Christian Klem - Academia.edu (original) (raw)
Papers by Christian Klem
PubMed, Aug 1, 1996
Pharmacists have an integral role in the care of ICU patients, including those with infections. A... more Pharmacists have an integral role in the care of ICU patients, including those with infections. Antibiotics continue to be among the most widely prescribed drugs in the ICU environment. This article focuses on the impact pharmacists have on the care and economics for the critically ill infected patient and on mechanisms used in hospitals to control antibiotic misuse. Numerous studies point to inappropriate antibiotic use and resultant selection pressure on antimicrobial resistance. The critical care pharmacist can impact this prescribing by assuring optimal pharmacotherapy specific for the organism and associated disease. Furthermore, policies have been implemented to modify antibiotic use, including formulary manipulations, antibiotic stop order forms, care plans, antibiotic cycling, oral switching, and computer-assisted antimicrobial therapy. Future research is needed to determine the optimal method for preventing resistance. However, a multidisciplinary approach to rational antimicrobial use is suggested.
PubMed, Jul 5, 2011
Objectives: Current aim of rheumatoid arthritis (RA) treatment is to achieve remission in as many... more Objectives: Current aim of rheumatoid arthritis (RA) treatment is to achieve remission in as many patients as possible. Rates of remission and clinical outcomes after treatment with abatacept in biologic-naive rheumatoid arthritis (RA) patients with early disease and an inadequate response to methotrexate (MTX) versus patients with ≥ 10 years of disease were assessed. Methods: Data from two trials assessing the efficacy of abatacept in MTX inadequate responders were pooled for this exploratory post hoc analysis. Patients with disease duration of ≤ 2 years at baseline (early disease), originally assigned to an abatacept approximately 10 mg/kg treatment arm and entered into a long-term extension (LTE), were compared with patients with ≥ 10 years of disease (long-standing RA). Remission, DAS28-CRP, ACR 70 responses and the Routine Assessment of Patient Index Data 3 (RAPID3), improvement in physical function as measured by the Health Assessment Questionnaire Disability Index (HAQ-DI). Results: Twenty-three percent of these patients (n=108) had early disease. A higher percentage of patients with early disease achieved DAS28-CRP remission versus patients with long-standing disease (35.2% vs. 19.4% at year 1, p<0.01; 46.0% vs. 30.9% at year 3, p<0.05). In addition, a higher percentage of the subgroup with early RA achieved ACR70 responses. More patients with early RA had a meaningful improvement in their HAQ-DI (75.2% vs. 60.4%; p<0.05) and RAPID3 scores at one year (mean changes from baseline of -9.6 vs. -8.1; p=0.009). Conclusions: These data provide additional support for the possible use of abatacept in biologic-naive patients who have had inadequate response to MTX, earlier in their disease course.
Clinical and Applied Thrombosis/Hemostasis
IMPORTANCE Many patients with nonvalvular atrial fibrillation (NVAF) are at a high risk of gastro... more IMPORTANCE Many patients with nonvalvular atrial fibrillation (NVAF) are at a high risk of gastrointestinal (GI) bleeding due to conditions including older age; stage III to V chronic kidney disease (CKD); HAS-BLED (hypertension, kidney or liver disease, stroke history, prior bleeding, unstable international normalized ratio, age >65, drug or alcohol use) score of 3 or greater; corticosteroid, antiplatelet or nonsteroidal anti-inflammatory drug (NSAID) use; or GI conditions. OBJECTIVE To compare the risk of stroke and/or systemic embolism (SE) and major bleeding (MB) among patients with NVAF and high risk of GI bleeding who received non-vitamin K antagonist oral anticoagulants (NOACs) vs those who received warfarin.
BMJ, 2016
Medical Publishing Insights & Practices (MPIP)-a partnership among pharmaceutical companies and t... more Medical Publishing Insights & Practices (MPIP)-a partnership among pharmaceutical companies and the International Society for Medical Publication Professionals-aims to identify ways to improve transparency and credibility in publishing the results of industry sponsored research. This article provides guidance from MPIP on clinically relevant and more informative adverse event reporting, previously identified by journal editors as a significant unmet need to improve patient care and increase the credibility of industry sponsored publications. Our recommendations include highlighting adverse events of most relevance to practitioners and their patients, avoiding broad summary statements such as "generally safe" or "well tolerated," and including more detailed adverse event data (where appropriate) to offer additional clinically important insight. These recommendations complement the earlier recommendations in the Consolidated Standards of Reporting Trials (CONSORT) Harms Extension. Although developed for industry sponsored trials, the adoption of our recommendations would enhance adverse event reporting in clinical research publications regardless of the funding source and thereby facilitate clinical decision making. Summary pointS Objective reporting of adverse event data within clinical trials publications could provide greater context and clarity for the application of trial results to daily clinical practice Conference and manuscript abstracts should include objective information on the incidence and type of clinically relevant adverse events instead of overly general statements such as "well tolerated" Clinically relevant adverse events should be identified and communicated with clarity around relevant clinical characteristics, such as severity, frequency, and timing, which could be more informative than incidence rates Adverse event reporting should include numerators and denominators for all events; formal statistical analyses should be used selectively, and post hoc analyses should be clearly identified
Advances in Therapy
Introduction: Non-valvular atrial fibrillation (NVAF) is often accompanied by multiple comorbid c... more Introduction: Non-valvular atrial fibrillation (NVAF) is often accompanied by multiple comorbid conditions, which increase the associated risks and complexity of patient management. This study evaluated the risk of stroke/systemic embolism (SE) and major bleeding (MB) among multimorbid patients with NVAF who were prescribed non-vitamin K antagonist oral anticoagulants (NOACs) or warfarin. Methods: A retrospective study of patients with NVAF and high multimorbidity who initiated apixaban, dabigatran, rivaroxaban, or warfarin from 1 January 2013 to 30 September 2015 was conducted using five insurance claims databases. Multimorbidity was defined as six or more comorbid conditions, and 1:1 propensity score matching (PSM) was conducted between the NOAC-warfarin and NOAC-NOAC cohorts. Cox proportional hazard models were used to evaluate the hazard ratios of stroke/SE and MB.
The Canadian Journal of Hospital Pharmacy, 2018
European Heart Journal - Cardiovascular Pharmacotherapy
Aims Polypharmacy is prevalent among non-valvular atrial fibrillation (NVAF) patients and present... more Aims Polypharmacy is prevalent among non-valvular atrial fibrillation (NVAF) patients and presents a potential issue for the effective management of NVAF. This study compared the risk of stroke/systemic embolism (SE) and major bleeding (MB) among NVAF patients with polypharmacy newly prescribed oral anticoagulants (OACs). Methods and results A retrospective study of NVAF patients with polypharmacy who initiated OACs from 01 January 2013 to 30 September 2015 was conducted using US CMS Medicare and four commercial databases. Polypharmacy was defined as ≥6 concomitant medications on the index date. Propensity score matching was conducted to compare non-vitamin K antagonists OACs (NOACs) to warfarin as well as between NOACs. Cox proportional hazard models were used to evaluate the risk of stroke/SE and MB. A total of 188 893 patients with polypharmacy were included, with an average of 8 concomitant medications (interquartile range 6–9). Compared to warfarin, apixaban [hazard ratio (HR):...
JAMA Network Open
IMPORTANCE Many patients with nonvalvular atrial fibrillation (NVAF) are at a high risk of gastro... more IMPORTANCE Many patients with nonvalvular atrial fibrillation (NVAF) are at a high risk of gastrointestinal (GI) bleeding due to conditions including older age; stage III to V chronic kidney disease (CKD); HAS-BLED (hypertension, kidney or liver disease, stroke history, prior bleeding, unstable international normalized ratio, age >65, drug or alcohol use) score of 3 or greater; corticosteroid, antiplatelet or nonsteroidal anti-inflammatory drug (NSAID) use; or GI conditions. OBJECTIVE To compare the risk of stroke and/or systemic embolism (SE) and major bleeding (MB) among patients with NVAF and high risk of GI bleeding who received non-vitamin K antagonist oral anticoagulants (NOACs) vs those who received warfarin.
Critical Care Medicine, 1994
Critical Care Medicine, 2000
Objective. To identify and describe the scope of practice that characterizes the critical care ph... more Objective. To identify and describe the scope of practice that characterizes the critical care pharmacist and critical care pharmacy services. Specifically, the goals were to define the level of clinical practice and specialized skills characterizing the critical care pharmacist as clinician, educator, researcher, and manager; and to recommend fundamental, desirable, and optimal pharmacy services and personnel requirements for the provision of pharmaceutical care to critically ill patients. Hospitals having comprehensive resources as well as those with more limited resources were considered. Data Sources. Consensus of critical care pharmacists from institutions of various sizes providing critical care services within several types of pharmacy practice models was obtained, including community-based and academic practice settings. Existing guidelines and literature describing pharmacy practice and drug use processes were reviewed and adapted for the critical care setting. Conclusions. By combining the strengths and expertise of critical care pharmacy specialists with existing supporting literature, these recommendations define the level of clinical practice and specialized skills that characterize the critical care pharmacist as clinician, educator, researcher, and administrator. This position paper recommends fundamental, desirable, and optimal pharmacy services as well as personnel requirements for the provision of pharmaceutical care to critically ill patients.
Critical Care Medicine, 1994
To delineate the variability in the pharmacokinetics of dobutamine over time in an unstable criti... more To delineate the variability in the pharmacokinetics of dobutamine over time in an unstable critically ill adult surgical patient population concurrently receiving therapeutic interventions to optimize oxygen delivery and consumption variables. Prospective study. University hospital adult surgical intensive care unit. Sixteen hemodynamically unstable adults (aged 18 to 84 yrs) requiring dobutamine for inotropic support. None. Samples for dobutamine serum concentration determination were collected at selected times during therapy, following at least 30 mins of a constant infusion rate and measured using high-performance liquid chromatography. Clearance and changes in clearance were calculated. A first-order pharmacokinetic model was validated by lack of dependence of dose on clearance and an established graphical method. Mean +/- SD infusion rate of dobutamine was 8.2 +/- 5.7 micrograms/kg/min (range 1.7 to 22.3), which resulted in a mean serum concentration of 214 +/- 183 ng/mL (range 15 to 759). The correlation between infusion rate and steady-state dobutamine concentration was r2 = .67. Variability in steady-state dobutamine concentration at various infusion rates was large. Clearance at initial pharmacokinetic analysis averaged 58.4 +/- 33.3 mL/kg/min (range 19 to 120). The percent change in calculated clearance varies from a 72% decrease to an 88% increase, with the greatest variability in clearance occurring during the first 24 hrs of therapy. There was little correlation between initial dobutamine clearance and weight (r2 = .10), net cumulative fluid balance before initiation of dobutamine (r2 < .01), age (r2 = .20), and estimated creatinine clearance (r2 = .09). Dobutamine pharmacokinetics in adult critically ill patients is best described by a first-order model. Pathophysiologic factors may have an effect on the pharmacokinetics of dobutamine which appears to change over time. Both inter- and intrapatient variability in infusion rate administered and resultant serum concentrations were wide, suggesting that infusion rate should be guided by clinical end points rather than by predetermined values.
Anesthesia & Analgesia, 1995
This study was conducted to assess the pulmonary extraction of dobutamine. Eleven patients admitt... more This study was conducted to assess the pulmonary extraction of dobutamine. Eleven patients admitted to the general surgical intensive care unit, with varying diagnoses requiring dobutamine as part of their therapeutic intervention, were included. A single simultaneous sample was drawn, at the clinically required rate of infusion, from the radial and pulmonary artery catheter sites. Total dobutamine clearance was determined using the pulmonary artery (pre-lung) sample. The mean +/- SD total dobutamine clearance was 82 +/- 67 mL.kg-1.min-1 a value which is larger than the average cardiac output of plasma of 56 +/- 20 mL.kg-1.min-1. The mean percent pulmonary extraction fraction of dobutamine was 3.6% +/- 22.5% (range -34-52), a value within the 9% coefficient of variability (CV) of the assay. However, five patients had pulmonary extraction greater than the CV of the assay. Of these five patients, three had "negative" extraction values, and two had "positive" extraction values. There was no relationship between the percent pulmonary extraction of dobutamine and the rate or duration of dobutamine infusion before sampling. The results show that the extraction of dobutamine by the lungs is minimal.
PubMed, Aug 1, 1996
Pharmacists have an integral role in the care of ICU patients, including those with infections. A... more Pharmacists have an integral role in the care of ICU patients, including those with infections. Antibiotics continue to be among the most widely prescribed drugs in the ICU environment. This article focuses on the impact pharmacists have on the care and economics for the critically ill infected patient and on mechanisms used in hospitals to control antibiotic misuse. Numerous studies point to inappropriate antibiotic use and resultant selection pressure on antimicrobial resistance. The critical care pharmacist can impact this prescribing by assuring optimal pharmacotherapy specific for the organism and associated disease. Furthermore, policies have been implemented to modify antibiotic use, including formulary manipulations, antibiotic stop order forms, care plans, antibiotic cycling, oral switching, and computer-assisted antimicrobial therapy. Future research is needed to determine the optimal method for preventing resistance. However, a multidisciplinary approach to rational antimicrobial use is suggested.
PubMed, Jul 5, 2011
Objectives: Current aim of rheumatoid arthritis (RA) treatment is to achieve remission in as many... more Objectives: Current aim of rheumatoid arthritis (RA) treatment is to achieve remission in as many patients as possible. Rates of remission and clinical outcomes after treatment with abatacept in biologic-naive rheumatoid arthritis (RA) patients with early disease and an inadequate response to methotrexate (MTX) versus patients with ≥ 10 years of disease were assessed. Methods: Data from two trials assessing the efficacy of abatacept in MTX inadequate responders were pooled for this exploratory post hoc analysis. Patients with disease duration of ≤ 2 years at baseline (early disease), originally assigned to an abatacept approximately 10 mg/kg treatment arm and entered into a long-term extension (LTE), were compared with patients with ≥ 10 years of disease (long-standing RA). Remission, DAS28-CRP, ACR 70 responses and the Routine Assessment of Patient Index Data 3 (RAPID3), improvement in physical function as measured by the Health Assessment Questionnaire Disability Index (HAQ-DI). Results: Twenty-three percent of these patients (n=108) had early disease. A higher percentage of patients with early disease achieved DAS28-CRP remission versus patients with long-standing disease (35.2% vs. 19.4% at year 1, p<0.01; 46.0% vs. 30.9% at year 3, p<0.05). In addition, a higher percentage of the subgroup with early RA achieved ACR70 responses. More patients with early RA had a meaningful improvement in their HAQ-DI (75.2% vs. 60.4%; p<0.05) and RAPID3 scores at one year (mean changes from baseline of -9.6 vs. -8.1; p=0.009). Conclusions: These data provide additional support for the possible use of abatacept in biologic-naive patients who have had inadequate response to MTX, earlier in their disease course.
Clinical and Applied Thrombosis/Hemostasis
IMPORTANCE Many patients with nonvalvular atrial fibrillation (NVAF) are at a high risk of gastro... more IMPORTANCE Many patients with nonvalvular atrial fibrillation (NVAF) are at a high risk of gastrointestinal (GI) bleeding due to conditions including older age; stage III to V chronic kidney disease (CKD); HAS-BLED (hypertension, kidney or liver disease, stroke history, prior bleeding, unstable international normalized ratio, age >65, drug or alcohol use) score of 3 or greater; corticosteroid, antiplatelet or nonsteroidal anti-inflammatory drug (NSAID) use; or GI conditions. OBJECTIVE To compare the risk of stroke and/or systemic embolism (SE) and major bleeding (MB) among patients with NVAF and high risk of GI bleeding who received non-vitamin K antagonist oral anticoagulants (NOACs) vs those who received warfarin.
BMJ, 2016
Medical Publishing Insights & Practices (MPIP)-a partnership among pharmaceutical companies and t... more Medical Publishing Insights & Practices (MPIP)-a partnership among pharmaceutical companies and the International Society for Medical Publication Professionals-aims to identify ways to improve transparency and credibility in publishing the results of industry sponsored research. This article provides guidance from MPIP on clinically relevant and more informative adverse event reporting, previously identified by journal editors as a significant unmet need to improve patient care and increase the credibility of industry sponsored publications. Our recommendations include highlighting adverse events of most relevance to practitioners and their patients, avoiding broad summary statements such as "generally safe" or "well tolerated," and including more detailed adverse event data (where appropriate) to offer additional clinically important insight. These recommendations complement the earlier recommendations in the Consolidated Standards of Reporting Trials (CONSORT) Harms Extension. Although developed for industry sponsored trials, the adoption of our recommendations would enhance adverse event reporting in clinical research publications regardless of the funding source and thereby facilitate clinical decision making. Summary pointS Objective reporting of adverse event data within clinical trials publications could provide greater context and clarity for the application of trial results to daily clinical practice Conference and manuscript abstracts should include objective information on the incidence and type of clinically relevant adverse events instead of overly general statements such as "well tolerated" Clinically relevant adverse events should be identified and communicated with clarity around relevant clinical characteristics, such as severity, frequency, and timing, which could be more informative than incidence rates Adverse event reporting should include numerators and denominators for all events; formal statistical analyses should be used selectively, and post hoc analyses should be clearly identified
Advances in Therapy
Introduction: Non-valvular atrial fibrillation (NVAF) is often accompanied by multiple comorbid c... more Introduction: Non-valvular atrial fibrillation (NVAF) is often accompanied by multiple comorbid conditions, which increase the associated risks and complexity of patient management. This study evaluated the risk of stroke/systemic embolism (SE) and major bleeding (MB) among multimorbid patients with NVAF who were prescribed non-vitamin K antagonist oral anticoagulants (NOACs) or warfarin. Methods: A retrospective study of patients with NVAF and high multimorbidity who initiated apixaban, dabigatran, rivaroxaban, or warfarin from 1 January 2013 to 30 September 2015 was conducted using five insurance claims databases. Multimorbidity was defined as six or more comorbid conditions, and 1:1 propensity score matching (PSM) was conducted between the NOAC-warfarin and NOAC-NOAC cohorts. Cox proportional hazard models were used to evaluate the hazard ratios of stroke/SE and MB.
The Canadian Journal of Hospital Pharmacy, 2018
European Heart Journal - Cardiovascular Pharmacotherapy
Aims Polypharmacy is prevalent among non-valvular atrial fibrillation (NVAF) patients and present... more Aims Polypharmacy is prevalent among non-valvular atrial fibrillation (NVAF) patients and presents a potential issue for the effective management of NVAF. This study compared the risk of stroke/systemic embolism (SE) and major bleeding (MB) among NVAF patients with polypharmacy newly prescribed oral anticoagulants (OACs). Methods and results A retrospective study of NVAF patients with polypharmacy who initiated OACs from 01 January 2013 to 30 September 2015 was conducted using US CMS Medicare and four commercial databases. Polypharmacy was defined as ≥6 concomitant medications on the index date. Propensity score matching was conducted to compare non-vitamin K antagonists OACs (NOACs) to warfarin as well as between NOACs. Cox proportional hazard models were used to evaluate the risk of stroke/SE and MB. A total of 188 893 patients with polypharmacy were included, with an average of 8 concomitant medications (interquartile range 6–9). Compared to warfarin, apixaban [hazard ratio (HR):...
JAMA Network Open
IMPORTANCE Many patients with nonvalvular atrial fibrillation (NVAF) are at a high risk of gastro... more IMPORTANCE Many patients with nonvalvular atrial fibrillation (NVAF) are at a high risk of gastrointestinal (GI) bleeding due to conditions including older age; stage III to V chronic kidney disease (CKD); HAS-BLED (hypertension, kidney or liver disease, stroke history, prior bleeding, unstable international normalized ratio, age >65, drug or alcohol use) score of 3 or greater; corticosteroid, antiplatelet or nonsteroidal anti-inflammatory drug (NSAID) use; or GI conditions. OBJECTIVE To compare the risk of stroke and/or systemic embolism (SE) and major bleeding (MB) among patients with NVAF and high risk of GI bleeding who received non-vitamin K antagonist oral anticoagulants (NOACs) vs those who received warfarin.
Critical Care Medicine, 1994
Critical Care Medicine, 2000
Objective. To identify and describe the scope of practice that characterizes the critical care ph... more Objective. To identify and describe the scope of practice that characterizes the critical care pharmacist and critical care pharmacy services. Specifically, the goals were to define the level of clinical practice and specialized skills characterizing the critical care pharmacist as clinician, educator, researcher, and manager; and to recommend fundamental, desirable, and optimal pharmacy services and personnel requirements for the provision of pharmaceutical care to critically ill patients. Hospitals having comprehensive resources as well as those with more limited resources were considered. Data Sources. Consensus of critical care pharmacists from institutions of various sizes providing critical care services within several types of pharmacy practice models was obtained, including community-based and academic practice settings. Existing guidelines and literature describing pharmacy practice and drug use processes were reviewed and adapted for the critical care setting. Conclusions. By combining the strengths and expertise of critical care pharmacy specialists with existing supporting literature, these recommendations define the level of clinical practice and specialized skills that characterize the critical care pharmacist as clinician, educator, researcher, and administrator. This position paper recommends fundamental, desirable, and optimal pharmacy services as well as personnel requirements for the provision of pharmaceutical care to critically ill patients.
Critical Care Medicine, 1994
To delineate the variability in the pharmacokinetics of dobutamine over time in an unstable criti... more To delineate the variability in the pharmacokinetics of dobutamine over time in an unstable critically ill adult surgical patient population concurrently receiving therapeutic interventions to optimize oxygen delivery and consumption variables. Prospective study. University hospital adult surgical intensive care unit. Sixteen hemodynamically unstable adults (aged 18 to 84 yrs) requiring dobutamine for inotropic support. None. Samples for dobutamine serum concentration determination were collected at selected times during therapy, following at least 30 mins of a constant infusion rate and measured using high-performance liquid chromatography. Clearance and changes in clearance were calculated. A first-order pharmacokinetic model was validated by lack of dependence of dose on clearance and an established graphical method. Mean +/- SD infusion rate of dobutamine was 8.2 +/- 5.7 micrograms/kg/min (range 1.7 to 22.3), which resulted in a mean serum concentration of 214 +/- 183 ng/mL (range 15 to 759). The correlation between infusion rate and steady-state dobutamine concentration was r2 = .67. Variability in steady-state dobutamine concentration at various infusion rates was large. Clearance at initial pharmacokinetic analysis averaged 58.4 +/- 33.3 mL/kg/min (range 19 to 120). The percent change in calculated clearance varies from a 72% decrease to an 88% increase, with the greatest variability in clearance occurring during the first 24 hrs of therapy. There was little correlation between initial dobutamine clearance and weight (r2 = .10), net cumulative fluid balance before initiation of dobutamine (r2 < .01), age (r2 = .20), and estimated creatinine clearance (r2 = .09). Dobutamine pharmacokinetics in adult critically ill patients is best described by a first-order model. Pathophysiologic factors may have an effect on the pharmacokinetics of dobutamine which appears to change over time. Both inter- and intrapatient variability in infusion rate administered and resultant serum concentrations were wide, suggesting that infusion rate should be guided by clinical end points rather than by predetermined values.
Anesthesia & Analgesia, 1995
This study was conducted to assess the pulmonary extraction of dobutamine. Eleven patients admitt... more This study was conducted to assess the pulmonary extraction of dobutamine. Eleven patients admitted to the general surgical intensive care unit, with varying diagnoses requiring dobutamine as part of their therapeutic intervention, were included. A single simultaneous sample was drawn, at the clinically required rate of infusion, from the radial and pulmonary artery catheter sites. Total dobutamine clearance was determined using the pulmonary artery (pre-lung) sample. The mean +/- SD total dobutamine clearance was 82 +/- 67 mL.kg-1.min-1 a value which is larger than the average cardiac output of plasma of 56 +/- 20 mL.kg-1.min-1. The mean percent pulmonary extraction fraction of dobutamine was 3.6% +/- 22.5% (range -34-52), a value within the 9% coefficient of variability (CV) of the assay. However, five patients had pulmonary extraction greater than the CV of the assay. Of these five patients, three had "negative" extraction values, and two had "positive" extraction values. There was no relationship between the percent pulmonary extraction of dobutamine and the rate or duration of dobutamine infusion before sampling. The results show that the extraction of dobutamine by the lungs is minimal.