Two-pronged attack: dual inhibition of Plasmodium falciparum M1 and M17 metalloaminopeptidases by a novel series of hydroxamic acid-based inhibitors

Plasmodium parasites, the causative agents of malaria, have developed resistance to most of our current antimalarial therapies, including artemisinin combination therapies which are widely described as our last line of defense. Antimalarial agents with a novel mode of action are urgently required. Two Plasmodium falciparum aminopeptidases, PfA-M1 and PfA-M17, play crucial roles in the erythrocytic stage of infection and have been validated as potential antimalarial targets. Using compound-bound crystal structures of both enzymes, we have used a structure-guided approach to develop a novel series of inhibitors capable of potent inhibition of both PfA-M1 and PfA-M17 activity and parasite growth in culture. Herein we describe the design, synthesis, and evaluation of a series of hydroxamic acid-based inhibitors and demonstrate the compounds to be exciting new leads for the development of novel antimalarial therapeutics

Mobilizing older adults: A multi-site, exploratory and observational study on patients enrolled in the Hospital Elder Life Program (HELP).

The aim of this study was to explore and describe the characteristics of the Hospital Elder Life Program (HELP) sites and how they mobilize patients with volunteers in the United States and other countries. The purpose was to describe: the number of enrollments, modalities, fall and injury rates, and to identify barriers to mobilization. A survey was distributed to 228 international sites. The responding sites enrolled an average of 53.9 (SD 35.3) patients per month. The majority (76%) reported that mobilization included \u27active range of motion exercises\u27 and \u27ambulation\u27. Eighteen percent identified volunteer training, safety and liability concerns as barriers. Falls with injury on HELP units was 0-3%, with an average rate of 0.46 per 1,000 patient days. No patient falls while ambulating with the HELP team and/or volunteers were reported. More research and evidence are needed to further determine barriers and safety of mobilization with the HELP during hospitalization

Mobilizing older adults: A multi-site, exploratory and observational study on patients enrolled in the Hospital Elder Life Program (HELP).

The aim of this study was to explore and describe the characteristics of the Hospital Elder Life Program (HELP) sites and how they mobilize patients with volunteers in the United States and other countries. The purpose was to describe: the number of enrollments, modalities, fall and injury rates, and to identify barriers to mobilization. A survey was distributed to 228 international sites. The responding sites enrolled an average of 53.9 (SD 35.3) patients per month. The majority (76%) reported that mobilization included \u27active range of motion exercises\u27 and \u27ambulation\u27. Eighteen percent identified volunteer training, safety and liability concerns as barriers. Falls with injury on HELP units was 0–3%, with an average rate of 0.46 per 1,000 patient days. No patient falls while ambulating with the HELP team and/or volunteers were reported. More research and evidence are needed to further determine barriers and safety of mobilization with the HELP during hospitalization

Falls and delirium in an acute care setting: A retrospective chart review before and after an organisation‐wide interprofessional education.

p \u3c .001). The confusion assessment method (CAM) identified the diagnosis of delirium at 76% accuracy. The length of stay decreased by 7.3 days. The fall rates in 2011 and 2012 were 3.01 and 2.82 falls per 1,000 patient days and in 2013 decreased to 2.16. Conclusion: The results indicate that improving delirium recognition and treatment through interprofessional education can reduce falls and length of stay. Relevance to clinical practice: The results demonstrate that when staff learn to prevent, identify, manage and document delirium more accurately the fall rate decreases. The practice change, including the use of CAM, was sustained by continuous auditing including re‐education, and the re‐enforcement of learning along with the implementation of a policy. } data-sheets-userformat= { 2 :33569153, 3 :{ 1 :0, 3 :1}, 10 :0, 11 :4, 14 :[null,2,0], 15 : Calibri , 16 :11, 28 :1} \u3eAim and objectives: To describe and compare identification of delirium, length of stay and discharge locations in two patient samples of falls, before and after an organisation‐wide interprofessional delirium education and practice change along with implementation of a policy. Background: Delirium is a common and severe problem for hospitalised patients, with occurrence ranging from 14%–56%, morbidity and mortality from 25%–33%. Recent studies report that 73%–96% of patients who fell during a hospital stay had symptoms of delirium; however, the delirium went undiagnosed and untreated in 75% of the cases. Design: A descriptive, retrospective observational study using a pre/postdesign. Methods: Two chart reviews were performed on patient falls as identified in the hospital safety reporting system in 2009–2010 (98 fallers) and 2012 (108 fallers). An organisation‐wide education was planned and implemented with monitoring of policy compliance. Results: After the education, documentation of the “diagnosis of delirium” and “no evidence of delirium” increased from 14.3%–29.5% and from 27.6%–44.4%. The documentation of “evidence of delirium” decreased significantly from 58.2%–25.9% (p \u3c .001). The confusion assessment method (CAM) identified the diagnosis of delirium at 76% accuracy. The length of stay decreased by 7.3 days. The fall rates in 2011 and 2012 were 3.01 and 2.82 falls per 1,000 patient days and in 2013 decreased to 2.16. Conclusion: The results indicate that improving delirium recognition and treatment through interprofessional education can reduce falls and length of stay. Relevance to clinical practice: The results demonstrate that when staff learn to prevent, identify, manage and document delirium more accurately the fall rate decreases. The practice change, including the use of CAM, was sustained by continuous auditing including re‐education, and the re‐enforcement of learning along with the implementation of a policy

Falls and delirium in an acute care setting: A retrospective chart review before and after an organisation-wide interprofessional education.

AIM AND OBJECTIVES: To describe and compare identification of delirium, length of stay and discharge locations in two patient samples of falls, before and after an organisation-wide interprofessional delirium education and practice change along with implementation of a policy. BACKGROUND: Delirium is a common and severe problem for hospitalised patients, with occurrence ranging from 14%-56%, morbidity and mortality from 25%-33%. Recent studies report that 73%-96% of patients who fell during a hospital stay had symptoms of delirium; however, the delirium went undiagnosed and untreated in 75% of the cases. DESIGN: A descriptive, retrospective observational study using a pre/postdesign. METHODS: Two chart reviews were performed on patient falls as identified in the hospital safety reporting system in 2009-2010 (98 fallers) and 2012 (108 fallers). An organisation-wide education was planned and implemented with monitoring of policy compliance. RESULTS: After the education, documentation of the diagnosis of delirium and no evidence of delirium increased from 14.3%-29.5% and from 27.6%-44.4%. The documentation of evidence of delirium decreased significantly from 58.2%-25.9% (p \u3c .001). The confusion assessment method (CAM) identified the diagnosis of delirium at 76% accuracy. The length of stay decreased by 7.3 days. The fall rates in 2011 and 2012 were 3.01 and 2.82 falls per 1,000 patient days and in 2013 decreased to 2.16. CONCLUSION: The results indicate that improving delirium recognition and treatment through interprofessional education can reduce falls and length of stay. RELEVANCE TO CLINICAL PRACTICE: The results demonstrate that when staff learn to prevent, identify, manage and document delirium more accurately the fall rate decreases. The practice change, including the use of CAM, was sustained by continuous auditing including re-education, and the re-enforcement of learning along with the implementation of a policy

Falls in A Tertiary Care Hospital-Association With Delirium: A Replication Study.

BACKGROUND: Delirium has been previously implicated as a risk factor for patient falls. This is a replication study of a 2009 investigation examining the prevalence of diagnosed and undiagnosed delirium in patients who fell during their hospital stay. OBJECTIVE: To determine the prevalence of delirium at our institution and to examine the relationship of falls with delirium, advanced age, and hospital procedures. METHOD: Using the data collection tool developed for the 2009 study, the authors performed a retrospective review of records of 99 patients who fell during their inpatient stay. Similar information was gathered on patient demographics, fall date, fall location, hospital service type, discharge disposition, diagnosis of delirium (DD), synonyms used to describe delirium, metabolic derangements, and surgeries or procedures performed. Data were collected on the day of admission, day of the fall, and 2 days before the fall. RESULTS: Falls in the general hospital were associated with delirium (73% of subjects had evidence or a DD at the time of their fall), advanced age (64.5% were older than 70 years), and specific procedures and surgeries. CONCLUSION: As identified in the previous study, improving delirium recognition and treatment may reduce the number of patient falls and promote more favorable outcomes such as reduced length of stay, fewer discharges to intermediate care facilities, and prevention of fall injuries. A comprehensive fall risk assessment that includes a delirium detection tool would improve the sensitivity and specificity of these instruments to detect those at greatest risk