171 research outputs found

    Inappropriate prescribing and adverse drug events in older people

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    Inappropriate prescribing (IP) in older patients is highly prevalent and is associated with an increased risk of adverse drug events (ADEs), morbidity, mortality and healthcare utilisation. Consequently, IP is a major safety concern and with changing population demographics, it is likely to become even more prevalent in the future. IP can be detected using explicit or implicit prescribing indicators. Theoretically, the routine clinical application of these IP criteria could represent an inexpensive and time efficient method to optimise prescribing practice. However, IP criteria must be sensitive, specific, have good inter-rater reliability and incorporate those medications most commonly associated with ADEs in older people. To be clinically relevant, use of prescribing appropriateness tools must translate into positive patient outcomes, such as reduced rates of ADEs. To accurately measure these outcomes, a reliable method of assessing the relationship between the administration of a drug and an adverse clinical event is required. The Naranjo criteria are the most widely used tool for assessing ADE causality, however, they are often difficult to interpret in the context of older patients. ADE causality criteria that allow for the multiple co-morbidities and prescribed medications in older people are required. Ultimately, the current high prevalence of IP and ADEs is unacceptable. IP screening criteria need to be tested as an intervention to assess their impact on the incidence of ADEs in vulnerable older patients. There is a role for IP screening tools in everyday clinical practice. These should enhance, not replace good clinical judgement, which in turn should be based on sound pharmacogeriatric training

    Magnitude of potentially inappropriate prescribing in Germany among older patients with generalized anxiety disorder

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    <p>Abstract</p> <p>Background</p> <p>Several medications commonly used to treat generalized anxiety disorder (GAD) have been designated "potentially inappropriate" for use in patients aged ≥65 years because their risks may outweigh their potential benefits. The actual extent of use of these agents in clinical practice is unknown, however.</p> <p>Methods</p> <p>Using a database with information from encounters with general practitioners (GP) in Germany, we identified all patients, aged ≥65 years, with any GP office visits or dispensed prescriptions with a diagnosis of GAD (ICD-10 diagnosis code F41.1) between 10/1/2003 and 9/30/2004 ("GAD patients"). Among GAD-related medications (including benzodiazepines, tricyclic antidepressants [TCAs], selective serotonin reuptake inhibitors, venlafaxine, hydroxyzine, buspirone, pregabalin, and trifluoperazine), long-acting benzodiazepines, selected short-acting benzodiazepines at relatively high dosages, selected TCAs, and hydroxyzine were designated "potentially inappropriate" for use in patients aged ≥ 65 years, based on published criteria.</p> <p>Results</p> <p>A total of 975 elderly patients with GAD were identified. Mean age was 75 years, and 72% were women; 29% had diagnoses of comorbid depression. Forty percent of study subjects received potentially inappropriate agents – most commonly, bromazepam (10% of all subjects), diazepam (9%), doxepin (7%), amitriptyline (5%), and lorazepam (5%). Twenty-three percent of study subjects received long-acting benzodiazepines, 10% received short-acting benzodiazepines at relatively high doses, and 12% received TCAs designated as potentially inappropriate.</p> <p>Conclusion</p> <p>GPs in Germany often prescribe medications that have been designated as potentially inappropriate to their elderly patients with GAD – especially those with comorbid depressive disorders. Further research is needed to ascertain whether there are specific subgoups of elderly patients with GAD for whom the benefits of these medications outweigh their risks.</p

    Potent Antioxidant and Genoprotective Effects of Boeravinone G, a Rotenoid Isolated from Boerhaavia diffusa

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    Background and Aims: Free radicals are implicated in the aetiology of some gastrointestinal disorders such as gastric ulcer, colorectal cancer and inflammatory bowel disease. In the present study we investigated the antioxidant and genoprotective activity of some rotenoids (i.e. boeravinones) isolated from the roots of Boerhaavia diffusa, a plant used in the Ayurvedic medicine for the treatment of diseases affecting the gastrointestinal tract. Methods/Principal Findings: Antioxidant activity has been evaluated using both chemical (Electron Spin Resonance spectroscopy, ESR) and Caco-2 cells-based (TBARS and ROS) assays. DNA damage was evaluated by Comet assay, while pERK 1/2 and phospho-NF-kB p65 levels were estimated by western blot. Boeravinones G, D and H significantly reduced the signal intensity of ESR induced by hydroxyl radicals, suggesting a scavenging activity. Among rotenoids tested, boeravinone G exerted the most potent effect. Boeravinone G inhibited both TBARS and ROS formation induced by Fenton's reagent, increased SOD activity and reduced H 2O 2-induced DNA damage. Finally, boeravinone G reduced the levels of pERK 1 and phospho-NF-kB p65 (but not of pERK 2) increased by Fenton's reagent. Conclusions: It is concluded that boeravinone G exhibits an extraordinary potent antioxidant activity (significant effect in the nanomolar range). The MAP kinase and NF-kB pathways seem to be involved in the antioxidant effect of boeravinone G. Boeravinone G might be considered as lead compound for the development of drugs potentially useful against those pathologies whose aetiology is related to ROS-mediated injuries

    BST2/Tetherin Enhances Entry of Human Cytomegalovirus

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    Interferon-induced BST2/Tetherin prevents budding of vpu-deficient HIV-1 by tethering mature viral particles to the plasma membrane. BST2 also inhibits release of other enveloped viruses including Ebola virus and Kaposi's sarcoma associated herpesvirus (KSHV), indicating that BST2 is a broadly acting antiviral host protein. Unexpectedly however, recovery of human cytomegalovirus (HCMV) from supernatants of BST2-expressing human fibroblasts was increased rather than decreased. Furthermore, BST2 seemed to enhance viral entry into cells since more virion proteins were released into BST2-expressing cells and subsequent viral gene expression was elevated. A significant increase in viral entry was also observed upon induction of endogenous BST2 during differentiation of the pro-monocytic cell line THP-1. Moreover, treatment of primary human monocytes with siRNA to BST2 reduced HCMV infection, suggesting that BST2 facilitates entry of HCMV into cells expressing high levels of BST2 either constitutively or in response to exogenous stimuli. Since BST2 is present in HCMV particles we propose that HCMV entry is enhanced via a reverse-tethering mechanism with BST2 in the viral envelope interacting with BST2 in the target cell membrane. Our data suggest that HCMV not only counteracts the well-established function of BST2 as inhibitor of viral egress but also employs this anti-viral protein to gain entry into BST2-expressing hematopoietic cells, a process that might play a role in hematogenous dissemination of HCMV

    Malaria Rapid Testing by Community Health Workers Is Effective and Safe for Targeting Malaria Treatment: Randomised Cross-Over Trial in Tanzania

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    Early diagnosis and prompt, effective treatment of uncomplicated malaria is critical to prevent severe disease, death and malaria transmission. We assessed the impact of rapid malaria diagnostic tests (RDTs) by community health workers (CHWs) on provision of artemisinin-based combination therapy (ACT) and health outcome in fever patients. Twenty-two CHWs from five villages in Kibaha District, a high-malaria transmission area in Coast Region, Tanzania, were trained to manage uncomplicated malaria using RDT aided diagnosis or clinical diagnosis (CD) only. Each CHW was randomly assigned to use either RDT or CD the first week and thereafter alternating weekly. Primary outcome was provision of ACT and main secondary outcomes were referral rates and health status by days 3 and 7. The CHWs enrolled 2930 fever patients during five months of whom 1988 (67.8%) presented within 24 hours of fever onset. ACT was provided to 775 of 1457 (53.2%) patients during RDT weeks and to 1422 of 1473 (96.5%) patients during CD weeks (Odds Ratio (OR) 0.039, 95% CI 0.029-0.053). The CHWs adhered to the RDT results in 1411 of 1457 (96.8%, 95% CI 95.8-97.6) patients. More patients were referred on inclusion day during RDT weeks (10.0%) compared to CD weeks (1.6%). Referral during days 1-7 and perceived non-recovery on days 3 and 7 were also more common after RDT aided diagnosis. However, no fatal or severe malaria occurred among 682 patients in the RDT group who were not treated with ACT, supporting the safety of withholding ACT to RDT negative patients. RDTs in the hands of CHWs may safely improve early and well-targeted ACT treatment in malaria patients at community level in Africa.\ud \ud \ud \u

    Participant experiences of mindfulness-based childbirth education: a qualitative study

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    Background: Childbirth is an important transitional life event, but one in which many women are dissatisfied stemming in part from a sense that labour is something that happens to them rather than with them. Promoting maternal satisfaction with childbirth means equipping women with communication and decision making skills that will enhance their ability to feel involved in their labour. Additionally, traditional antenatal education does not necessarily prepare expectant mothers and their birth support partner adequately for birth. Mindfulness-based interventions appear to hold promise in addressing these issues. Mindfulness-based Child Birth Education (MBCE) was a pilot intervention combining skills-based antenatal education and Mindfulness Based Stress Reduction. Participant experiences of MBCE, both of expectant mothers and their birth support partners are the focus of this article. Methods: A generic qualitative approach was utilised for this study. Pregnant women between 18 and 28 weeks gestation, over 18 years of age, nulliparous with singleton pregnancies and not taking medication for a diagnosed mental illness or taking illicit drugs were eligible to undertake the MBCE program which was run in a metropolitan city in Australia. Focus groups with 12 mothers and seven birth support partners were undertaken approximately four months after the completion of MBCE. Audio recordings of the groups were transcribed verbatim and analysed thematically using the method of constant comparison by all four authors independently and consensus on analysis and interpretation arrived at through team meetings.Results: A sense of both ‘empowerment’ and ‘community’ were the essences of the experiences of MBCE both for mothers and their birth support partner and permeated the themes of ‘awakening my existing potential’ and ‘being in a community of like-minded parents’. Participants suggested that mindfulness techniques learned during MBCE facilitated their sense of control during birth, and the content and pedagogical approach of MBCE enabled them to be involved in decision making during the birth. The pedagogical approach also fostered a sense of community among participants which extended into the postnatal period. Conclusions: MBCE has the potential to empower women to become active participants in the birthing process, thus addressing common concerns regarding lack of control and satisfaction with labour and facilitate peer support into the postnatal period. Further education of health professionals may be needed to ensure that they respond positively to those women and birth support partners who remain active in decision making during birth

    Predicting Peptide Binding Affinities to MHC Molecules Using a Modified Semi-Empirical Scoring Function

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    The Major Histocompatibility Complex (MHC) plays an important role in the human immune system. The MHC is involved in the antigen presentation system assisting T cells to identify foreign or pathogenic proteins. However, an MHC molecule binding a self-peptide may incorrectly trigger an immune response and cause an autoimmune disease, such as multiple sclerosis. Understanding the molecular mechanism of this process will greatly assist in determining the aetiology of various diseases and in the design of effective drugs. In the present study, we have used the Fresno semi-empirical scoring function and modify the approach to the prediction of peptide-MHC binding by using open-source and public domain software. We apply the method to HLA class II alleles DR15, DR1, and DR4, and the HLA class I allele HLA A2. Our analysis shows that using a large set of binding data and multiple crystal structures improves the predictive capability of the method. The performance of the method is also shown to be correlated to the structural similarity of the crystal structures used. We have exposed some of the obstacles faced by structure-based prediction methods and proposed possible solutions to those obstacles. It is envisaged that these obstacles need to be addressed before the performance of structure-based methods can be on par with the sequence-based methods

    Prevalence of inappropriate medication using Beers criteria in Japanese long-term care facilities

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    BACKGROUND: The prevalence and risk factors of potentially inappropriate medication use among the elderly patients have been studied in various countries, but because of the difficulty of obtaining data on patient characteristics and medications they have not been studied in Japan. METHODS: We conducted a retrospective cross-sectional study in 17 Japanese long-term care (LTC) facilities by collecting data from the comprehensive MDS assessment forms for 1669 patients aged 65 years and over who were assessed between January and July of 2002. Potentially inappropriate medications were identified on the basis of the 2003 Beers criteria. RESULTS: The patients in the sample were similar in terms of demographic characteristics to those in the national survey. Our study revealed that 356 (21.1%) of the patients were treated with potentially inappropriate medication independent of disease or condition. The most commonly inappropriately prescribed medication was ticlopidine, which had been prescribed for 107 patients (6.3%). There were 300 (18.0%) patients treated with at least 1 inappropriate medication dependent on the disease or condition. The highest prevalence of inappropriate medication use dependent on the disease or condition was found in patients with chronic constipation. Multiple logistic regression analysis revealed psychotropic drug use (OR = 1.511), medication cost of per day (OR = 1.173), number of medications (OR = 1.140), and age (OR = 0.981) as factors related to inappropriate medication use independent of disease or condition. Neither patient characteristics nor facility characteristics emerged as predictors of inappropriate prescription. CONCLUSION: The prevalence and predictors of inappropriate medication use in Japanese LTC facilities were similar to those in other countries
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