PASSIVE IMMUNOTHERAPY - A VIABLE TREATMENT FOR ALZHEIMER\u27S DISEASE

Passive immunotherapy is one of the most exciting and extensively researched areas in the field of Alzheimer’s disease (AD) today, harbouring the potential to become the first disease-modifying treatment for the disease. The interest in immunotherapy as a treatment stemmed from the significant dangers of toxic side-effects and major obstacles in selectivity for currently pursued therapies against amyloid beta (Aβ) proteins and neurofibrillary tangles. Passive immunotherapy especially, has received much limelight, seen as having the potential to be the safer alternative to active immunisation which encountered a significant setback with the notorious AN-1972 trial in which 6% of the vaccinated patients developed meningoencephalitis. At present, passive immunisation research in animal models have exclusively focused on targeting Aβ proteins, a widely accepted pathology of AD.Following on from this, the preliminary results of phase II trials of three distinct passive immunisation strategies were demonstrated at the 2008 International Conference on Alzheimer’s Disease (ICAD). The three therapeutic strategies each targeted the N-terminal of Aβ, the central epitope or utilised a polyclonal approach. The results demonstrated potential as well as caution. Efficacy was undoubtedly present but not to the extent that was hoped and side-effects, most notably vasogenic oedema occurred in the N-terminal targeting antibody, bapineuzimab. Lessons have been learnt by identifying the possible cause of the problems and have been taken on board to nurture the proven efficacious results. Key points to be addressed currently are dosage of the agent to ensure that high enough concentrations enter the central nervous system to be available to cause effect and early enough time of administration to cause effect. The results of the efficacy and safety phase III trials and the development of newer passive immunotherapeutic agents addressing the problems are eagerly awaited in the hope of finally yielding a disease modifying therapy of AD

THE IMPACT OF GUIDANCE ON CITALOPRAM’S EFFECTS ON THE QT PERIOD ON THE PRACTICE OF CLINICIANS

In 2011, the FDA published guidelines regarding the prescribing of citalopram and escitalopram following publication of evidence showing prolongation of the QT period at therapeutic doses. This paper looked at the impact of these guidelines on the prescribing practices of clinicians in one centre. It showed that clinicians have changed practices in accordance with the guidelines for citalopram but no clear patterns were seen in escitalopram or when looking individually at thespecific guidelines for patients over 60 years of age. There was no evidence of increased concordance by clinicians with the guidelines in patients taking other QT prolonging drugs who are at additional risk. Overall, the guidelines have made an impact on practice but this is partial and2% of all patients still remain on regimes that do not fit the guidelines. The possible reasons for this are explored

Development and validation of a MEDLINE search filter/hedge for degenerative cervical myelopathy

Abstract Background Degenerative cervical myelopathy (DCM) is a common condition with many unmet clinical needs. Pooled analysis of studies is an important tool for advancing medical understanding. This process starts with a systematic search of the literature. Identification of studies in DCM is challenged by a number of factors, including non-specific terminology and index terms. Search filters or HEDGEs, are search strings developed and validated to optimise medical literature searches. We aimed to develop a search filter for DCM for the MEDLINE database. Methods The diagnostic test assessment framework of a “development dataset” and seperate “validation dataset” was used. The development dataset was formed by hand searching four leading spinal journals (Spine, Journal of Neurosurgery Spine, Spinal Cord and Journal of Spinal Disorders and Techniques) in 2005 and 2010. The search filter was initially developed focusing on sensitivity and subsequently refined using NOT functions to improve specificity. One validation dataset was formed from DCM narrative and systematic review articles and the second, articles published in April of 1989, 1993, 1997, 2001, 2005, 2009, 2013 and 2017 retrieved via the search MeSH term ‘Spine’. Metrics of sensitivity, specificity, precision and accuracy were used to test performance. Results Hand searching identified 77/1094 relevant articles for 2005 and 55/1199 for 2010. We developed a search hedge with 100% sensitivity and a precision of 30 and 29% for the 2005 and 2010 development datasets respectively. For the selected time periods, EXP Spine returned 2113 publications and 30 were considered relevant. The search filter identified all 30 relevant articles, with a specificity of 94% and precision of 20%. Of the 255 references listed in the narrative index reviews, 225 were indexed in MEDLINE and 165 (73%) were relevant articles. All relevant articles were identified and accuracy ranged from 67 to 97% over the three reviews. Of the 42 articles returned from 3 recent systematic reviews, all were identified by the filter. Conclusions We have developed a highly sensitive hedge for the research of DCM. Whilst precision is similarly low as other hedges, this search filter can be used as an adjunct for DCM search strategies

PASSIVE IMMUNOTHERAPY - A VIABLE TREATMENT FOR ALZHEIMER\u27S DISEASE

Passive immunotherapy is one of the most exciting and extensively researched areas in the field of Alzheimer’s disease (AD) today, harbouring the potential to become the first disease-modifying treatment for the disease. The interest in immunotherapy as a treatment stemmed from the significant dangers of toxic side-effects and major obstacles in selectivity for currently pursued therapies against amyloid beta (Aβ) proteins and neurofibrillary tangles. Passive immunotherapy especially, has received much limelight, seen as having the potential to be the safer alternative to active immunisation which encountered a significant setback with the notorious AN-1972 trial in which 6% of the vaccinated patients developed meningoencephalitis. At present, passive immunisation research in animal models have exclusively focused on targeting Aβ proteins, a widely accepted pathology of AD.Following on from this, the preliminary results of phase II trials of three distinct passive immunisation strategies were demonstrated at the 2008 International Conference on Alzheimer’s Disease (ICAD). The three therapeutic strategies each targeted the N-terminal of Aβ, the central epitope or utilised a polyclonal approach. The results demonstrated potential as well as caution. Efficacy was undoubtedly present but not to the extent that was hoped and side-effects, most notably vasogenic oedema occurred in the N-terminal targeting antibody, bapineuzimab. Lessons have been learnt by identifying the possible cause of the problems and have been taken on board to nurture the proven efficacious results. Key points to be addressed currently are dosage of the agent to ensure that high enough concentrations enter the central nervous system to be available to cause effect and early enough time of administration to cause effect. The results of the efficacy and safety phase III trials and the development of newer passive immunotherapeutic agents addressing the problems are eagerly awaited in the hope of finally yielding a disease modifying therapy of AD

THE IMPACT OF GUIDANCE ON CITALOPRAM’S EFFECTS ON THE QT PERIOD ON THE PRACTICE OF CLINICIANS

In 2011, the FDA published guidelines regarding the prescribing of citalopram and escitalopram following publication of evidence showing prolongation of the QT period at therapeutic doses. This paper looked at the impact of these guidelines on the prescribing practices of clinicians in one centre. It showed that clinicians have changed practices in accordance with the guidelines for citalopram but no clear patterns were seen in escitalopram or when looking individually at thespecific guidelines for patients over 60 years of age. There was no evidence of increased concordance by clinicians with the guidelines in patients taking other QT prolonging drugs who are at additional risk. Overall, the guidelines have made an impact on practice but this is partial and2% of all patients still remain on regimes that do not fit the guidelines. The possible reasons for this are explored

Development and validation of a MEDLINE search filter/hedge for degenerative cervical myelopathy

Abstract Background Degenerative cervical myelopathy (DCM) is a common condition with many unmet clinical needs. Pooled analysis of studies is an important tool for advancing medical understanding. This process starts with a systematic search of the literature. Identification of studies in DCM is challenged by a number of factors, including non-specific terminology and index terms. Search filters or HEDGEs, are search strings developed and validated to optimise medical literature searches. We aimed to develop a search filter for DCM for the MEDLINE database. Methods The diagnostic test assessment framework of a “development dataset” and seperate “validation dataset” was used. The development dataset was formed by hand searching four leading spinal journals (Spine, Journal of Neurosurgery Spine, Spinal Cord and Journal of Spinal Disorders and Techniques) in 2005 and 2010. The search filter was initially developed focusing on sensitivity and subsequently refined using NOT functions to improve specificity. One validation dataset was formed from DCM narrative and systematic review articles and the second, articles published in April of 1989, 1993, 1997, 2001, 2005, 2009, 2013 and 2017 retrieved via the search MeSH term ‘Spine’. Metrics of sensitivity, specificity, precision and accuracy were used to test performance. Results Hand searching identified 77/1094 relevant articles for 2005 and 55/1199 for 2010. We developed a search hedge with 100% sensitivity and a precision of 30 and 29% for the 2005 and 2010 development datasets respectively. For the selected time periods, EXP Spine returned 2113 publications and 30 were considered relevant. The search filter identified all 30 relevant articles, with a specificity of 94% and precision of 20%. Of the 255 references listed in the narrative index reviews, 225 were indexed in MEDLINE and 165 (73%) were relevant articles. All relevant articles were identified and accuracy ranged from 67 to 97% over the three reviews. Of the 42 articles returned from 3 recent systematic reviews, all were identified by the filter. Conclusions We have developed a highly sensitive hedge for the research of DCM. Whilst precision is similarly low as other hedges, this search filter can be used as an adjunct for DCM search strategies

Development and validation of a MEDLINE search filter/hedge for degenerative cervical myelopathy

Abstract Background Degenerative cervical myelopathy (DCM) is a common condition with many unmet clinical needs. Pooled analysis of studies is an important tool for advancing medical understanding. This process starts with a systematic search of the literature. Identification of studies in DCM is challenged by a number of factors, including non-specific terminology and index terms. Search filters or HEDGEs, are search strings developed and validated to optimise medical literature searches. We aimed to develop a search filter for DCM for the MEDLINE database. Methods The diagnostic test assessment framework of a “development dataset” and seperate “validation dataset” was used. The development dataset was formed by hand searching four leading spinal journals (Spine, Journal of Neurosurgery Spine, Spinal Cord and Journal of Spinal Disorders and Techniques) in 2005 and 2010. The search filter was initially developed focusing on sensitivity and subsequently refined using NOT functions to improve specificity. One validation dataset was formed from DCM narrative and systematic review articles and the second, articles published in April of 1989, 1993, 1997, 2001, 2005, 2009, 2013 and 2017 retrieved via the search MeSH term ‘Spine’. Metrics of sensitivity, specificity, precision and accuracy were used to test performance. Results Hand searching identified 77/1094 relevant articles for 2005 and 55/1199 for 2010. We developed a search hedge with 100% sensitivity and a precision of 30 and 29% for the 2005 and 2010 development datasets respectively. For the selected time periods, EXP Spine returned 2113 publications and 30 were considered relevant. The search filter identified all 30 relevant articles, with a specificity of 94% and precision of 20%. Of the 255 references listed in the narrative index reviews, 225 were indexed in MEDLINE and 165 (73%) were relevant articles. All relevant articles were identified and accuracy ranged from 67 to 97% over the three reviews. Of the 42 articles returned from 3 recent systematic reviews, all were identified by the filter. Conclusions We have developed a highly sensitive hedge for the research of DCM. Whilst precision is similarly low as other hedges, this search filter can be used as an adjunct for DCM search strategies

Additional file 1: of Development and validation of a MEDLINE search filter/hedge for degenerative cervical myelopathy

Final, validated search filter for DCM in MEDLINE. (DOCX 15 kb

Trend and Seasonality of Diabetic Foot Amputation in South Korea: A Population-Based Nationwide Study

The number of lower extremity amputations in diabetic foot patients in Korea is increasing annually. In this nationwide population-based retrospective study, we investigated the data of 420,096 diabetes mellitus patients aged ≥18 years using the Korean Health Insurance Review and Assessment Service claim database. We aimed to study the seasonal and monthly trends in diabetic foot amputations in Korea. After applying the inclusion criteria, 8156 amputation cases were included. The analysis showed an increasing trend in monthly amputation cases. In terms of seasonality, the monthly frequency of amputation was commonly observed to be lower in February and September every year. Diabetic foot amputations frequently occurred in March, July, and November. There was no difference between the amputation frequency and mean temperature/humidity. This study is meaningful as it is the first nationwide study in Korea to analyze the seasonal and monthly trends in diabetic foot amputation in relation to climatic factors. In conclusion, we recognize an increased frequency of amputation in March, July, and November and recommend intensive educational program on foot care for all diabetes patients and their caregivers. This could improve wound management and amputation prevention guidelines for diabetic foot patients in the Far East with information on dealing with various seasonal changes