309 resultados para Enzyme replacement therapy
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Background Over the last two decades, Transcutaneous Bone-Anchored Prosthesis (TCBAP) has proven to be an effective alternative for prosthetic attachment for amputees, particularly for individuals unable to wear a socket. [1-17] However, the load transmitted through a typical TCBAP to the residual tibia and knee joint can be unbearable for transtibial amputees with knee arthritis. Aim A. To describe the surgical procedure combining TKR with TCBAP for the first time; and B. To present preliminary data on potential risks and benefits with assessment of clinical and functional outcomes at follow up Method We used a TCBAP connected to the tibial base plate of a Total Knee Replacement (TKR) prosthesis enabling the tibial residuum and the knee joint to act as weight sharing structures by transferring the load directly to the femur. We performed a standard hinged TKR connected to a custom made TCBAP at the first stage followed by creating a skin implant interface as a second stage. We retrospectively reviewed four cases of trans-tibial amputations presenting with knee joint arthritis. Patients were assessed clinically and functionally including standard measures of health-related quality of life, amputee mobility predictor tool, ambulation tests and actual activity level. Progress was monitored for 6-24 months. Results Clinical outcomes including adverse events show no major complications but one case of superficial infection. Functional outcomes improved for all participants as early as 6 months follow up. Discussion & Conclusion TKR and TCBAP were combined for the first time in this proof-of-concept case series. The preliminary outcomes indicated that this procedure is potentially a safe and effective alternative for this patient group despite the theoretical increase in risk of ascending infection through the skin-implant interface to the external environment. We suggest larger comparative series to further validate these results.
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Background Over the last two decades, Transcutaneous Bone-Anchored Prosthesis (TCBAP) has proven to be an effective alternative for prosthetic attachment for above knee amputees, particularly for individuals suffering from socket interface related complications. [1-17] Amputees with a very short femoral residuum (<15 cm) are at a considerable higher risk for these complications as well as high risk of implant failure, if they underwent a typical TCBAP due to the relatively small bony-implant contact leading to a need of a novel technique. Aim A. To describe the surgical procedure combining THR with TCBAP for the first time; and B. To present preliminary data on potential risks and benefits with assessment of clinical and functional outcomes at follow up Method We used a TCBAP connected to the stem of a Total Hip Replacement (THR) prosthesis enabling the femoral residuum and the hip joint to act as weight sharing structures by transferring the load directly to the pelvis. We performed a tri-polar THR connected to a custom made TCBAP at the first stage followed by creating a skin implant interface as a second stage. We retrospectively reviewed three cases of transfemoral amputations presenting with extremely short femoral residuum. Patients were assessed clinically and functionally including standard measures of health-related quality of life, amputee mobility predictor tool, ambulation tests and actual activity level. Progress was monitored for 6-24 months. Results Clinical outcomes including adverse events show no major complications. Functional outcomes improved for all participants as early as 6 months follow up. All cases were wheelchair bound preoperatively (K0 – AMPRO) improved to walking with One stick (K3 – AMPRO) at 3 months follow up. Discussion & Conclusion THR and TCBAP were combined for the first time in this proof-of-concept case series. The preliminary outcomes indicated that this procedure is potentially a safe and effective alternative despite the theoretical increase in risk of ascending infection through the skin-implant interface to the external environment for this patient group. We suggest larger comparative series to further validate these results.
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Introduction Lifestyle interventions might be useful in the management of adverse effects of androgen deprivation therapy (ADT) in men with prostate cancer. Objectives To examine the effects of dietary and exercise interventions on quality of life (QoL), metabolic risk factors and androgen deficiency symptoms in men with prostate cancer undergoing ADT. Methods CINAHL, Cochrane library, Medline and PsychINFO were searched to identify randomised controlled trials published from January, 2004 to October, 2014. Data extraction and methodological quality assessment was independently conducted by two reviewers. Meta-analysis was conducted using RevMan® 5.3.5. Results Of 2183 articles retrieved, 11 studies met the inclusion criteria and had low risk of bias.Nine studies evaluated exercise (resistance and/or aerobic and/or counselling) and three evaluated dietary supplementation. Median sample size =79 (33–121) and median intervention duration was 12 weeks (12–24). Exercise improved QoL measures (SMD 0.26, 95%CI −0.01 to 0.53) but not body composition, metabolic risk or vasomotor symptoms. Qualitative analysis indicated soy (or isoflavone) supplementation did not improve vasomotor symptoms; however, may improve QoL. Conclusions Few studies have evaluated the efficacy of lifestyle interventions in the management of adverse effects of ADT. We found inconclusive results for exercise in improving QoL and negative results for other outcomes. For soy-based products, we found negative results for modifying vasomotor symptoms and inconclusive results for improving QoL. Future work should investigate the best mode of exercise for improving QoL and other interventions such as dietary counselling should be investigated for their potential to modify these outcomes.
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The inflammatory skin disease pyoderma gangrenosum is characterized by destructive ulceration, typically occurring on the calves and thighs and less commonly on the buttocks and face. Lesions vary in size and may be multiple, often rapidly ulcerating to form deep painful wounds. Ulcers characteristically have ragged purple edges that overhang. In many patients a concomitant condition can be identified such as inflammatory bowel disease, rheumatoid arthritis, chronic autoimmune hepatitis, and various hematologic and solid tumours (1,2). Treatment of these ulcers in the past has been disappointing. The large lesions usually run a chronic course and heal very slowly, with traditional dressings often in combination with systemic steroids or immunosuppressants. Since 1998, a small number of case have been reported of adults with pyoderma gangrenosum whose lesions heal with the use of topical tacrolimus (FK506) (2–4). We report, to the best of our knowledge, the first successful treatment of a child with pyoderma gangrenosum using topical tacrolimus.
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This project investigates for the first time the biological mechanisms underlying the anecdotal use of Shikonin, an active component extracted from the Chinese herbal medicine "Zi Cao", as a treatment for hypertrophic scars. Compelling molecular and cellular evidence was generated supporting the therapeutic value of Shikonin as a scar treatment, suggesting that further development of this agent is warranted.
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Background: Inflammation and biomechanical factors have been associated with the development of vulnerable atherosclerotic plaques. Lipid-lowering therapy has been shown to be effective in stabilizing them by reducing plaque inflammation. Its effect on arterial wall strain, however, remains unknown. The aim of the present study was to investigate the role of high- and low-dose lipid-lowering therapy using an HMG-CoA reductase inhibitor, atorvastatin, on arterial wall strain. Methods and Results: Forty patients with carotid stenosis >40% were successfully followed up during the Atorvastatin Therapy: Effects on Reduction Of Macrophage Activity (ATHEROMA; ISRCTN64894118) Trial. All patients had plaque inflammation as shown by intraplaque accumulation of ultrasmall super paramagnetic particles of iron oxide on magnetic resonance imaging at baseline. Structural analysis was performed and change of strain was compared between high- and low-dose statin at 0 and 12 weeks. There was no significant difference in strain between the 2 groups at baseline (P=0.6). At 12 weeks, the maximum strain was significantly lower in the 80-mg group than in the 10-mg group (0.085±0.033 vs. 0.169±0.084; P=0.001). A significant reduction (26%) of maximum strain was observed in the 80-mg group at 12 weeks (0.018±0.02; P=0.01). Conclusions: Aggressive lipid-lowering therapy is associated with a significant reduction in arterial wall strain. The reduction in biomechanical strain may be associated with reductions in plaque inflammatory burden.
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Objectives: The aim of this study was to evaluate the effects of low-dose (10 mg) and high-dose (80 mg) atorvastatin on carotid plaque inflammation as determined by ultrasmall superparamagnetic iron oxide (USPIO)-enhanced carotid magnetic resonance imaging (MRI). The hypothesis was that treatment with 80 mg atorvastatin would demonstrate quantifiable changes in USPIO-enhanced MRI-defined inflammation within the first 3 months of therapy. Background: Preliminary studies indicate that USPIO-enhanced MRI can identify macrophage infiltration in human carotid atheroma in vivo and hence may be a surrogate marker of plaque inflammation. Methods: Forty-seven patients with carotid stenosis >40% on duplex ultrasonography and who demonstrated intraplaque accumulation of USPIO on MRI at baseline were randomly assigned in a balanced, double-blind manner to either 10 or 80 mg atorvastatin daily for 12 weeks. Baseline statin therapy was equivalent to 10 mg of atorvastatin or less. The primary end point was change from baseline in signal intensity (ΔSI) on USPIO-enhanced MRI in carotid plaque at 6 and 12 weeks. Results: Twenty patients completed 12 weeks of treatment in each group. A significant reduction from baseline in USPIO-defined inflammation was observed in the 80-mg group at both 6 weeks (ΔSI 0.13; p = 0.0003) and at 12 weeks (ΔSI 0.20; p < 0.0001). No difference was observed with the low-dose regimen. The 80-mg atorvastatin dose significantly reduced total cholesterol by 15% (p = 0.0003) and low-density lipoprotein cholesterol by 29% (p = 0.0001) at 12 weeks. Conclusions: Aggressive lipid-lowering therapy over a 3-month period is associated with significant reduction in USPIO-defined inflammation. USPIO-enhanced MRI methodology may be a useful imaging biomarker for the screening and assessment of therapeutic response to "anti-inflammatory" interventions in patients with atherosclerotic lesions. (Effects of Atorvastatin on Macrophage Activity and Plaque Inflammation Using Magnetic Resonance Imaging [ATHEROMA]; NCT00368589).
Evaluation of growth and changes in body composition following neonatal diagnosis of cystic fibrosis
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Early deficits in nutritional status that might require specific treatment and early response to nutritional therapy were studied longitudinally in 25 infants with cystic fibrosis (CF) diagnosed by neonatal screening, using anthropometric and research body composition methodology, and evaluation of pancreatic function. At the time of confirmed diagnosis (mean 5.4 weeks), body mass, length, total body fat (TBF), and total body potassium (TBK) were all significantly reduced. Following diagnosis and commencement of therapy there was a normalization of weight, length, and TBK by 6-12 months of age, indicating catch-up growth. But in some individuals the response was incomplete, and as a group, mean total body fat remained significantly lower than normal at 1 year of age. Seven of 25 (28%) were pancreatic sufficient at diagnosis, and all but one had evidence of declining pancreatic function requiring the institution of pancreatic enzyme therapy during the next 1-9 months. The median age of commencement of enzyme therapy was 10 weeks (range 5 weeks to 11 months). These longitudinal assessments emphasize the dynamic changes occurring in absorptive function, body composition, and nutritional status following neonatal diagnosis of cystic fibrosis and may reflect previously described abnormalities of energy metabolism in this age group. Abnormal body composition is evident in most CF infants following diagnosis by neonatal screening but pancreatic damage may still be evolving. We suggest that early active nutritional therapy and surveillance for changes in pancreatic function are warranted in CF infants diagnosed by neonatal screening.
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This study evaluates the effectiveness and social implications of home monitoring of 31 infants at risk of sudden infant death syndrome (SIDS). Thirteen siblings of children dying of SIDS, nine near miss SIDS infants and nine preterm infants with apnoea persisting beyond 40 weeks post conceptual age were monitored from a mean age of 15 days to a mean of 10 months. Chest movement detection monitors were used in 27 and thoracic impedance monitors in four. Genuine apnoeic episodes were reported by 21 families, and 13 infants required resuscitation. Apnoeic episodes occurred in all nine preterm infants but in only five (38%) of the siblings of SIDS (P<0.05). Troublesome false alarms were a major problem occurring with 61% of the infants and were more common with the preterm infants than the siblings of SIDS. All but two couples stated that the monitor decreased anxiety and improved their quality of life. Most parents accepted that the social restrictions imposed by the monitor were part of the caring process but four couples were highly resentful of the changes imposed on their lifestyle. The monitors used were far from ideal with malfunction occurring in 17, necessitating replacement in six, repair in six and cessation of monitoring in three. The parents became ingenious in modifying the monitors to their own individual requirements Although none of these 31 ‘at risk’ infants died the study sample was far too small to conclude whether home monitoring prevented any cases of SIDS.
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Purpose A retrospective planning study comparing volumetric arc therapy (VMAT) and stereotactic body radiotherapy (SBRT) treatment plans for non-small cell lung cancer (NSCLC). Methods and materials Five randomly selected early stage lung cancer patients were included in the study. For each patient, four plans were created: the SBRT plan and three VMAT plans using different optimisation methodologies. A total of 20 different plans were evaluated. The dose parameters of dose conformity results and the target dose constraints results were compared for these plans. Results The mean planning target volume (PTV) for all the plans (SBRT and VMAT) was 18·3 cm3, with a range from 15·6 to 20·1 cm3. The maximum dose tolerance to 1 cc of all the plans was within 140% (84 Gy) of the prescribed dose, and 95% of the PTV of all the plans received 100% of the prescribed dose (60 Gy). In all the plans, 99% of the PTV received a dose >90% of the prescribed dose, and the mean dose in all the plans ranged from 67 to 72 Gy. The planning target dose conformity for the SBRT and the VMAT (0°, 15° collimator single arc plans and dual arc) plans showed the tightness of the prescription isodose conformity to the target. Conclusions SBRT and VMAT are radiotherapy approaches that increase doses to small tumour targets without increasing doses to the organs at risk. Although VMAT offers an alternative to SBRT for NSCLC and the potential advantage of VMAT is the reduced treatment times over SBRT, the statistical results show that there was no significant difference between the SBRT and VMAT optimised plans in terms of dose conformity and organ-at-risk sparing.
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Replacement of deteriorated water pipes is a capital-intensive activity for utility companies. Replacement planning aims to minimize total costs while maintaining a satisfactory level of service and is usually conducted for individual pipes. Scheduling replacement in groups is seen to be a better method and has the potential to provide benefits such as the reduction of maintenance costs and service interruptions. However, developing group replacement schedules is a complex task and often beyond the ability of a human expert, especially when multiple or conflicting objectives need to be catered for, such as minimization of total costs and service interruptions. This paper describes the development of a novel replacement decision optimization model for group scheduling (RDOM-GS), which enables multiple group-scheduling criteria by integrating new cost functions, a service interruption model, and optimization algorithms into a unified procedure. An industry case study demonstrates that RDOM-GS can improve replacement planning significantly and reduce costs and service interruptions.
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Purpose: Emotional intelligence (EI) is an increasingly important aspect of a health professional’s skill set. It is strongly associated with empathy, reflection and resilience; all key aspects of radiotherapy practice. Previous work in other disciplines has formed contradictory conclusions concerning development of EI over time. This study aimed to determine the extent to which EI can develop during a radiotherapy undergraduate course and identify factors affecting this. Methods and materials: This study used anonymous coded Likert-style surveys to gather longitudinal data from radiotherapy students relating to a range of self-perceived EI traits during their 3-year degree. Data were gathered at various points throughout the course from the whole cohort. Results: A total of 26 students provided data with 14 completing the full series of datasets. There was a 17·2% increase in self-reported EI score with a p-value<0·0001. Social awareness and relationship skills exhibited the greatest increase in scores compared with self-awareness. Variance of scores decreased over time; there was a reduced change in EI for mature students who tended to have higher initial scores. EI increase was most evident immediately after clinical placements. Conclusions: Radiotherapy students increase their EI scores during a 3-year course. Students reported higher levels of EI immediately after their clinical placement; radiotherapy curricula should seek to maximise on these learning opportunities.
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BACKGROUND: The objective of this study was to describe prospectively quality of life (QOL) before and after radiotherapy for patients with prostate carcinoma. METHODS: Forty-three patients with T1-T3 prostate carcinoma who underwent conformal external beam radiation therapy were randomized either to the complete European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaire (EORTC QLQ-C30) or the Medical Outcomes Study Group Short Form Health Survey (SF-36) at baseline, at 3 weeks and 6 weeks after initial treatment, and at 6 weeks and 5 months after the completion of radiotherapy. The measures were self-reported patient QOL, and values are given as the mean +/- standard error of the mean. Changes in QOL are described from baseline to the end of treatment in both questionnaire groups. RESULTS: Emotional role functioning, as measured with the SF-36 questionnaire, significantly improved from 68.2 +/- 9.9 at baseline to 93.3 +/- 5.2 at the end of therapy (P = 0.02). The EORTC QLQ-C30 questionnaire revealed consistent values of emotional functioning during treatment (72.7 +/- 5.9 at baseline) but showed a significant improvement 6 weeks after therapy (89.0 +/- 4.4; P = 0.01). Role functioning deteriorated from 80.1 +/- 6.5 at baseline to 62.5 +/- 8.8 at the end of radiotherapy (P = 0.02). Symptoms of fatigue were shown to increase significantly from 26.9 +/- 6.0 at baseline to 37.7 +/- 7.6 at the end of therapy (P = 0.02). No significant changes in the other dimensions were observed in either questionnaire. CONCLUSIONS: After radiotherapy for prostate carcinoma, patients experience a temporary deterioration of fatigue and role functioning, as measured with the EORTC QLQ-C-30. Despite physical deterioration, the authors observed an improvement in emotional functioning scores with both questionnaires. This may have been due to psychological adaptation and coping.
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Background and purpose — Osseointegrated implants are an alternative for prosthetic attachment in individuals with amputation who are unable to wear a socket. However, the load transmitted through the osseointegrated fixation to the residual tibia and knee joint can be unbearable for those with transtibial amputation and knee arthritis. We report on the feasibility of combining total knee replacement (TKR) with an osseointegrated implant for prosthetic attachment. Patients and methods — We retrospectively reviewed all 4 cases (aged 38–77 years) of transtibial amputations managed with osseointegration and TKR in 2012–2014. The below-the-knee prosthesis was connected to the tibial base plate of a TKR, enabling the tibial residuum and knee joint to act as weight-sharing structures. A 2-stage procedure involved connecting a standard hinged TKR to custom-made implants and creation of a skin-implant interface. Clinical outcomes were assessed at baseline and after 1–3 years of follow-up using standard measures of health-related quality of life, ambulation, and activity level including the questionnaire for transfemoral amputees (Q-TFA) and the 6-minute walk test. Results — There were no major complications, and there was 1 case of superficial infection. All patients showed improved clinical outcomes, with a Q-TFA improvement range of 29–52 and a 6-minute walk test improvement range of 37–84 meters. Interpretation — It is possible to combine TKR with osseointegrated implants.
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Objective: We aimed to assess the feasibility of delivering a music therapy program on adolescent psychiatric wards. Method: We undertook a mixed-methods evaluation of a pilot program. Various active and receptive techniques were employed in group music therapy sessions delivered as part of a structured clinical program. Data collected in interviews with participants and staff and feedback questionnaires were thematically and descriptively analysed and triangulated. Results: Data from 62 questionnaires returned by 43 patients who took part in 16 music therapy sessions, and seven staff, evidenced strong support for music therapy. Patients typically reported experiencing sessions as relaxing, comforting, uplifting, and empowering; >90% would participate by choice and use music therapeutically in the future. Staff endorsed music therapy as valuable therapeutically, reporting that patients engaged enthusiastically and identified sessions as improving their own moods and ward milieu. Conclusions: Integration of music therapy in inpatient treatment of adolescents is feasible and acceptable, and is valued by staff and patients as a complement to ‘talking therapies’. Participation is enjoyed and associated with outcomes including improvement in mood, expression of feelings and social engagement consistent with recovery.