1,777 research outputs found
Perfused human organs versus Mary Shelley's Frankenstein
Novel drugs have to go through mandatory pre-clinical testing before they can be approved for use in clinical trials. In essence, it is a form of bench-to-bedside (N2B) translational medicine, but the wastage rate of target candidates is immensely high. Effects seen in vitro often do not translate to in vivo human settings. The search is on for better models closer to human physiology to be used in pre-clinical drug screening. The Ex Vivo Metrics© system has been introduced where a human organ is harvested and revitalized in a controlled environment suitable for testing of both drug efficacy and potential toxicity. This commentary expresses the author's views regarding this technology of perfused human organs
Excellent outcomes of laparoscopic esophagomyotomy for achalasia in patients older than 60Â years of age
The effectiveness of an esophagomyotomy for dysphagia in elderly patients with achalasia has been questioned. This study was designed to provide an answer.
A total of 162 consecutive patients with achalasia who had a laparoscopic myotomy and Dor fundoplication and who were available for follow-up interview were divided by age: <60Â years (range, 14â59; 118 patients), and â„60Â years (range, 60â93; 44 patients). Primary outcome measures were severity of dysphagia, regurgitation, heartburn, and chest pain before and after the operation as assessed on a four-point Likert scale, and the need for postoperative dilatation or revisional surgery.
Follow-up averaged 64Â months. Older patients had less dysphagia (mean score 3.6 vs. 3.9; PÂ <Â 0.01) and less chest pain (1.0 vs. 1.8; PÂ <Â 0.01). Regurgitation (3.0 vs. 3.2; PÂ =Â not significant (NS)) and heartburn (1.6 vs. 2.0, PÂ =Â NS) were similar. Older patients were no different in degree of esophageal dilation, manometric findings, number of previous pneumatic dilatations, or previous botulinum toxin therapy. None of the older patients had previously had an esophagomyotomy, whereas 14% of younger patients had (PÂ <Â 0.01).
After laparoscopic myotomy, older patients had better relief of dysphagia (mean score 1.0 vs 1.6; PÂ <Â 0.01), less heartburn (0.8 vs. 1.1; PÂ =Â 0.03), and less chest pain (0.2 vs. 0.8, PÂ <Â 0.01). Complication rates were similar. Older patients did not require more postoperative dilatations (22 patients vs. 10 patients; PÂ =Â 0.7) or revisional surgery for recurrent or persistent symptoms (3 vs. 1 patients; PÂ =Â 0.6). Satisfaction scores did not differ, and more than 90% of patients in both groups said in retrospect they would have undergone the procedure if they had known beforehand how it would turn out.
This retrospective review with long follow-up supports laparoscopic esophagomyotomy as first-line therapy in older patients with achalasia. They appeared to benefit even more than younger patients
General practitioner practice-based pharmacist input to medicines optimisation in the UK: pragmatic, multicenter, randomised, controlled trial
BACKGROUND: Changing demographics across the UK has led to general practitioners (GPs) managing increasing numbers of older patients with multi-morbidity and resultant polypharmacy. Through government led initiatives within the National Health Service, an increasing number of GP practices employ pharmacist support. The purpose of this study is to evaluate the impact of a medicines optimisation intervention, delivered by GP practice-based pharmacists, to patients at risk of medication-related problems (MRPs), on patient outcomes and healthcare costs. METHODS: A multi-centre, randomised (normal care or pharmacist supplemented care) study in four regions of the UK, involving patients (nâ=â356) from eight GP practices, with a 6-month follow-up period. Participants were adult patients who were at risk of MRPs. RESULTS: Median number of MRPs per intervention patient were reduced at the third assessment, i.e. 3 to 0.5 (pâ<â0.001) in patients who received the full intervention schedule. Medication Appropriateness Index (MAI) scores were reduced (medications more appropriate) for the intervention group, but not for control group patients (8 [4-13] to 5 [0-11] vs 8 [3-13] to 7 [3-12], respectively; pâ=â0.001). Using the intention-to-treat (ITT) approach, the number of telephone consultations in intervention group patients was reduced and different from the control group (1 [0-3] to 1 [0-2] vs 1 [0-2] to 1 [0-3], pâ=â0.020). No significant differences between groups were, however, found in unplanned hospital admissions, length of hospital stay, number of A&E attendances or outpatient visits. The mean overall healthcare cost per intervention patient fell from ÂŁ1041.7â±â1446.7 to ÂŁ859.1â±â1235.2 (pâ=â0.032). Cost utility analysis showed an incremental cost per patient of - ÂŁ229.0 (95% CI - 594.6, 128.2) and a mean QALY gained of 0.024 (95% CI - 0.021 to 0.065), i.e. indicative of a health status gain at a reduced cost (2016/2017). CONCLUSION: The pharmacist service was effective in reducing MRPs, inappropriateness of medications and telephone consultations in general practice in a cost-effective manner. TRIAL REGISTRATION: ClinicalTrials.Gov, NCT03241498. Registered 7 August 2017-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03241498
Cognitive Effects of Risperidone in Children with Autism and Irritable Behavior
Objective:
The objective of this research was to explore the effects of risperidone on cognitive processes in
children with autism and irritable behavior.
Method:
Thirty-eight children, ages 5-17 years with autism and severe behavioral disturbance, were
randomly assigned to risperidone (0.5 to 3.5 mg/day) or placebo for 8 weeks. This sample of 38 was a subset
of 101 subjects who participated in the clinical trial; 63 were unable to perform the cognitive tasks. A
double-blind placebo-controlled parallel groups design was used. Dependent measures included tests of
sustained attention, verbal learning, hand-eye coordination, and spatial memory assessed before, during, and
after the 8-week treatment. Changes in performance were compared by repeated measures ANOVA.
Results:
Twenty-nine boys and 9 girls with autism and severe behavioral disturbance and a mental age â„18
months completed the cognitive part of the study. No decline in performance occurred with risperidone.
Performance on a cancellation task (number of correct detections) and a verbal learning task (word
recognition) was better on risperidone than on placebo (without correction for multiplicity). Equivocal
improvement also occurred on a spatial memory task. There were no significant differences between
treatment conditions on the Purdue Pegboard (hand-eye coordination) task or the Analog Classroom Task
(timed math test).
Conclusion:
Risperidone given to children with autism at doses up to 3.5 mg for up to 8 weeks appears to have no
detrimental effect on cognitive performance
A Vast Thin Plane of Co-rotating Dwarf Galaxies Orbiting the Andromeda Galaxy
Dwarf satellite galaxies are thought to be the remnants of the population of
primordial structures that coalesced to form giant galaxies like the Milky Way.
An early analysis noted that dwarf galaxies may not be isotropically
distributed around our Galaxy, as several are correlated with streams of HI
emission, and possibly form co-planar groups. These suspicions are supported by
recent analyses, and it has been claimed that the apparently planar
distribution of satellites is not predicted within standard cosmology, and
cannot simply represent a memory of past coherent accretion. However, other
studies dispute this conclusion. Here we report the existence (99.998%
significance) of a planar sub-group of satellites in the Andromeda galaxy,
comprising approximately 50% of the population. The structure is vast: at least
400 kpc in diameter, but also extremely thin, with a perpendicular scatter
<14.1 kpc (99% confidence). Radial velocity measurements reveal that the
satellites in this structure have the same sense of rotation about their host.
This finding shows conclusively that substantial numbers of dwarf satellite
galaxies share the same dynamical orbital properties and direction of angular
momentum, a new insight for our understanding of the origin of these most dark
matter dominated of galaxies. Intriguingly, the plane we identify is
approximately aligned with the pole of the Milky Way's disk and is co-planar
with the Milky Way to Andromeda position vector. The existence of such
extensive coherent kinematic structures within the halos of massive galaxies is
a fact that must be explained within the framework of galaxy formation and
cosmology.Comment: Published in the 3rd Jan 2013 issue of Nature. 19 pages, 4 figures, 1
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