Projects & Collaborations 3 foundShow per page10 10 20 50 Targeted correction of plasma sodium levels in hospitalized patients with hyponatremia: a randomized, controlled, parallel-group trial with blinded outcome-assessment - The Hyponatremia Intervention Trial (HIT trial) Research Project | 6 Project MembersHyponatremia is the most common electrolyte disorder with a prevalence of up to 30% in hospitalized patients. It can be caused by the underlying disease, prescribed drugs, or aspecific stimuli such as nausea and pain. Hyponatremia may be life-threatening if it develops acutely and causes cerebral edema with neurological symptoms. The treatment of acute symptomatic hyponatremia is therefore straight forward and implies the administration of hypertonic saline to treat cerebral edema. In contrast, the rationale for treatment of chronic hyponatremia - the most prevalent subtype - is less evident. There are no intervention studies to show that correcting chronic hyponatremia improves outcomes.Importantly, there is increasing data showing an association between chronic hyponatremia and complications such as falls or attention deficit, as well as increased risk of fractures and osteoporosis. It has also been reported that hyponatremia is associated with a poorer prognosis of cardiac, hepatic, kidney and pulmonary diseases as well as the overall outcome of ICU patients resulting in a significant association with an increased mortality and readmission risk. However, it is unclear whether these are merely associations or indicate causality: despite several retrospective analyses showing improvement of readmission and mortality rates, as well as some small uncontrolled studies reporting reduction of adverse events with plasma sodium correction, there is a complete lack of randomized clinical trials investigating whether correction of hyponatremia counteracts the increased risk of readmission and mortality. Thus, there is clinical equipoise on whether chronic hyponatremia should be treated or not. Therefore, the aim of this intervention study is to determine the benefits and harms of a targeted correction of plasma sodium concentration on the combined endpoint 30-day mortality and rehospitalization rate. Patients will be randomly assigned to targeted correction of plasma sodium concentration or standard care alone. Study Design: Pragmatic randomized (1:1 ratio) controlled, superiority, parallel-group international multi-center study with blinded outcome assessment.Patients: Hospitalized patients with chronic hypotonic hyponatremia <130mmol/l. Patients requiring acute treatment with 3% saline infusion due to severe symptomatic hyponatremia, patients on dialysis, patients with acute liver failure, encephalopathic complications of liver failure or hepatorenal syndrome will be excluded. Intervention: Targeted correction of plasma sodium concentrationComparison: Current standard careOutcome measures: The primary objective is to investigate whether targeted correction of hyponatremia compared to standard care alone reduces the combined risk of death or rehospitalization within 30 days. Secondary objectives will include: Short- (30 days) and longterm (1 year) risk of death and rehospitalization; other clinical outcomes (neurocognition, quality of life, falls, fractures, length of hospital stay); Safety of the intervention; Exploratory analysis of biomarkers for hyponatremia. Main statistical hypothesis and sample size calculation:The intervention is superior to standard care by reducing the patients risk of death or re-hospitalization within 30 days from 23% to 18%. 2050 patients are required to detect an effect that is relevant for patients, clinicians and policy makers, i.e. an absolute reduction of 5% of the primary outcome (combined mortality and rehospitalization rate) with a statistical power of 80% (two-sided significance level 5%). With an assumed drop-out rate of 10 %, 2278 patients should be recruited.Importance: This study will influence future hyponatremia management on a national and international level regardless of its outcome:If the intervention results in a significant reduction of mortality and rehospitalization rate, hyponatremia awareness and its consecutive treatment during hospitalization will change substantially.If the intervention shows no effect on mortality and rehospitalization rate, hyponatremia will be recognized more as a marker of severity of the disease and not as its cause. Current treatment guidelines will be adapted. Calcitonin Gene derived peptides for an Optimized Patient Transfer using an Innovative Multidisciplinary Assessment in the Canton Aargau (OPTIMA II) Research Project | 1 Project MembersCommunity-acquired lower respiratory tract infections (LRTIs) include acute bronchitis, acute exacerbations of chronic obstructive pulmonary disease and pneumonia (CAP). They are among the most frequent causes of hospitalization1 and direct treatment costs amount to $15 billion in the USA2. Inpatient care of CAP is 8 to 20 times more expensive 3, 4 and carries a higher risk of nosocomial infections including Clostridium difficile-associated diarrhea5 than outpatient treatment. Many patients prefer outpatient treatment6. Nevertheless, despite a low-risk according to clinical severity scores, many patients are hospitalized for medical comorbidities and psychosocial reasons4, 7. Admission rates and length of stay are affected by a variety of medical, functional, psychosocial factors including patient and relatives preferences4, 7-9. In our multicentre ProHOSP study, compliance with the procalcitonin (PCT)-guided antibiotic algorithm was 90%10. Importantly, only half of the patients in the low medical risk groups as determined by PSI are treated as outpatients despite high intensity implementation10, 11. Regardless of low observed risk for adverse events, fear of medical complications was the dominant motive for hospitalization similarly among physicians, nurses, patients and relatives 12. This malcompliance may be due among others to the static behavior of the CAP severity scores during the course of the disease, the considerable variability in outcome within a given risk category and poor memorizability13. Intervention bundles reduce hospitalization rate and length of stay particularly in low-risk patients, and decrease antibiotic use and overall costs while achieving similar quality of life and patient outcomes in CAP14, 15. To assess nursing-related risk of patients, functional and frailty scores of varying complexity were developed. The ?Selbstpflegeindex? (SPI=self care index) is a simple and commonly used nursing and geriatric tool to assess functional dependence in activities of daily life. A score of <32 points indicates a risk for post-acute care deficit16. As a 5-variable scoring system the post-acute care discharge score (PACD) facilitates discharge planning17. A ?8 point score on day 3 of hospitalization was accurate (AUC: 0.82) to predict discharge to a post-acute care facility. Similarly, 5 items were independently associated with discharge to post-acute care if assessed on day 1 of admission. Nurse led units (NLU) are defined as institutional settings, typically within acute care hospitals, which provide independent specialized nursing service for post-acute care patients, who need predominantly nursing care. They constitute a possible model of care for patients with low medical yet high nursing risk18, 19 and are characterized and operationalized by five factors: 1) In-patient environment offering active treatment; 2) case mix based on nursing needs; 3) nursing leadership of the (multidisciplinary) clinical team; 4) nursing conceptualized as the predominant active therapy; 5) nurses? authority to admit and discharge patients18, 19. There are indications that post-acute care patients cared for in NLUs have a better functional status and a greater psychological well-being at discharge, are more often discharged home than to another institution and are less often readmitted early to the hospital than patients receiving usual care. There are also indications that these patients are more satisfied with the provided service19-21. Biomarkers are objective, dynamic, easily measurable and lack the need for memorizing complex algorithms. PCT-guided antibiotic therapy was shown in 11 randomized controlled trials (5 performed by our group)10, 22-25 to safely reduce antibiotic exposure in LRTIs by up to 75%26-28 and has been successfully implemented into clinical routine29. Unfortunately, CRP, PCT or other routinely measured markers have at best a moderate prognostic utility in LRTI 30-33. REGULATION, FUNCTION AND PLASTICITY OF CALCITONIN PEPTIDES AND OTHER “HORMOKINES” DURING INFLAMMATION AND INFECTION Research Project | 1 Project MembersRegulation, function and plasticity of c 1 1
Targeted correction of plasma sodium levels in hospitalized patients with hyponatremia: a randomized, controlled, parallel-group trial with blinded outcome-assessment - The Hyponatremia Intervention Trial (HIT trial) Research Project | 6 Project MembersHyponatremia is the most common electrolyte disorder with a prevalence of up to 30% in hospitalized patients. It can be caused by the underlying disease, prescribed drugs, or aspecific stimuli such as nausea and pain. Hyponatremia may be life-threatening if it develops acutely and causes cerebral edema with neurological symptoms. The treatment of acute symptomatic hyponatremia is therefore straight forward and implies the administration of hypertonic saline to treat cerebral edema. In contrast, the rationale for treatment of chronic hyponatremia - the most prevalent subtype - is less evident. There are no intervention studies to show that correcting chronic hyponatremia improves outcomes.Importantly, there is increasing data showing an association between chronic hyponatremia and complications such as falls or attention deficit, as well as increased risk of fractures and osteoporosis. It has also been reported that hyponatremia is associated with a poorer prognosis of cardiac, hepatic, kidney and pulmonary diseases as well as the overall outcome of ICU patients resulting in a significant association with an increased mortality and readmission risk. However, it is unclear whether these are merely associations or indicate causality: despite several retrospective analyses showing improvement of readmission and mortality rates, as well as some small uncontrolled studies reporting reduction of adverse events with plasma sodium correction, there is a complete lack of randomized clinical trials investigating whether correction of hyponatremia counteracts the increased risk of readmission and mortality. Thus, there is clinical equipoise on whether chronic hyponatremia should be treated or not. Therefore, the aim of this intervention study is to determine the benefits and harms of a targeted correction of plasma sodium concentration on the combined endpoint 30-day mortality and rehospitalization rate. Patients will be randomly assigned to targeted correction of plasma sodium concentration or standard care alone. Study Design: Pragmatic randomized (1:1 ratio) controlled, superiority, parallel-group international multi-center study with blinded outcome assessment.Patients: Hospitalized patients with chronic hypotonic hyponatremia <130mmol/l. Patients requiring acute treatment with 3% saline infusion due to severe symptomatic hyponatremia, patients on dialysis, patients with acute liver failure, encephalopathic complications of liver failure or hepatorenal syndrome will be excluded. Intervention: Targeted correction of plasma sodium concentrationComparison: Current standard careOutcome measures: The primary objective is to investigate whether targeted correction of hyponatremia compared to standard care alone reduces the combined risk of death or rehospitalization within 30 days. Secondary objectives will include: Short- (30 days) and longterm (1 year) risk of death and rehospitalization; other clinical outcomes (neurocognition, quality of life, falls, fractures, length of hospital stay); Safety of the intervention; Exploratory analysis of biomarkers for hyponatremia. Main statistical hypothesis and sample size calculation:The intervention is superior to standard care by reducing the patients risk of death or re-hospitalization within 30 days from 23% to 18%. 2050 patients are required to detect an effect that is relevant for patients, clinicians and policy makers, i.e. an absolute reduction of 5% of the primary outcome (combined mortality and rehospitalization rate) with a statistical power of 80% (two-sided significance level 5%). With an assumed drop-out rate of 10 %, 2278 patients should be recruited.Importance: This study will influence future hyponatremia management on a national and international level regardless of its outcome:If the intervention results in a significant reduction of mortality and rehospitalization rate, hyponatremia awareness and its consecutive treatment during hospitalization will change substantially.If the intervention shows no effect on mortality and rehospitalization rate, hyponatremia will be recognized more as a marker of severity of the disease and not as its cause. Current treatment guidelines will be adapted.
Calcitonin Gene derived peptides for an Optimized Patient Transfer using an Innovative Multidisciplinary Assessment in the Canton Aargau (OPTIMA II) Research Project | 1 Project MembersCommunity-acquired lower respiratory tract infections (LRTIs) include acute bronchitis, acute exacerbations of chronic obstructive pulmonary disease and pneumonia (CAP). They are among the most frequent causes of hospitalization1 and direct treatment costs amount to $15 billion in the USA2. Inpatient care of CAP is 8 to 20 times more expensive 3, 4 and carries a higher risk of nosocomial infections including Clostridium difficile-associated diarrhea5 than outpatient treatment. Many patients prefer outpatient treatment6. Nevertheless, despite a low-risk according to clinical severity scores, many patients are hospitalized for medical comorbidities and psychosocial reasons4, 7. Admission rates and length of stay are affected by a variety of medical, functional, psychosocial factors including patient and relatives preferences4, 7-9. In our multicentre ProHOSP study, compliance with the procalcitonin (PCT)-guided antibiotic algorithm was 90%10. Importantly, only half of the patients in the low medical risk groups as determined by PSI are treated as outpatients despite high intensity implementation10, 11. Regardless of low observed risk for adverse events, fear of medical complications was the dominant motive for hospitalization similarly among physicians, nurses, patients and relatives 12. This malcompliance may be due among others to the static behavior of the CAP severity scores during the course of the disease, the considerable variability in outcome within a given risk category and poor memorizability13. Intervention bundles reduce hospitalization rate and length of stay particularly in low-risk patients, and decrease antibiotic use and overall costs while achieving similar quality of life and patient outcomes in CAP14, 15. To assess nursing-related risk of patients, functional and frailty scores of varying complexity were developed. The ?Selbstpflegeindex? (SPI=self care index) is a simple and commonly used nursing and geriatric tool to assess functional dependence in activities of daily life. A score of <32 points indicates a risk for post-acute care deficit16. As a 5-variable scoring system the post-acute care discharge score (PACD) facilitates discharge planning17. A ?8 point score on day 3 of hospitalization was accurate (AUC: 0.82) to predict discharge to a post-acute care facility. Similarly, 5 items were independently associated with discharge to post-acute care if assessed on day 1 of admission. Nurse led units (NLU) are defined as institutional settings, typically within acute care hospitals, which provide independent specialized nursing service for post-acute care patients, who need predominantly nursing care. They constitute a possible model of care for patients with low medical yet high nursing risk18, 19 and are characterized and operationalized by five factors: 1) In-patient environment offering active treatment; 2) case mix based on nursing needs; 3) nursing leadership of the (multidisciplinary) clinical team; 4) nursing conceptualized as the predominant active therapy; 5) nurses? authority to admit and discharge patients18, 19. There are indications that post-acute care patients cared for in NLUs have a better functional status and a greater psychological well-being at discharge, are more often discharged home than to another institution and are less often readmitted early to the hospital than patients receiving usual care. There are also indications that these patients are more satisfied with the provided service19-21. Biomarkers are objective, dynamic, easily measurable and lack the need for memorizing complex algorithms. PCT-guided antibiotic therapy was shown in 11 randomized controlled trials (5 performed by our group)10, 22-25 to safely reduce antibiotic exposure in LRTIs by up to 75%26-28 and has been successfully implemented into clinical routine29. Unfortunately, CRP, PCT or other routinely measured markers have at best a moderate prognostic utility in LRTI 30-33.
REGULATION, FUNCTION AND PLASTICITY OF CALCITONIN PEPTIDES AND OTHER “HORMOKINES” DURING INFLAMMATION AND INFECTION Research Project | 1 Project MembersRegulation, function and plasticity of c
