20 resultados para Grade of recommendation
Resumo:
Background
Inappropriate polypharmacy is a particular concern in older people and is associated with negative health outcomes. Choosing the best interventions to improve appropriate polypharmacy is a priority, hence interest in appropriate polypharmacy, where many medicines may be used to achieve better clinical outcomes for patients, is growing.
Objectives
This review sought to determine which interventions, alone or in combination, are effective in improving the appropriate use of polypharmacy and reducing medication-related problems in older people.
Search methods
In November 2013, for this first update, a range of literature databases including MEDLINE and EMBASE were searched, and handsearching of reference lists was performed. Search terms included 'polypharmacy', 'medication appropriateness' and 'inappropriate prescribing'.
Selection criteria
A range of study designs were eligible. Eligible studies described interventions affecting prescribing aimed at improving appropriate polypharmacy in people 65 years of age and older in which a validated measure of appropriateness was used (e.g. Beers criteria, Medication Appropriateness Index (MAI)).
Data collection and analysis
Two review authors independently reviewed abstracts of eligible studies, extracted data and assessed risk of bias of included studies. Study-specific estimates were pooled, and a random-effects model was used to yield summary estimates of effect and 95% confidence intervals (CIs). The GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach was used to assess the overall quality of evidence for each pooled outcome.
Main results
Two studies were added to this review to bring the total number of included studies to 12. One intervention consisted of computerised decision support; 11 complex, multi-faceted pharmaceutical approaches to interventions were provided in a variety of settings. Interventions were delivered by healthcare professionals, such as prescribers and pharmacists. Appropriateness of prescribing was measured using validated tools, including the MAI score post intervention (eight studies), Beers criteria (four studies), STOPP criteria (two studies) and START criteria (one study). Interventions included in this review resulted in a reduction in inappropriate medication usage. Based on the GRADE approach, the overall quality of evidence for all pooled outcomes ranged from very low to low. A greater reduction in MAI scores between baseline and follow-up was seen in the intervention group when compared with the control group (four studies; mean difference -6.78, 95% CI -12.34 to -1.22). Postintervention pooled data showed a lower summated MAI score (five studies; mean difference -3.88, 95% CI -5.40 to -2.35) and fewer Beers drugs per participant (two studies; mean difference -0.1, 95% CI -0.28 to 0.09) in the intervention group compared with the control group. Evidence of the effects of interventions on hospital admissions (five studies) and of medication-related problems (six studies) was conflicting.
Authors' conclusions
It is unclear whether interventions to improve appropriate polypharmacy, such as pharmaceutical care, resulted in clinically significant improvement; however, they appear beneficial in terms of reducing inappropriate prescribing.
Resumo:
Objective: To summarise the findings of an updated Cochrane review of interventions aimed at improving the appropriate use of polypharmacy in older people. Design: Cochrane systematic review. Multiple electronic databases were searched including MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (from inception to November 2013). Hand searching of references was also performed. Randomised controlled trials (RCTs), controlled clinical trials, controlled before-and-after studies and interrupted time series analyses reporting on interventions targeting appropriate polypharmacy in older people in any healthcare setting were included if they used a validated measure of prescribing appropriateness. Evidence quality was assessed using the Cochrane risk of bias tool and GRADE (Grades of Recommendation, Assessment, Development and Evaluation).
Setting: All healthcare settings.
Participants: Older people (≥65 years) with ≥1 long-term condition who were receiving polypharmacy (≥4 regular medicines).
Primary and secondary outcome measures: Primary outcomes were the change in prevalence of appropriate polypharmacy and hospital admissions. Medication-related problems (eg, adverse drug reactions), medication adherence and quality of life were included as secondary outcomes.
Results: 12 studies were included: 8 RCTs, 2 cluster RCTs and 2 controlled before-and-after studies. 1 study involved computerised decision support and 11 comprised pharmaceutical care approaches across various settings. Appropriateness was measured using validated tools, including the Medication Appropriateness Index, Beers’ criteria and Screening Tool of Older Person’s Prescriptions (STOPP)/ Screening Tool to Alert doctors to Right Treatment (START). The interventions demonstrated a reduction in inappropriate prescribing. Evidence of effect on hospital admissions and medication-related problems was conflicting. No differences in health-related quality of life were reported.
Conclusions: The included interventions demonstrated improvements in appropriate polypharmacy based on reductions in inappropriate prescribing. However, it remains unclear if interventions resulted in clinically significant improvements (eg, in terms of hospital admissions). Future intervention studies would benefit from available guidance on intervention development, evaluation and reporting to facilitate replication in clinical practice.
Resumo:
The object of this work is to assess the suitability of metallocene catalyzed linear low-density polyethylenes for the rotational molding of foams and to link the material and processing conditions to cell morphology and part mechanical properties (flexural and compressive strength). Through adjustments to molding conditions, the significant processing and physical material parameters that optimize metallocene catalyzed linear low-density polyethylene foam structure have been identified. The results obtained from an equivalent conventional grade of Ziegler-Natta catalyzed linear low-density polyethylene are used as a basis for comparison. The key findings of this study are that metallocene catalyzed LLDPE can be used in rotational foam molding to produce a foam that will perform as well as a ZieglerNatta catalyzed foam and that foam density Is by far the most Influential factor over mechanical properties of foam. © 2004 Society of Plastics Engineers.
Resumo:
The histological grading of cervical intraepithelial neoplasia (CIN) remains subjective, resulting in inter- and intra-observer variation and poor reproducibility in the grading of cervical lesions. This study has attempted to develop an objective grading system using automated machine vision. The architectural features of cervical squamous epithelium are quantitatively analysed using a combination of computerized digital image processing and Delaunay triangulation analysis; 230 images digitally captured from cases previously classified by a gynaecological pathologist included normal cervical squamous epithelium (n = 30), koilocytosis (n = 46), CIN 1 (n = 52), CIN 2 (n = 56), and CIN 3 (n=46). Intra- and inter-observer variation had kappa values of 0.502 and 0.415, respectively. A machine vision system was developed in KS400 macro programming language to segment and mark the centres of all nuclei within the epithelium. By object-oriented analysis of image components, the positional information of nuclei was used to construct a Delaunay triangulation mesh. Each mesh was analysed to compute triangle dimensions including the mean triangle area, the mean triangle edge length, and the number of triangles per unit area, giving an individual quantitative profile of measurements for each case. Discriminant analysis of the geometric data revealed the significant discriminatory variables from which a classification score was derived. The scoring system distinguished between normal and CIN 3 in 98.7% of cases and between koilocytosis and CIN 1 in 76.5% of cases, but only 62.3% of the CIN cases were classified into the correct group, with the CIN 2 group showing the highest rate of misclassification. Graphical plots of triangulation data demonstrated the continuum of morphological change from normal squamous epithelium to the highest grade of CIN, with overlapping of the groups originally defined by the pathologists. This study shows that automated location of nuclei in cervical biopsies using computerized image analysis is possible. Analysis of positional information enables quantitative evaluation of architectural features in CIN using Delaunay triangulation meshes, which is effective in the objective classification of CIN. This demonstrates the future potential of automated machine vision systems in diagnostic histopathology. Copyright (C) 2000 John Wiley and Sons, Ltd.
Resumo:
Background and purpose: Currently, optimal use of virtual simulation for all treatment sites is not entirely clear. This study presents data to identify specific patient groups for whom conventional simulation may be completely eliminated and replaced by virtual simulation. Sampling and method: Two hundred and sixty patients were recruited from four treatment sites (head and neck, breast, pelvis, and thorax). Patients were randomly assigned to be treated using the usual treatment process involving conventional simulation, or a treatment process differing only in the replacement of conventional plan verification with virtual verification. Data were collected on set-up accuracy at verification, and the number of unsatisfactory verifications requiring a return to the conventional simulator. A micro-economic costing analysis was also undertaken, whereby data for each treatment process episode were also collected: number and grade of staff present, and the time for each treatment episode. Results: The study shows no statistically significant difference in the number of returns to the conventional simulator for each site and study arm. Image registration data show similar quality of verification for each study arm. The micro-costing data show no statistical difference between the virtual and conventional simulation processes. Conclusions: At our institution, virtual simulation including virtual verification for the sites investigated presents no disadvantage compared to conventional simulation.
Resumo:
Three experiments were conducted to test the effectiveness of different footbath solutions and regimens in the treatment of digital dermatitis (DD) in dairy cows. During the study, groups of cows walked through allocated footbath solutions after milking on 4 consecutive occasions. All cows were scored weekly for DD lesion stage on the hind feet during milking. A “transition grade” was assigned on the basis of whether the DD lesions improved (1) or deteriorated or did not improve (0) from week to week. This grade per cow was averaged for all cows in the group. In experiment 1, 118 cows were allocated to 1 of 3 footbath treatments for 5 wk: (1) 5% CuSO4 each week, (2) 2% ClO- each week, or (3) no footbath (control). The mean transition grade, and proportion of cows without DD lesions at the end of the trial were significantly higher for treatment 1 above (0.36, 0.13, and 0.11, respectively; standard error of the difference, SED=0.057). In experiment 2, 117 cows were allocated to 1 of 4 footbath treatment regimens for 8 wk: (1) 5% CuSO4 each week, (2) 2% CuSO4 each week, (3) 5% CuSO4 each fortnight, or (4) 2% CuSO4 each fortnight. For welfare reasons, cows allocated to the weekly and fortnightly footbath regimens had an average prevalence of >60% and =25% active DD at the start of the trial, respectively. Significantly more cows had no DD lesions (0.53 vs. 0.36, respectively; SED=0.049), and the mean transition grade of DD lesions was higher in the 5% compared with the 2% weekly CuSO4 treatment (0.52 vs. 0.38, respectively; SED=0.066). Similarly, significantly more cows had no DD lesions in the 5% compared with the 2% fortnightly CuSO4 treatments (0.64 vs. 0.47, respectively; SED=0.049). In experiment 3, 95 cows were allocated to 1 of 3 footbath treatments: (1) each week alternating 5% CuSO4 with 10% salt water, (2) each week alternating 5% CuSO4 with water, or (3) 5% CuSO4 each fortnight (control). After 10 wk, more cows had no DD in the salt water treatment than in the control treatment (0.35 vs. 0.26, respectively; SED=0.038), but levels of active lesions were higher for this treatment than in the other 2 treatments (0.17, 0.00, and 0.13, respectively; SED=0.029). Treatment did not affect mean transition grade of DD lesions. In conclusion, CuSO4 was the only footbath solution that was consistently effective for treatment of DD. In cases when DD prevalence was high, a footbath each week using 5% CuSO4 was the most effective treatment.
Resumo:
The recent identification of somatic mutations in the catalytic region of PIK3 (PIK3CA) in breast cancer and demonstration of their oncogenic function has implicated PIK3CA in mammary carcinogenesis. To investigate possible ethnic differences in patterns of PIK3CA mutations in Singaporean Chinese breast cancer and to characterize these in a panel of cell lines, we sequenced exons 9 and 20 in 80 primary tumors, 19 breast cancer cell lines and 7 normal human mammary epithelial cells (HMECs). Searching for novel hotspots of mutation, we sequenced additional exons ( 1, 2, 6, 7, 14 and 18) in 20 primary tumors and 6 breast cancer cell lines. We detected 33 point mutations in 31 of 80 (39%) breast cancers, and 11 mutations in 10 of 19 (53%) breast cancer cell lines. No mutations were detected in normal breast tissue adjacent to the tumor, or in the 6 normal HMECs. The exon 20 A3140G (H1047R) substitution was identified most frequently (22/31, 71%) and showed a significant association with patient age ( p = 0.043) and stage of the disease ( p = 0.025), but not with ER/PR status or histological grade of the tumor. The incidence of point mutations in PIK3CA, the A3140G substitution in particular, in Singapore breast cancers are among the most frequent reported to date for any gene in breast cancer. The results suggest that mutation of PIK3CA might contribute to development of early stage breast cancer and could provide a potent target for early diagnosis and therapy.
Resumo:
Background: AGI004 is a controlled-release transdermal patch preparation of mecamylamine. We conducted a randomised placebo-controlled phase II study of two dose levels of AGI004 in chemotherapy-induced diarrhoea (CID).
Methods: Adult patients receiving chemotherapy who had experienced diarrhoea (NCI grade 1-2) during previous cycles of chemotherapy were eligible. In all, 64 patients were randomised to receive AGI004 4mg then 8mg per 24 h transdermal patch or placebo for two sequential cycles of chemotherapy. Patients' severity of diarrhoea was physician-assessed using NCI grade of diarrhoea and patient-assessed using information recorded in daily diaries of bowel movements.
Results: Overall AGI004 doubled the odds of a response to treatment on the first day of chemotherapy based on physician assessment of NCI grade of diarrhoea compared with placebo (odds ratio = 2.0, 90% confidence interval: 0.9-4.5) and there was a trend to improved response rates for AGI004 for the full treatment cycle although these results were not statistically significant. There was also evidence of significantly improved response rates based on patient assessment of diarrhoea both overall (P = 0.05) and at the 8-mg dose level (P = 0.02) compared with placebo.
Conclusion: AGI004 demonstrated effectiveness in reducing chemotherapy-associated diarrhoea, with results suggesting response across multiple measurements of diarrhoea. Treatment was well tolerated with no drug-related adverse events. Further evaluation of this agent in the management of CID is warranted.
Resumo:
Background: Barrett's oesophagus (BO) is a well recognized precursor of the majority of cases of oesophageal adenocarcinoma (OAC). Endoscopic surveillance of BO patients is frequently undertaken in an attempt to detect early OAC, high grade dysplasia (HGD) or low grade dysplasia (LGD). However histological interpretation and grading of dysplasia is subjective and poorly reproducible. The alternative flow cytometry and cytology-preparation image cytometry techniques require large amounts of tissue and specialist expertise which are not widely available for frontline health care.
Methods: This study has combined whole slide imaging with DNA image cytometry, to provide a novel method for the detection and quantification of abnormal DNA contents. 20 cases were evaluated, including 8 Barrett's specialised intestinal metaplasia (SIM), 6 LGD and 6 HGD. Feulgen stained oesophageal sections (1µm thickness) were digitally scanned in their entirety and evaluated to select regions of interests and abnormalities. Barrett’s mucosa was then interactively chosen for automatic nuclei segmentation where irrelevant cell types are ignored. The combined DNA content histogram for all selected image regions was then obtained. In addition, histogram measurements, including 5c exceeding ratio (xER-5C), 2c deviation index (2cDI) and DNA grade of malignancy (DNA-MG), were computed.
Results: The histogram measurements, xER-5C, 2cDI and DNA-MG, were shown to be effective in differentiating SIM from HGD, SIM from LGD, and LGD from HGD. All three measurements discriminated SIM from HGD cases successfully with statistical significance (pxER-5C=0.0041, p2cDI=0.0151 and pDNA-MG=0.0057). Statistical significance is also achieved differentiating SIM from LGD samples with pxER-5C=0.0019, p2cDI=0.0023 and pDNA-MG=0.0030. Furthermore the differences between LGD and HGD cases are statistical significant (pxER-5C=0.0289, p2cDI=0.0486 and pDNA-MG=0.0384).
Conclusion: Whole slide image cytometry is a novel and effective method for the detection and quantification of abnormal DNA content in BO. Compared to manual histological review, this proposed method is more objective and reproducible. Compared to flow cytometry and cytology-preparation image cytometry, the current method is low cost, simple to use and only requires a single 1µm tissue section. Whole slide image cytometry could assist the routine clinical diagnosis of dysplasia in BO, which is relevant for future progression risk to OAC.
Resumo:
In this work, a highly instrumented single screw extruder has been used to study the effect of polymer rheology on the thermal efficiency of the extrusion process. Three different molecular weight grades of high density polyethylene (HDPE) were extruded at a range of conditions. Three geometries of extruder screws were used at several set temperatures and screw rotation speeds. The extruder was equipped with real-time quantification of energy consumption; thermal dynamics of the process were examined using thermocouple grid sensors at the entrance to the die. Results showed that polymer rheology had a significant effect on process energy consumption and thermal homogeneity of the melt. Highest specific energy consumption and poorest homogeneity was observed for the highest viscosity grade of HDPE. Extruder screw geometry, set extrusion temperature and screw rotation speed were also found to have a direct effect on energy consumption and melt consistency. In particular, specific energy consumption was lower using a barrier flighted screw compared to single flighted screws at the same set conditions. These results highlight the complex nature of extrusion thermal dynamics and provide evidence that rheological properties of the polymer can significantly influence the thermal efficiency of the process.
Resumo:
The purpose of this research study was to investigate and identify possible patterns relating to academic performance on the effects of university students self-selecting where to sit in a lecture theatre.
The key research questions are:
1. Does seating position affect student performance?
2. Do the most academically able and engaged students regularly sit at the front of lecture theatres?
Academic achievement
Preliminary results suggest significant assessment score differences between those that sit at the front and those that sit further the back. Of those that received a grade of 75%+ (Grade A) 6.67% regularly sat at the back. With the same group 46.67% regularly sat at the front. Of the group that scored less than 50% (Grade D) 0% of students regularly sat at the front. 12.50% regularly sat in the middle zones with 37.50% sitting at the back. It was also observed that the remaining numbers did not consistently sit in the same zone.
Temporal movement
There is little evidence of movement between seating zones of the Grade A group throughout the 24 week period. However there was considerable movement with the Grade D group. Although still under analysis there appears be a pattern of students in this group graduating towards the back seating positions over the course of the programme.
Engagement
The frequency of completed entries on PinPoint was also used as an indicator of engagement. With the Grade A group 75% of them regularly completed an entry whereas in the Grade D group this drops to less than 50%.
Further analysis on the attitudinal factors in relational to seating position and performance are ongoing, but preliminary results suggest that those students that scored highly in attitude tended to sit at the front and middle sections.
It would indeed appear that the more highly engaged and academically capable students voluntarily sit at the front for most lectures. Interestingly as the course progresses those who had lesser engagement and below average midterm results tend to began to sit progressively toward the back. If this is a repeatable pattern then a linear regression analysis of the seating positions and midterm results could help predict students in danger of failing.
Resumo:
BACKGROUND: In the previously reported ALSYMPCA trial in patients with castration-resistant prostate cancer and symptomatic bone metastases, overall survival was significantly longer in patients treated with radium-223 dichloride (radium-223) than in patients treated with placebo. In this study, we investigated safety and overall survival in radium-223 treated patients in an early access programme done after the ALSYMPCA study and before regulatory approval of radium-223.
METHODS: We did an international, prospective, interventional, open-label, single-arm, phase 3b study. Enrolled patients were aged 18 years or older with histologically or cytologically confirmed progressive bone-predominant metastatic castration-resistant prostate cancer with two or more skeletal metastases on imaging (with no restriction as to whether they were symptomatic or asymptomatic; without visceral disease but lymph node metastases were allowed). Patients received intravenous injections of radium-223, 50 kBq/kg (current recommendation 55 kBq/kg after implementation of National Institute of Standards and Technology update on April 18, 2016) every 4 weeks for up to six injections. Other concomitant anticancer therapies were allowed. Primary endpoints were safety and overall survival. The safety and efficacy analyses were done on all patients who received at least one dose of the study drug. The study has been completed, and we report the final analysis here. This study is registered with ClinicalTrials.gov, number NCT01618370, and the European Union Clinical Trials Register, EudraCT number 2012-000075-16.
FINDINGS: Between July 22, 2012, and Dec 19, 2013, 839 patients were enrolled from 113 sites in 14 countries. 696 patients received one or more doses of radium-223; 403 (58%) of these patients had all six planned injections. Any-grade treatment-emergent adverse events occurred in 523 (75%) of 696 patients; any-grade treatment-emergent adverse events deemed to be related to treatment were reported in 281 (40%) patients. The most common grade 3 or worse treatment-related treatment-emergent adverse events were anaemia in 32 (5%) patients, thrombocytopenia in 15 (2%) patients, neutropenia in ten (1%) patients, and leucopenia in nine (1%) patients. Any grade of serious adverse events were reported in 243 (35%) patients. Median follow-up was 7·5 months (IQR 5-11) and 210 deaths were reported; median overall survival was 16 months (95% CI 13-not available [NA]). In an exploratory analysis of overall survival with predefined factors, median overall survival was longer for: patients with baseline alkaline phosphatase concentration less than the upper limit of normal (ULN; median NA, 95% CI 16 months-NA) than for patients with an alkaline phosphatase concentration equal to or greater than the ULN (median 12 months, 11-15); patients with baseline haemoglobin levels 10 g/dL or greater (median 17 months, 14-NA) than for patients with haemoglobin levels less than 10 g/dL (median 10 months, 8-14); patients with a baseline Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 (median NA, 17 months-NA) than for patients with an ECOG PS of 1 (median 13 months, 11-NA) or an ECOG PS of 2 or more (median 7 months, 5-11); and for patients with no reported baseline pain (median NA, 16 months-NA) than for those with mild pain (median 14 months, 13-NA) or moderate-severe pain (median 11 months, 9-13). Median overall survival was also longer in patients who received radium-223 plus abiraterone, enzalutamide, or both (median NA, 95% CI 16 months-NA) than in those who did not receive these agents (median 13 months, 12-16), and in patients who received radium-223 plus denosumab (median NA, 15 months-NA) than in patients who received radium-223 without denosumab (median 13 months, 12-NA).
INTERPRETATION: Our findings show that radium-223 can be safely combined with abiraterone or enzalutamide, which are now both part of the standard of care for patients with metastatic castration-resistant prostate cancer. Furthermore, our findings extend to patients who were asymptomatic at baseline, unlike those enrolled in the pivotal ALSYMPCA study. The findings of prolonged survival in patients treated with concomitant abiraterone, enzalutamide, or denosumab require confirmation in prospective randomised trials.
FUNDING: Pharmaceutical Division of Bayer.
Resumo:
Rotomolded containers for solvents and hydrocarbons require the use of high-permeability resins such as polyamide (PA). The published studies with this material are very scarce. In this work, a commercial grade of PA11 was rotational-molded using different processing temperatures and characterized with a range of techniques. The study aims at investigating the influence of the processing conditions on the microstructure and properties of molded parts. The results showed that the spherulitic morphology and the mechanical properties are affected by the processing temperature, the optimum processing range being between 220°C and 240°C. Overheating causes a decrease of the impact strength and a severe increase in the formation of pinholes at the outer surface due to polymer degradation and formation of volatile products. The thermo-oxidation reactions occurring at the inner surface of the samples result in the formation of products that absorb in the UV and visible light regions and cause the microhardness and the melt viscosity of the material to increase. The extent and severity of the degradation at the inner surface may be easily assessed by fluorescence microscopy. © 2008 Wiley Periodicals, Inc.
Resumo:
The British Association for Psychopharmacology (BAP) coordinated a meeting of experts to review and revise its first (2006) Guidelines for clinical practice with anti-dementia drugs. As before, levels of evidence were rated using accepted standards which were then translated into grades of recommendation A to D, with A having the strongest evidence base (from randomized controlled trials) and D the weakest (case studies or expert opinion). Current clinical diagnostic criteria for dementia have sufficient accuracy to be applied in clinical practice (B) and brain imaging can improve diagnostic accuracy (B). Cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) are effective for mild to moderate Alzheimer's disease (A) and memantine for moderate to severe Alzheimer's disease (A). Until further evidence is available other drugs, including statins, anti-inflammatory drugs, vitamin E and Ginkgo biloba, cannot be recommended either for the treatment or prevention of Alzheimer's disease (A). Neither cholinesterase inhibitors nor memantine are effective in those with mild cognitive impairment (A). Cholinesterase inhibitors are not effective in frontotemporal dementia and may cause agitation (A), though selective serotonin reuptake inhibitors may help behavioural (but not cognitive) features (B). Cholinesterase inhibitors should be used for the treatment of people with Lewy body dementias (Parkinson's disease dementia and dementia with Lewy bodies (DLB)), especially for neuropsychiatric symptoms (A). Cholinesterase inhibitors and memantine can produce cognitive improvements in DLB (A). There is no clear evidence that any intervention can prevent or delay the onset of dementia. Although the consensus statement focuses on medication, psychological interventions can be effective in addition to pharmacotherapy, both for cognitive and non-cognitive symptoms. Many novel pharmacological approaches involving strategies to reduce amyloid and/or tau deposition are in progress. Although results of pivotal studies are awaited, results to date have been equivocal and no disease-modifying agents are either licensed or can be currently recommended for clinical use.