Search

Objective: To investigate whether caloric vestibular stimulation, a non-invasive form of neuromodulation, alters the level of awareness in people residing in a minimally conscious state. Design: Single-case (n = 2), prospective, controlled (ABAB) efficacy study. Setting: Tertiary, neuro-rehabilitation inpatient ward within a university hospital. Participants: Two individuals in a minimally conscious state. Intervention: Left ear caloric vestibular stimulation was performed in two four/five-week blocks interleaved with two four/five-week blocks of sham stimulation. Session duration and frequency gradually increased within each block from once per day for 10 minutes (Week 1) to once per day for 20 minutes (Week 2) to 20 minutes twice per day in the remaining weeks. Measures: Wessex Head Injury Matrix, JFK Coma Recovery Scale - Revised. Results: Both participants' Wessex Head Injury Matrix scores indicated a transition from involuntary (i.e. mechanical vocalization) to voluntary (i.e. gesture making, selective responses to family members) behaviour that was time-locked to the onset of active stimulation. In one participant, this improvement persisted for at least four weeks after active stimulation, while in the other it diminished two weeks after stimulation. Allied, although less dramatic, changes were seen on the arousal and auditory subscales of the JFK Coma Recovery Scale - Revised. Conclusion: The data provide the first evidence that vestibular stimulation may help improve outcome in a low awareness state, although further studies are needed to replicate effect and determine longer-term benefit. [ABSTRACT FROM AUTHOR]

Purpose: Hypertrophic pyloric stenosis (HPS) is a common condition of infancy, often presenting with marked biochemical derangement, requiring correction. Previous studies have looked at the relationship between serum electrolytes and acid-base balance in HPS but not at the relationship between the degree of biochemical derangement and time taken to resolve the biochemical abnormality.Methods: Retrospective analysis was performed on all 151 infants undergoing pyloromyotomy over a 3 year period. Of these, 105 met the inclusion criteria of: compliance with the unit HPS fluid protocol, and the documentation of at least three serial biochemical investigations. The rate of correction for each biochemical marker (sodium, potassium, chloride, urea, pCO2, hydrogen ion concentration, bicarbonate and the base excess) was plotted against the degree of disturbance and then against time.Results: A significant relationship (P < 0.01) was found between the rate of correction of an abnormal chloride, urea or base excess and the degree of initial derangement. This enables the prediction of the time taken for the required correction of biochemical abnormalities prior to theatre.Conclusion: This method of analysis may be of value in comparing the effectiveness of different fluid regimes in use for the correction of biochemical abnormalities in infants with IHPS. [ABSTRACT FROM AUTHOR]

Purpose: Haemolytic uraemic syndrome (HUS) is the commonest childhood cause of acute renal failure. Peritoneal dialysis peritonitis (PDP) is a well-recognised complication, with some children requiring surgical intervention (SI). The aim of this study is to determine whether the presence of enteric organisms in cases of PDP might predict the need for SI.Methods: Retrospective, 5-year (2009-2014) case note review of all HUS cases requiring PD presenting to a single centre. Mann-Whitney U test was used for continuous non-parametric data and χ (2) for categorical data.Results: 48 children required PD for HUS, 18/48 (38 %) developed PDP and of these 5/18 (28 %) required SI (subtotal colectomy n = 4, small bowel resection n = 1). Peritoneal fluid was cultured as part of the work-up for PDP. The presence of enteric organisms was associated with a 10.4 fold relative risk of requiring surgery (p = 0.02, 95 % CI 1.5-71.9), with 4/5 of these patients requiring surgery (median 17 days post-culture result). Only 1/13 patients not requiring surgery grew gram-negative bacteria.Conclusion: The presence of enteric bacteria in patients with PDP significantly decreases the chances of successful conservative management. In these patients early involvement of the surgical team is essential with a low threshold for SI. [ABSTRACT FROM AUTHOR]

Background: In human beings, 5-HT6 receptors are almost exclusively expressed in the brain, particularly in areas relevant for cognition, such as the hippocampus and frontal cortex. We assessed the effect on cognitive performance of Lu AE58054 (idalopirdine), a selective 5-HT6 receptor antagonist, in donepezil-treated patients with moderate Alzheimer's disease.Methods: For this randomised, double-blind, placebo-controlled phase 2 trial (LADDER), we recruited patients from 48 outpatient clinical sites in seven countries. Patients were 50 years or older, had moderate Alzheimer's disease (a mini-mental state examination score of 12-19), and had been stably treated with donepezil 10 mg per day for 3 or more months. Using a computer-generated sequence, we randomly assigned patients (1:1, stratified by site) to receive either idalopirdine 90 mg per day (30 mg thrice daily) or placebo. The primary endpoint was change from baseline in the 11-item Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) at week 24. We analysed all efficacy endpoints in the full-analysis set (modified intention-to-treat analysis). This trial is registered with ClinicalTrials.gov, number NCT01019421.Findings: Between Dec 8, 2009, and Dec 23, 2011, we randomly allocated 278 patients to treatment: 133 to placebo and 145 to idalopirdine. 132 patients in the placebo group and 140 in the experimental group were included in the final analysis. At week 24, the change from baseline in ADAS-cog total score was +1·38 (SD 0·53) in the placebo group and -0·77 (0·55) in the idalopirdine group (treatment difference of -2·16 points, 95% CI -3·62 to -0·69; p=0·0040). 25 patients (seven taking placebo and 18 taking idalopirdine) discontinued treatment because of adverse events, the difference between groups being mainly due to asymptomatic transient increases in transaminase concentrations in some idalopirdine-treated patients. The most common adverse events (occurring in >3% of patients) were increased γ-glutamyltransferase (14 [10%] patients in the idalopirdine group vs two [2%] in the placebo group), diarrhoea (six [4%] vs nine [7%]), urinary tract infection (three [2%] vs nine [7%]), fall (three [2%] vs eight [6%]), increased alanine aminotransferase (nine [6%] vs none), and benign prostatic hyperplasia (two [5%] vs none). Serious adverse events were reported by 14 (10%) patients in the idalopirdine group and 13 (10%) patients in the placebo group. One death occurred in each treatment group, neither were regarded as being related to treatment.Interpretation: Idalopirdine improved cognitive function in donepezil-treated patients with moderate Alzheimer's disease. Larger studies in a broader population of patients are ongoing to substantiate the effects reported here.Funding: H Lundbeck A/S. [ABSTRACT FROM AUTHOR]

Background/Aims: We aimed to develop realistic definitions of clinical worsening in advanced Alzheimer's disease (AD) and to use them in a post hoc responder analysis of memantine. Methods: 2,340 patients with moderate to severe AD (Mini-Mental State Examination <20) were included from 9 multicentre, 16- to 28-week, randomised, double-blind, placebo-controlled studies of memantine 20 mg/day versus placebo. Responder meta-analyses were performed, with definitions of response based on minimally important differences (MIDs) on cognitive, functional, and global assessment scales. Validated or established MIDs were used where available; otherwise, MIDs were estimated by a data-driven approach, using data from our moderate to severe AD population. Results: Patients with moderate to severe AD treated with memantine had a lower incidence of worsening from baseline to endpoint than patients treated with placebo, in cognition [24.4 vs. 35.0%; odds ratio (OR) = 0.60; p < 0.001], function (38.1 vs. 43.4%; OR = 0.81; p = 0.01), global status (39.8 vs. 48.6%; OR = 0.70; p < 0.001), and in a combined 'triple' worsening measure (9.4 vs. 16.1%; OR = 0.54; p < 0.001). Conclusions: New definitions of clinical worsening based on MIDs represent a more realistic functional decline in advanced stages of AD. Results of this new analysis show that memantine reduces the incidence of clinical worsening in key symptomatic domains in moderate to severe AD. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

To better characterize response to donepezil in patients with severe AD, Severe Impairment Battery (SIB) data were pooled from four donepezil clinical trials (N=904). Changes in SIB total and domain scores from baseline to week 24 were compared between placebo and donepezil treatment groups (observed case analysis). Analyses were stratified by baseline severity (Mini-Mental State Examination [MMSE] scores 1-5, 6-9, 10-12 and 13-17) to allow investigation of responses at different stages of cognitive impairment. Relationships to global and functional measures were explored. The difference between donepezil- and placebo-treated patients in least squares (LS) mean change in SIB total scores from baseline to week 24 was 6.22 (p < 0.0001, Cohen's d, 0.53). Treatment-placebo differences were statistically significant for each baseline severity stratum, being greatest for the MMSE 6-9 stratum (LS mean difference, 7.60; p < 0.0001, Cohen's d, 0.66). Treatment-placebo differences in LS mean change in SIB domain scores significantly favored donepezil for seven of nine domains (range, p = 0.0056 to p < 0.0001; Cohen's d, 0.17-0.48). Change in total SIB score correlated significantly with change in measures of activities of daily living and global status. These results indicate that donepezil provides cognitive benefits in patients with severe AD, including those most markedly impaired. The treatment effect size and correlation between improvements in SIB scores and functional and global outcome measures suggest the drug-placebo differences are clinically meaningful. [ABSTRACT FROM AUTHOR]

Objective To determine the long-term tolerability and efficacy of donepezil in patients with vascular dementia (VaD). Methods International, multicentre, open-label, 30-week extension study of two 24-week, randomised, double-blind, placebo-controlled studies. Participants were ambulatory adults (59% female; mean age, 74.7 ± 0.3) with a diagnosis of possible or probable VaD and without a diagnosis of Alzheimer's disease, who were medically stable and had completed one of two double-blind studies. All patients received donepezil 5 mg/day for the first 6 weeks, then 10 mg/day (clinician approval required). Assessments were performed at week 6 and every 12 weeks thereafter. The main outcome measure was the Alzheimer's disease Assessment Scale-cognitive subscale (ADAS-cog). Safety/tolerability measures included adverse events (AEs) and physical and laboratory evaluations. Results Of 1219 eligible patients, 885 (72.6%) were enrolled, of which 707 (79.9%) completed the study; 127 (14.4%) patients discontinued due to AEs. A mean reduction (0.6–1.15 points) from double-blind study baseline score to week 54 (end of open-label study) on the ADAS-cog was observed for patients who received donepezil continuously for 54 weeks. ADAS-cog scores remained stable in the group that initiated donepezil treatment during the extension study. Most common donepezil-related AEs were nausea (occurring in 5.3%) and diarrhoea (8.8%); no unexpected AEs attributable to donepezil occurred. Conclusion These data suggest that donepezil improves cognition for up to 54 weeks in patients with VaD. Patients initiating donepezil in this extension study did not perform as well on the primary outcome measure as those initiating donepezil in the double-blind study. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Congenital diaphragmatic hernia (CDH) is associated with high mortality due to lung hypoplasia, pulmonary hypertension and co-existent anomalies. This paper highlights recent progress in the perinatal management of CDH and addresses long term outcome issues for survivors indicating the need for multidisciplinary follow up. [Copyright &y& Elsevier]

Background: Therapeutic endpoints based on reduced clinical worsening represent clinically relevant and realistic goals for patients suffering from progressive neurodegenerative disorders such as Alzheimer’s disease (AD). Methods: Data from 906 patients (388 receiving placebo; 518 receiving donepezil) with mild-to-moderate AD [Mini-Mental State Examination (MMSE) score 10–27] were pooled from 3 randomized, double-blind placebo-controlled studies. Clinical worsening was defined as decline in (1) cognition (MMSE), (2) cognition and global ratings (Clinician’s Interview-Based Impression of Change plus Caregiver Input/Gottfries-Bråne-Steen scale) or (3) cognition, global ratings and function (various functional measures). Results: At week 24, lower percentages of donepezil-treated patients than placebo patients met the criteria for clinical worsening, regardless of the definition. The odds of declining were significantly reduced for donepezil-treated versus placebo patients (p < 0.0001; all definitions). Among patients meeting criteria for clinical worsening, mean declines in MMSE scores were greater for placebo than donepezil-treated patients. Conclusion: In this population, donepezil treatment was associated with reduced odds of clinical worsening of AD symptoms. Moreover, patients worsening on donepezil were likely to experience less cognitive decline than expected if left untreated. This suggests that AD patients showing clinical worsening on donepezil may still derive benefits compared with placebo/untreated patients. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article discusses the efficacy of 5-fluorouracil (5-FU) treatment for patients with actinic keratosis (AK) lesions. AK lesions are characterized with dry, rough, yellow-brown, scaly plaques. It notes that AKs are typically caused by chronic exposure to ultraviolet (UV) radiation among fair-skinned individuals. The treatment for AKs can be possible using the 5-FU, an antineoplastic antimetabolite, which interferes with the synthesis of DNA and RNA provoking unbalanced cell growth and death.

Abstract: Alzheimer''s disease (AD) is a growing problem in an ageing population. Specific symptomatic treatments are now available for use in AD. The cholinesterase inhibitors (ChEIs) donepezil, galantamine and rivastigmine improve cholinergic function providing modest but clinically relevant improvements in cognition, activities of daily living, behaviour and consequently a reduction in caregiver burden. AD is a degenerative disorder and symptomatic treatments do not stop the underlying disease process. Nevertheless, despite an overall decline in cognitive scores over time, patients still maintain an advantage over untreated patients, demonstrated for donepezil in placebo-controlled studies of 1 year''s duration. Continued treatment may help to delay the need for 24-hour care. The ChEIs have broadly similar efficacy despite some differences in modes of action and side-effects. Memantine is an NMDA receptor antagonists licensed for the treatment of moderate to severe AD, although, as with the ChEIs, there are studies demonstrating benefits in the whole spectrum of the disease. Memantine is well tolerated and although the original pivotal study in moderately severe AD showed benefits in terms of slowing of decline, improvements have been seen when used in conjunction with donepezil and in mild-to-moderate AD studies. The additional benefit demonstrated by addressing both the glutamatergic and cholinergic dysfunction may herald more combined approaches to treating this complex disease. Other avenues, such as antioxidants, oestrogens and anti-inflammatory drugs, have not shown any convincing benefits. The use of statins has shown some early positive results and a definitive trial is in progress. [Copyright &y& Elsevier]

Hypothesis Necrotizing soft tissue infection (NSTI) refers to a spectrum of infective diseases characterized by necrosis of the deep soft tissues. Features of manifestation and medical management have been analyzed for association with outcome. The use of hyperbaric oxygen (HBO2) therapy has been recommended as an adjunctive treatment but remains controversial. Design Retrospective cohort study. Setting A major tertiary hospital. Patients All patients admitted with a diagnosis of NSTI across a 5-year period. Intervention Features of manifestation and medical management were analyzed for their association with survival to hospital discharge. Long-term survival was analyzed for the intervention of HBO2 therapy. Main Outcome Measures Primary outcome was survival to hospital discharge. Secondary outcomes were limb salvage and long-term survival after hospital discharge. Results Forty-four patients were reviewed, with 6 deaths (14%). Survival was less likely in those with increased age, renal dysfunction, and idiopathic etiology of infection and in those not receiving HBO2 therapy. Logistic regression determined the strongest association with survival was the intervention of HBO2 therapy (P = .02). Hyperbaric oxygen therapy increased survival with an odds ratio of 8.9 (95% confidence interval, 1.3-58.0) and a number needed to treat of 3. For NSTI involving an extremity, HBO2 therapy significantly reduced the incidence of amputation (P = .05). Survival analysis revealed an improved long-term outcome for the HBO2 group (P = .002). Conclusion Hyperbaric oxygen therapy was associated with improved survival and limb salvage and should be considered in the setting of NSTI. [ABSTRACT FROM AUTHOR]

The deficiency in cholinergic neurotransmission in Alzheimer's disease has led to the development of cholinesterase inhibitors as the first-line treatment for symptoms of this disease. The clinical benefits of these agents include improvements, stabilisation or less than expected decline in cognition, function and behaviour. The common mechanism of action underlying this class of agents is an increase in available acetylcholine through inhibition of the catabolic enzyme, acetylcholinesterase. There is substantial evidence that the cholinesterase inhibitors, including donepezil, galantamine and rivastigmine, decrease acetylcholines- terase activity in a number of brain regions in patients with Alzheimer's disease. There is also a significant correlation between acetylcholinesterase inhibition and observed cognitive improvement. However, the cholinesterase inhibitors are reported to have additional pharmacological actions. Rivastigmine inhibits butyrylcholinesterase with a similar affinity to acetylcholinesterase, although it is not clear whether the inhibition of butyrylcholinesterase contributes to the therapeutic effect of rivastigmine. Based on data from preclinical studies, it has been proposed that galantamine also potentiates the action of acetylcholine on nicotinic receptors via allosteric modulation; however, the effects appear to be highly dependent on the concentrations of agonist and galantamine. It is not yet clear whether these concentrations are related to those achieved in the brain of patients with Alzheimer's disease within therapeutic dose ranges. Preclinical studies have shown that donepezil and galantamine also significantly increase nicotinic receptor density, and increased receptor density may be associated with enhanced synaptic strengthening through long-term potentiation, which is related to cognitive function. Despite these differences in pharmacology, a review of clinical data, including head-to-head studies, has not demonstrated differences in efficacy, although they may have an impact on tolerability. It seems clear that whatever the subsidiary modes of action, clinical evidence supporting acetylcholinesterase inhibition as the mechanism by which cholinesterase inhibitors treat the symptoms of Alzheimer's disease is accumulating. Certainly, as a class, the currently approved cholinesterase inhibitors (donepezil, galantamine, rivastigmine and tacrine) provide important benefits in patients with Alzheimer's disease and these drugs offer a significant advance in the management of dementia. [ABSTRACT FROM AUTHOR]

Explores the controversies surrounding the use of electroconvulsive therapy (ECT) in the treatment of life span depression in elderly people. Effectiveness of ECT; Impact of ECT on memory; Misconceptions about the use and side effects of ECT.

In this article the author discusses the effect of cholinesterase on vascular dementia (VaD). He cites the difference of the results of using cholinesterase inhibitors for the treatment of VaD and Alzheimer's disease (AD) patients. The author indicates the possibility of cholinesterase inhibitors to improve cognition and reduce rate of decline.

Comments on a study which investigated the use of haloperidol for agitation in dementia. Effectiveness of haloperidol on patients with dementia; Side effects which may have confounded any reductions in psychotic symptoms.

Background--Access to cardiac services is essential for appropriate implementation of evidence-based therapies to improve outcomes. The Cardiac Accessibility and Remoteness Index for Australia (Cardiac ARIA) aimed to derive an objective, geographic measure reflecting access to cardiac services. Methods and Results--An expert panel defined an evidence-based clinical pathway. Using Geographic Information Systems (GIS), the team developed a numeric/alphabetic index at 2 points along the continuum of care. The acute category (numeric) measured the time from the emergency call to arrival at an appropriate medical facility via road ambulance. The aftercare category (alphabetic) measured access to 4 basic services (family doctor, pharmacy, cardiac rehabilitation, and pathology services) when a patient returned to his or her community. The numeric index ranged from 1 (access to principal referral center with cardiac catheterization service < 1 hour) to 8 (no ambulance service, > 3 hours to medical facility, air transport required). The alphabetic index ranged from A (all 4 services available within a 1-hour drive-time) to E (no services available within 1 hour). The panel found that 13.9 million Australians (71%) resided within Cardiac ARIA 1A locations (hospital with cardiac catheterization laboratory and all aftercare within 1 hour). Those outside Cardiac 1A were overrepresented by people > 6 5 years of age (32%) and indigenous people (60%). Conclusions--The Cardiac ARIA index demonstrated substantial inequity in access to cardiac services in Australia. This methodology can be used to inform cardiology health service planning and could be applied to other common disease states within other regions of the world. INSET: CLINICAL PERSPECTIVE. [ABSTRACT FROM AUTHOR]