who presented with alopecia and eye-catching alterations of the skin and the nails. A biopsy of the skin could confirm the diagnosis of immunoglobulin light chain (AL) amyloidosis, which was also suspected of having affected other organs. After six cycles of a cytoreductive therapy with bortezomib and dexamethasone a very good partial response of the multiple myeloma was seen and an improvement in the skin and nail alterations could be achieved.     

Innovative trial designs are practical solutions for improving the treatment of tuberculosis

A growing number of new drugs for the treatment of tuberculosis are in clinical development. Confirmatory phase 3 trials are expensive and time-consuming and the question of whether one particular drug combination can be used to treat tuberculosis is less important from a public health perspective than the question of which are the shortest, simplest, most effective, and safest regimens. While preclinical and phase 1 studies provide some guidance in the selection of combinations for clinical evaluation, a large number of combinations will require phase 2 testing to ensure that only the best regimens advance to phase 3. The multi-arm multi-stage trial design is an example of a treatment selection-adaptive design where multiple experimental arms are each simultaneously compared with a common control and interim analyses allow for poor performing arms to be dropped early. Such designs, if designed and implemented correctly, require fewer patients, can be completed in a shorter time frame, and answer more relevant questions without any loss in statistical validity or scientific integrity. There are, however, practical issues that must be considered in applying this in tuberculosis treatment trials. More innovative trials designs should be considered to speed drug and regimen development for the treatment of tuberculosis.     

Platelet Inhibition by Abciximab Bolus-Only Administration and Oral ADP Receptor Antagonist Loading in Acute Coronary Syndrome Patients: The Blocking and Bridging Strategy

Introduction

Current guidelines still recommend the bolus and infusion administration of glycoprotein IIbIIIa inhibitors in patients with high-risk acute coronary syndrome undergoing percutaneous coronary intervention. We sought to evaluate the extent of platelet inhibition by a blocking and bridging strategy with intracoronary abciximab bolus-only administration and oral loading of adenosine diphosphate receptor antagonists.

Patients and methods

Fifty-six consecutive high-risk acute coronary syndrome patients with bolus-only abciximab administration (0.25 mg/kg i.c.) and loading with 600 mg clopidogrel (55%) or 60 mg prasugrel (45%) were included in this study. Platelet aggregation induced by thrombin receptor-activating peptide and adenosine diphosphate was measured by multiple electrode aggregometry up to 7 days.

Results

Thrombin receptor-activating peptide induced platelet aggregation was significantly suppressed for a minimum of 48 h (45 ± 17 U) and returned to a normal range (> 84 U) after 6 days (90 ± 26 U; p < 0.001). Co-medication with prasugrel significantly reduced adenosine diphosphate-induced (p = 0.002) and thrombin receptor-activating peptide-induced (p = 0.02) platelet aggregation compared with clopidogrel throughout the observation period. No stent thrombosis or repeat myocardial infarction occurred at 30-day follow-up.

Conclusions

Immediate blocking of platelet aggregation in high-risk acute coronary syndrome patients by intracoronary abciximab bolus-only administration and bridging to prolonged inhibition via oral blockade of ADP receptors effectively inhibited overall platelet reactivity for at least 48 h, questioning the value of continuous abciximab infusion. Co-medication with prasugrel vs. clopidogrel synergistically augmented platelet inhibition.     

Quantitative MRI and loss of free ambulation in Duchenne muscular dystrophy

The purpose of this ethics approved trial was to correlate quantitative MRI with functional abilities in both ambulant and non-ambulant Duchenne muscular dystrophy (DMD). Twenty patients with genetically confirmed DMD were recruited. Physical assessment was performed using the motor function measurement (MFM) scale. Axial 3T MRI scans of the thighs were acquired using T1-weighted in- and opposed-phase images (TR = 20 ms, TE₁ = 2.45 ms, TE₂ = 3.68 ms, flip angle = 15°) to calculate the relative fat fraction according to the two-point Dixon method in the knee extensors, flexors, and adductor muscles. The average MFM was 65.3 % and correlated negatively to age (r ² = 0.60). Overall mean fat fraction correlated positively to age (r ² = 0.51–0.64). An average of 5 % increase in mean fat fraction per year was calculated. Mean fat fraction of the quadriceps showed a high negative correlation (r ² = 0.93) to the D1 (standing position and transfers) component of the MFM. A cutoff for mean fat fraction of 50 % predicted loss of ambulation with a sensitivity of 100 % and a specificity of 91 %. Therefore, quantitative muscle MRI seems to be a promising endpoint for short clinical trials evaluating the effect of newer treatments on the time of loss of ambulation in DMD.     

D-Optimal Design in the Development of Rheologically Improved In Situ Forming Ophthalmic Gel

In situ forming ophthalmic gels need to be fine tuned considering all the biopharmaceutical challenges of the front of the eye in order to increase drug residence time at the application site resulting in its improved bioavailability and efficacy. The aim of this study was to develop in situ forming ophthalmic poloxamer P407/poloxamer P188/chitosan gel fine tuned in terms of polymer content, temperature of gelation, and viscosity. Minimizing the total polymer content while retaining the advantageous rheological properties has been achieved by means of D-optimal statistical design. The optimal in situ forming gel was selected based on minimal polymer content (P407, P188, and chitosan concentration of 14.2%, 1.7%, and 0.25% w/w, respectively), favorable rheological characteristics, and in vitro resistance to tear dilution. The optimal in situ forming gel was proved to be robust against entrapment of active pharmaceutical ingredients making it a suitable platform for ophthalmic delivery of active pharmaceutical ingredients with diverse physicochemical properties.     

In utero bisphenol A exposure disrupts germ cell nest breakdown and reduces fertility with age in the mouse

Bisphenol A (BPA) is a known reproductive toxicant in rodents. However, the effects of in utero BPA exposure on early ovarian development and the consequences of such exposure on female reproduction in later reproductive life are unclear. Thus, we determined the effects of in utero BPA exposure during a critical developmental window on germ cell nest breakdown, a process required for establishment of the finite primordial follicle pool, and on female reproduction. Pregnant FVB mice (F0) were orally dosed daily with tocopherol-striped corn oil (vehicle), diethylstilbestrol (DES; 0.05 μg/kg, positive control), or BPA (0.5, 20, and 50 μg/kg) from gestational day 11 until birth. Ovarian morphology and gene expression profiles then were examined in F1 female offspring on postnatal day (PND) 4 and estrous cyclicity was examined daily after weaning for 30 days. F1 females were also subjected to breeding studies with untreated males at three to nine months. The results indicate that BPA inhibits germ cell nest breakdown via altering expression of selected apoptotic factors. BPA also significantly advances the age of first estrus, shortens the time that the females remain in estrus, and increases the time that the females remain in metestrus and diestrus compared to controls. Further, F1 females exposed to low doses of BPA exhibit various fertility problems and have a significantly higher percentage of dead pups compared to controls. These results indicate that in utero exposure to low doses of BPA during a critical ovarian developmental window interferes with early ovarian development and reduces fertility with age.