Predictors for unintentional medication reconciliation discrepancies in preadmission medication: a systematic review.

PURPOSE: Discrepancies in preadmission medication (PAM) are common and potentially harmful. Medication reconciliation is able to reduce the discrepancy rate, yet implementation is challenging. In order for reconciliation efforts to be more cost-effective, patients at high risk for reconciliation errors should be identified. The purpose of this systematic review is to identify predictors for unintentional discrepancies in PAM. METHODS: Medline and Embase were searched systematically until June 2017. Only studies concerning adult subjects were retained. Quantitative studies were included if predictors for unintentional discrepancies in the PAM had been determined on hospital admission. Variables were divided into patient-, medication-, and setting-related predictors based on a thematic analysis. Studies on identification of predictors for discrepancies and potentially harmful discrepancies were handled separately. RESULTS: Thirty-five studies were eligible, of which 5 studies focused on potentially harmful discrepancies. The following 16 significant variables were identified using multivariable prediction models: number of preadmission drugs, patient's age, availability of a drug list, patients' understanding of medication, usage of different outpatient pharmacies, number of high-risk drugs, discipline for which the patient is admitted, admitting physician's experience, number and type of consulted sources, patient's gender, type of care before admission, number of outpatient visits during the past year, class of medication, number of reimbursements, use of an electronic prescription system, and type of admission (elective vs emergency). The number of preadmission drugs was identified as a predictor in 20 studies. Potentially harmful discrepancies were ascertained in 5 studies with age found to have a predictive value in all 5 studies. CONCLUSION: Multiple suitable predictors for PAM-related discrepancies were identified of which higher age and polypharmacy were reported most frequently.

Developing a decision rule to optimise clinical pharmacist resources for medication reconciliation in the emergency department.

BACKGROUND: The process of obtaining a complete medication history for patients admitted to the hospital from the ED at hospital admission, without discrepancies, is error prone and time consuming. OBJECTIVES: The goal of this study was the development of a clinical decision rule (CDR) with a high positive predictive value in detecting ED patients admitted to hospital at risk of at least one discrepancy during regular medication history acquisition, along with favourable feasibility considering time and budget constraints. METHODS: Data were based on a previous prospective study conducted at the ED in Belgium, describing discrepancies in 3592 medication histories. Data were split into a training and a validation set. A model predicting the number of discrepancies was derived from the training set with negative binomial regression and was validated on the validation set. The performance of the model was assessed. Several CDRs were constructed and evaluated on positive predictive value and alert rate. RESULTS: The following variables were retained in the prediction model: (1) age, (2) gender, (3) medical discipline for which the patient was admitted, (4) degree of physician training, (5) season of admission, (6) type of care before admission, number of (7) drugs, (8) high-risk drugs, (9) drugs acting on alimentary tract and metabolism, (10) antithrombotics, antihaemorrhagics and antianaemic preparations, (11) cardiovascular drugs, (12) drugs acting on musculoskeletal system and (13) drugs acting on the nervous system; all recorded by the ED physician on admission. The final CDR resulted in an alert rate of 29% with a positive predictive value of 74%. CONCLUSION: The final CDR allows identification of the majority of patients with a potential discrepancy within a feasible workload for the pharmacy staff. Our CDR is a first step towards a rule that could be incorporated into electronic medical records or a scoring system.

Appropriateness of Acid Suppression Therapy.

BACKGROUND: The inappropriate startup of long-term acid suppressive therapy (AST) can have clinical and pharmacoeconomic impacts on ambulatory care. OBJECTIVE: To assess the proportion of patients with appropriate initiation of long-term AST in non-critically ill patients. To describe possible risk factors for nonappropriate AST. To calculate the potential savings when eliminating the nonappropriate startup of AST. METHOD: This observational, retrospective study evaluated the appropriateness of startup of long-term AST in medical records using a broad variety of international criteria and guidelines and using a validated screening instrument. RESULTS: A sample of 597 patients was included in the analysis. In 57% of them, AST was appropriately initiated. No specific risk profile could be defined. There was some indication that the availability of a clinical pharmacist and the use of standing orders were correlated to the outcome. Extrapolation to the total population (ie, 2836 patients) led to a total cost of €8880 during hospital stay plus an extra €40 391 per month after discharge. Avoiding inappropriate initiation of AST could lead to a saving of €3805 plus €17 441 per month. CONCLUSION: In all, 43% of initiation of long-term AST in the hospital was inappropriate. The potential savings from avoiding this could be substantial from a health care payer perspective. No patient characteristics that could predict for inappropriate initiation of AST were identified. A correlation between inappropriate initiation and medical disciplines using standing orders that include AST was seen.

Plasmalyte: No Longer a Culprit in Causing False-Positive Galactomannan Test Results.

False-positive galactomannan (GM) results have been reported in patients treated with gluconate-containing solutions, such as Plasmalyte. The GM optical density index was tested on 33 distinct batches of Plasmalyte and was found to be negative in all of the batches, confirming that Plasmalyte is no longer a cause of false-positive GM results.

Reduced length of stay in radical cystectomy patients with oral versus parenteral post-operative nutrition protocol.

BACKGROUND: In Europe, parenteral nutrition is often used after radical cystectomy to avoid postoperative malnourishment. To the best of our knowledge, however, there is a paucity of data to conclude on the best modality for delivering nutritional support to this patient group. OBJECTIVE: The parenteral nutrition policy was reconsidered and an oral nutrition protocol was implemented by the clinical pharmacist and evaluated in terms of length of stay, number and type of postoperative complications and parenteral nutrition avoided costs. SETTING: A prospective interventional non-randomized before-after study was conducted. Regular radical cystectomy patients presenting without preoperative contra-indications for enteral nutrition were eligible. METHODS: Postoperatively, in the control group, the parenteral nutrition policy from the ward was applied. Parenteral nutrition was initiated systematically and continued until the patient was able to tolerate solid food. In the interventional group, an oral nutrition protocol was implemented. Parenteral nutrition could be initiated if oral intake remained insufficient after 5 days. Main outcome measure The primary end point was postoperative length of stay. Secondary endpoints included the number of patients in whom the oral nutrition protocol was implemented successfully, as well as the number and type of postoperative complications. RESULTS: A total of 94 eligible patients was assigned consecutively to the control (n = 48) and to the interventional group (n = 46). Baseline demographics were comparable. A significant reduction in median length of stay was associated with the oral nutrition protocol [18 days (IQR 15-22) in the control group vs. 14 days (IQR 13-18) in the interventional group (p < 0.001)]. In 40 out of 46 patients from the interventional group, the oral nutrition protocol was implemented successfully. The number and type of postoperative complications did not differ significantly. Implementing the oral nutrition protocol resulted in a direct parenteral nutrition infusion bag cost saving of approximately €512 and a reduction in hospitalization cost of €2,608 per patient. CONCLUSION: The findings of our study showed that an oral nutrition protocol, when compared to the systematic postoperative use of parenteral nutrition, was associated with a decreased length of stay and costs in a regular radical cystectomy patient population.

Outcome Indicators for Home Parenteral Nutrition Care: Point of View From Adult Patients With Benign Disease.

BACKGROUND AND AIMS: Patients receiving home parenteral nutrition (HPN) deserve a high-quality and patient-centered care. Patient-centered care can be delivered only if the patient's priorities and concerns are known. Therefore, the aim is to identify the top 3 most important outcome indicators according to patients' perspectives and the differences between several centers, HPN regimen, and HPN experience. METHODS: A questionnaire, based on previously developed outcome indicators, was translated into the mother tongue using forward-backward translation and distributed to adult HPN patients with benign disease in March 2013. To identify differences, a Kruskal-Wallis or Mann-Whitney test was performed with GraphPad Prism (significance level <.05) when applicable. RESULTS: Nine centers over 8 countries (300 patients) participated. The top 3 outcome indicators for patients were (1) incidence of catheter-related infection (CRI), (2) survival, and (3) quality of life (QoL). Between the participating centers, significant differences on rating were found for 5 outcome indicators (catheter obstruction, .015; weight, .002; energy, .010; fear, <.001; and independence, .010). The independence outcome indicator (.050) was considered less important for experienced (>2 years HPN) vs less experienced patients. For this outcome indicator, patients' view also differed significantly based on number of HPN days per week (.0103). CONCLUSION: A cohort of HPN patients identified incidence of CRI, survival, and QoL as the most important outcome indicators for their care; however, there were significant differences between the participating centers. For one outcome indicator (independence), there were significant differences based on experience and regimen.

Identifying patient-centered quality indicators for the care of adult home parenteral nutrition (HPN) patients.

BACKGROUND: Previous qualitative research, aimed at eliciting the experiences and views of home parenteral nutrition (HPN) patients in daily life, revealed little information on HPN care. However, to perform patient-centered care, it is important to understand what "quality of care" means for adult HPN patients. Therefore, the aim of this study was to identify quality indicators through patients' perspectives. MATERIALS AND METHODS: In-depth, face-to-face, semistructured interviews were conducted between June and November 2011 with adult patients who recently started HPN. Patients were selected by purposive sampling. Interviews were audio recorded, transcribed verbatim, and analyzed using a framework approach. Nvivo 9.0 software was used for managing transcripts. RESULTS: Twelve adult patients (7F/5M) were interviewed. At the time of the interview, median HPN experience was 59 days. Two structure, 31 process, and 9 outcome indicators were identified. The majority of process indicators are related to the home nurse, indicating the important role of these healthcare professionals in HPN care. In addition, all interviewees reported communication as an essential aspect of the complex care pathway. The identified outcome indicators are comparable with the indicators that were previously developed by an expert panel. For example, improvement in quality of life during HPN treatment and incidence of catheter-related infections were identified by both groups. CONCLUSION: Interviews with HPN patients revealed an interesting set of indicators that can be used to perform, evaluate, or improve current HPN care and are a starting point for a more patient-centered approach.

The Eagle-like effect of echinocandins: what's in a name?

Despite several years of research, a lot of questions remain about the paradoxical attenuation of echinocandin activity against Candida and Aspergillus species at certain drug concentrations above the MIC values, the so-called paradoxical growth effect or Eagle-like effect. Although this phenomenon has been observed in several in vitro studies, confirming in vivo data are scarce. The clinical relevance remains unknown, although more and more data suggest that the clinical impact of this phenomenon might be heavily overrated. Detailed knowledge about the mechanisms responsible for this phenomenon and further research about the presence of the effect in the human body is necessary to decide whether the paradoxical growth effect of echinocandins can really interfere with an adequate treatment of invasive fungal diseases in clinical practice.

Pharmacokinetic profile of voriconazole in a critically ill patient on therapeutic plasma exchange.

BACKGROUND: Extracorporeal removal of drugs during therapeutic plasma exchange (TPE) can lead to decreased efficacy, as shown in several reports discussing altered pharmacokinetics (PKs) of antibiotics during TPE. In particular, drugs with a low volume of distribution or a high protein binding are susceptible to extracorporeal removal, as these drugs remain substantially within the intravascular space. No information is known about antifungal drug removal during TPE. We report the PKs of voriconazole in a critically ill patient undergoing TPE. METHODS: A 61-year-old man, presenting with catastrophic antiphospholipid syndrome for which TPE was started, developed probable pulmonary invasive aspergillosis. Intravenous voriconazole was started. Blood samples were taken under steady state conditions to calculate PK parameters of voriconazole, both with and without TPE. RESULTS: PK parameters (area under the curve, Cl, Vd, and t1/2) were equivalent on both days. Voriconazole has a distribution volume of 4.5 L/kg and a protein binding of 58%, suggesting that drug removal during TPE would not be clinically significant. Our data support this assumption. CONCLUSION: Based on our findings, it seems that TPE does not alter the PK behavior of voriconazole. Voriconazole dosages should not be adjusted during TPE.

Epidemiology of catheter-related infections in adult patients receiving home parenteral nutrition: a systematic review.

BACKGROUND AND AIMS: Catheter-related infection (CRI) is the most common and serious complication for adult patients receiving home parenteral nutrition (HPN). Our aim is to provide epidemiological data on infection incidence, infecting pathogens and contributing risk factors. METHODS: Four electronic databases (Embase, Medline, IPA, CINAHL) were screened for eligible studies published between 1970 and March 2012. Methodological quality was evaluated and terminology/definitions were re-categorized. RESULTS: Thirty-nine studies were included. Extensive variability was observed in terminology/definitions as well as in expression of CRI rate. After correct interpretation of definitions, overall catheter-related bloodstream infection rate (CRBSI) ranged between 0.38 and 4.58 episodes/1000 catheter days (median 1.31). Gram-positive bacteria of human skin flora caused more than half of infections. An analysis of the reported risk factors showed that the origin of a CRBSI is often multifactorial. The risk factors were related to the patient, the venous access device, the education, HPN therapy and follow-up. CONCLUSIONS: This review on CRI in adult HPN patients revealed that included studies are of low quality and used poorly described risk factors and different definitions. The human skin flora caused most of infections; therefore, hand hygiene and training remain essential.

Quality of care for cancer patients on home parenteral nutrition: development of key interventions and outcome indicators using a two-round Delphi approach.

PURPOSE: Clear recommendations on how to guide patients with cancer on home parenteral nutrition (HPN) are lacking as the use of HPN in this population remains a controversial issue. Therefore, the aims of this study were to rank treatment recommendations and main outcome indicators to ensure high-quality care and to indicate differences in care concerning benign versus malignant patients. METHODS: Treatment recommendations, identified from published guidelines, were used as a starting point for a two-round Delphi approach. Comments and additional interventions proposed in the first round were reevaluated in the second round. Ordinal logistic regression with SPSS 2.0 was used to identify differences in care concerning benign versus malignant patients. RESULTS: Twenty-seven experts from five European countries completed two Delphi rounds. After the second Delphi round, the top three most important outcome indicators were (1) quality of life (QoL), (2) incidence of hospital readmission and (3) incidence of catheter-related infections. Forty-two interventions were considered as important for quality of care (28/42 based on published guidelines; 14/42 newly suggested by Delphi panel). The topics 'Liver disease' and 'Metabolic bone disease' were considered less important for cancer patients, together with use of infusion pumps (p = 0.004) and monitoring of vitamins and trace elements (p = 0.000). Monitoring of QoL is considered more important for cancer patients (p = 0.03). CONCLUSION: Using a two-round Delphi approach, we developed a minimal set of 42 interventions that may be used to determine quality of care in HPN patients with malignancies. This set of interventions differs from a similar set developed for benign patients.

Development of quality of care interventions for adult patients on home parenteral nutrition (HPN) with a benign underlying disease using a two-round Delphi approach.

BACKGROUND & AIMS: HPN patients with benign diseases deserve professional care as they have to deal with complex techniques and risk potentially dangerous complications. The aim was to highlight main outcome quality indicators and to develop a set of key interventions to direct multidisciplinary teams in providing qualitative care. METHODS: A two-round Delphi approach was used to build consensus on the most important outcome indicators and on 59 interventions identified in existing guidelines on HPN. Comments and interventions newly identified in the first round were co-evaluated in the second round. RESULTS: 29 experts from 9 countries completed the two-round Delphi approach. The outcome indicators rated as the most important are 1) incidence of catheter-related infections, 2) incidence of readmission and quality of life (shared second place) and 3) incidence of dehydration. Sixty eight of a total of 89 interventions were considered as important for the quality of care, of which 46 are based on published guidelines and 22 were newly suggested by the Delphi panel. CONCLUSIONS: Using a two-round Delphi approach, consensus was reached for the majority of interventions concerning HPN patients with benign diseases. This set of 68 interventions could be of use as a starting point for quality-improvement programs.

The impact of a transjugular intrahepatic portosystemic shunt on the pharmacokinetics of caspofungin in a critically ill patient.

BACKGROUND: Caspofungin is the first echinocandin approved for the treatment of invasive fungal infections (IFI). As it is also well tolerated in patients with liver cirrhosis, caspofungin is an alternative for azoles in the treatment of IFI in patients with hepatic insufficiency. METHODS: We report, for the first time, the pharmacokinetics (PK) of caspofungin in a patient with Child A cirrhosis and a transjugular intrahepatic portosystemic shunt (TIPS) and compare values to previously published results. RESULTS: Caspofungin plasma levels were determined on days 14 (before TIPS reduction) and 29 (after TIPS reduction) of treatment. Troughs and peaks were 3.55 and 3.34 mg/l on day 14 and 9.28 and 9.49 mg/l on day 29, resulting in, (1) PK parameters only slightly higher than previously reported results in healthy volunteers and patients with Child A liver cirrhosis without TIPS and (2) similar exposures before versus after TIPS reduction. This limited increase in exposure is not expected to be correlated to toxicity. CONCLUSION: Caspofungin is a safe alternative for azoles when treating patients with TIPS suffering from IFI.

Augmented renal clearance in the critically ill: how to assess kidney function.

BACKGROUND: Augmented renal clearance in critically ill patients can result in underdosing of life-saving drugs, potentially leading to therapeutic failure. To detect this phenomenon, correct assessment of the kidney function is essential. Currently, little is known about the validity of mathematical formulas to estimate renal function in this subset of patients. OBJECTIVE: To evaluate the validity of different methods to estimate kidney function in critically ill patients with augmented renal clearance by comparing measured renal clearance with estimated clearance using different formulas. METHODS: An observational, retrospective, single-center study was conducted in a 34-bed surgical intensive care unit (SICU) of the University Hospitals Leuven, Leuven, Belgium. Adults admitted to the SICU in 2010 with a measured creatinine clearance (CrCl) of 120 mL/min or more (based on 24-hour urinary collection) were included. The measured clearance values were compared with estimated clearance values as calculated by the Cockcroft-Gault (CrCl(CG)) method and the reexpressed 4-variable Modification of Diet in Renal Disease estimated glomerular filtration rate (eGFR) formula. Spearman rank order correlation was performed to determine the relationship between measured and estimated clearances. Bland-Altman plots were evaluated to assess bias and limits of agreement between the 2 methods. RESULTS: Records on 1317 patients were screened. Augmented renal clearance was present in 390 patients. Spearman correlation showed fair correlation between measured and estimated clearances (r(s) = 0.343; p < 0.001 [CrCl(CG)] and r(s) = 0.290; p < 0.001 [eGFR]). Bias was -11.2 mL/min with limits of agreement (-131.7; 109.3 mL/min [CrCl(CG)]) and -19.9 mL/min with limits of agreement (-170.4; 130.7 mL/min [eGFR]). CONCLUSIONS: Estimated renal clearances, such as the eGFR estimated by the MDRD formula or CrCl estimated by CG, showed poor agreement with measured CrCl values in our critically ill population displaying augmented renal clearance. Clinicians should be cautious when interpreting kidney function based on estimating equations in this subset of patients. Instead, measured CrCl using urinary collection is recommended in patients suspected of displaying augmented renal clearance.

Guidelines recommendations on care of adult patients receiving home parenteral nutrition: a systematic review of global practices.

BACKGROUND & AIMS: Because home parenteral nutrition (HPN) in adult patients can give rise to a variety of complications, good guidance is necessary. To achieve this, clarity and consistency in guidelines are essential. The aim of this review is to identify and compare evidence-based guidelines, and to compile a list of main recommendations, according to their evidence-based grade. METHODS: We searched Medline and the international guideline database for HPN guidelines, performed a content analysis of retrieved guidelines, and evaluated their quality. We then compiled a comparative table of guideline recommendations along with their assigned level of evidence. SUMMARY OF RESULTS: Six systematically developed evidence-based guidelines and one expert opinion-based standard for home care were retrieved. Of these guidelines, two were exclusively devoted to HPN. Although the guidelines generally covered the same topics, most did not provide information on intravenous medication, bone metabolic disease, and indications in patients with malignant disease. Moreover, we found grading discrepancies among various guidelines, as identical recommendations were often labeled with different grades. CONCLUSION: Our comparison of guidelines and standards for HPN revealed substantial differences among recommendations. Identification of these discrepancies and omissions should facilitate the development of more comprehensive and better justified guidelines in the future.

Stability of therapeutic albumin solutions used for molecular adsorbent recirculating system-based liver dialysis.

Mounting evidence suggests beneficial effects of albumin dialysis-based liver support in patients suffering from acute-on-chronic liver failure. Molecular adsorbent recirculating system (MARS) is a nonbiological liver support device, based on the exchange of albumin-bound toxins between the patient's blood and a 20% human serum albumin solution in a secondary circuit. Bound toxins are continuously removed from the circulating albumin by exposure to activated charcoal and an ion-exchange resin. The aim of the present in vitro study was to determine the impact of exposure to charcoal and resin on the ligand binding properties of albumins, containing various levels of stabilizers and obtained from different suppliers (Baxter, CAF-DCF [Red Cross], and Sigma-Aldrich). Albumin binding properties were assessed by measuring equilibrium binding properties of warfarin, diazepam, and salicylate before and after incubation (for up to 7 h) with adsorbing materials; albumin-associated esterase-like activities were also determined. Notable changes in albumin binding upon incubation with adsorbing materials were only observed when using warfarin as a ligand. Affinity of warfarin for the Baxter and Sigma albumins showed a pronounced decrease (higher K(d) ) after the 1-7-h exposure to charcoal or resin. In the absence of adsorbing materials, similar effects were found, indicating that incubation time per se affects albumin binding properties. Following exposure to resin, Baxter albumin binding capacity (B(max)) increased about twofold. For albumin obtained from CAF-DCF, binding affinity and capacity for warfarin were constant under all conditions tested. Esterase-like activities associated with these albumins were either maintained or enhanced (up to 2.5-fold in case of Sigma albumin) following 7-h incubations with adsorbing materials. Our data suggest limited direct influence of the presence of stabilizers in therapeutic albumin solutions on baseline binding properties of human albumin. However, in vitro incubations of these albumins for several hours resulted in supplier-specific changes in warfarin binding, suggesting an influence of stabilizers on the stability of binding properties. Further preclinical and clinical studies are required to elucidate the clinical relevance of these in vitro results, that is, to what extent these changes in albumin binding properties result in altered performance of albumins in the secondary circuit during the MARS procedure.