Toward better outcomes with tacrolimus therapy: Population pharmacokinetics and individualized dosage prediction in adult liver transplantation

Patient outcomes in transplantation would improve if dosing of immunosuppressive agents was individualized. The aim of this study is to develop a population pharmacokinetic model of tacrolimus in adult liver transplant recipients and test this model in individualizing therapy. Population analysis was performed on data from 68 patients. Estimates were sought for apparent clearance (CL/F) and apparent volume of distribution (V/F) using the nonlinear mixed effects model program (NONMEM). Factors screened for influence on these parameters were weight, age, sex, transplant type, biliary reconstructive procedure, postoperative day, days of therapy, liver function test results, creatinine clearance, hematocrit, corticosteroid dose, and interacting drugs. The predictive performance of the developed model was evaluated through Bayesian forecasting in an independent cohort of 36 patients. No linear correlation existed between tacrolimus dosage and trough concentration (r(2) = 0.005). Mean individual Bayesian estimates for CL/F and V/F were 26.5 8.2 (SD) L/hr and 399 +/- 185 L, respectively. CL/F was greater in patients with normal liver function. V/F increased with patient weight. CL/F decreased with increasing hematocrit. Based on the derived model, a 70-kg patient with an aspartate aminotransferase (AST) level less than 70 U/L would require a tacrolimus dose of 4.7 mg twice daily to achieve a steady-state trough concentration of 10 ng/mL. A 50-kg patient with an AST level greater than 70 U/L would require a dose of 2.6 mg. Marked interindividual variability (43% to 93%) and residual random error (3.3 ng/mL) were observed. Predictions made using the final model were reasonably nonbiased (0.56 ng/mL), but imprecise (4.8 ng/mL). Pharmacokinetic information obtained will assist in tacrolimus dosing; however, further investigation into reasons for the pharmacokinetic variability of tacrolimus is required.

Advanced patient monitoring displays: Tools or continuous informing

We reviewed the use of advanced display technologies for monitoring in anesthesia. Researchers are investigating displays that integrate information and that, in some cases, also deliver the results continuously to the anesthesiologist. Integrated visual displays reveal higher-order properties of patient state and speed in responding to events, but their benefits under an intensely timeshared load is unknown. Head-mounted displays seem to shorten the time to respond to changes, but their impact on peripheral awareness and attention is unknown. Continuous auditory displays extending pulse oximetry seem to shorten response times and improve the ability to time-share other tasks, but their integration into the already noisy operative environment still needs to be tested. We reviewed the advantages and disadvantages of the three approaches, drawing on findings from other fields, such as aviation, to suggest outcomes where there are still no results for the anesthesia context. Proving that advanced patient monitoring displays improve patient outcomes is difficult, and a more realistic goal is probably to prove that such displays lead to better situational awareness, earlier responding, and less workload, all of which keep anesthesia practice away from the outer boundaries of safe operation.

The impact of chronic illness: partnerships with other healthcare professionals

Healthcare workforce shortfalls require a rethinking of models for delivering care to people with chronic disease. Chronic disease needs to be managed by a multiskilled team of healthcare professionals with specialist input. Education at undergraduate, graduate and postgraduate levels needs to prepare healthcare professionals for this new paradigm. Some tasks currently seen only as part of a doctor's purview could be performed by other trained professionals to allow doctors to concentrate on more appropriate activities. We need to explore new collaborations to deliver multidisciplinary healthcare for chronic disease and evaluate these for patient outcomes and cost effectiveness.

Designing effective written health education materials: Considerations for health professionals

Purpose: Written health education materials can only be effective if they can be read, understood, and remembered by patients. The purpose of this article was to review the literature about features that should be incorporated into written health education materials to maximize their effectiveness, identify where there is consensus and debate about which features should be incorporated, and develop recommendations that health professionals can use when reviewing their existing materials and designing new materials. Method: Literature review of published research and education articles. Results: There is a large number of features that need to be considered when designing written health education materials so that they are suitable for the target audience and effective. Although there is consensus about the majority of features that should be included, further research is needed to explore the contribution of certain features, such as illustrations, to the effectiveness of written materials and the effect of well-designed written materials on patient outcomes. Conclusions: Health professionals need to provide their patients with written health education materials that are patient-orientated and designed according to the best practice principles in written health education material design.

Paediatric telecardiology services in Queensland: a review of three years' experience

Videoconferencing at 384 kbit/s for the transmission of echocardiograms has proved useful for the assessment of children with suspected cardiac disease, in regional areas of Queensland. A retrospective review of patient and management outcomes was conducted on cardiac teleconsultations performed at two regional hospitals during the period November 2000 to February 2004, inclusive. There were 106 echo studies. A subset of 72 cardiac teleconsultations performed between May 2001 and February 2004 was reviewed in detail. The median age of patients at the time of consultation was 3 months (range 1 day-17 years). Sixteen per cent of teleconsultations were classified as urgent and were conducted on the same day as referral. Following the videoconference, 90% of patients could be managed locally and reviewed by the paediatrician or visiting paediatric cardiologist during an outreach clinic. Six children (8%) had significant cardiac lesions that were initially managed locally, with subsequent elective transfer at the appropriate time for treatment. Only one child (1%) required urgent transfer to the tertiary centre for specialist care and surgery. Telecardiology was effective in accurately identifying congenital heart disease. Paediatric telecardiology is an evolving modality of assessment and communication, and is likely to result in continued improvements in patient care, patient outcomes and parental satisfaction, in provincial centres removed from the tertiary cardiac centre.

Factors predictive of intravenous fluid administration errors in Australian surgical care wards

Background: Intravenous (IV) fluid administration is an integral component of clinical care. Errors in administration can cause detrimental patient outcomes and increase healthcare costs, although little is known about medication administration errors associated with continuous IV infusions. Objectives: ( 1) To ascertain the prevalence of medication administration errors for continuous IV infusions and identify the variables that caused them. ( 2) To quantify the probability of errors by fitting a logistic regression model to the data. Methods: A prospective study was conducted on three surgical wards at a teaching hospital in Australia. All study participants received continuous infusions of IV fluids. Parenteral nutrition and non-electrolyte containing intermittent drug infusions ( such as antibiotics) were excluded. Medication administration errors and contributing variables were documented using a direct observational approach. Results: Six hundred and eighty seven observations were made, with 124 (18.0%) having at least one medication administration error. The most common error observed was wrong administration rate. The median deviation from the prescribed rate was 247 ml/h (interquartile range 275 to + 33.8 ml/ h). Errors were more likely to occur if an IV infusion control device was not used and as the duration of the infusion increased. Conclusions: Administration errors involving continuous IV infusions occur frequently. They could be reduced by more common use of IV infusion control devices and regular checking of administration rates.

Determinants in the development of advanced nursing practice: a case study of primary-care settings in Hong Kong

Different factors have been shown to influence the development of models of advanced nursing practice (ANP) in primary-care settings. Although ANP is being developed in hospitals in Hong Kong, China, it remains undeveloped in primary care and little is known about the factors determining the development of such a model. The aims of the present study were to investigate the contribution of different models of nursing practice to the care provided in primary-care settings in Hong Kong, and to examine the determinants influencing the development of a model of ANP in such settings. A multiple case study design was selected using both qualitative and quantitative methods of data collection. Sampling methods reflected the population groups and stage of the case study. Sampling included a total population of 41 nurses from whom a secondary volunteer sample was drawn for face-to-face interviews. In each case study, a convenience sample of 70 patients were recruited, from whom 10 were selected purposively for a semi-structured telephone interview. An opportunistic sample of healthcare professionals was also selected. The within-case and cross-case analysis demonstrated four major determinants influencing the development of ANP: (1) current models of nursing practice; (2) the use of skills mix; (3) the perceived contribution of ANP to patient care; and (4) patients' expectations of care. The level of autonomy of individual nurses was considered particularly important. These determinants were used to develop a model of ANP for a primary-care setting. In conclusion, although the findings highlight the complexity determining the development and implementation of ANP in primary care, the proposed model suggests that definitions of advanced practice are appropriate to a range of practice models and cultural settings. However, the findings highlight the importance of assessing the effectiveness of such models in terms of cost and long-term patient outcomes.

Adoption of a sedation scoring system and sedation guideline in an intensive care unit

Aim. The paper presents a study assessing the rate of adoption of a sedation scoring system and sedation guideline. Background. Clinical practice guidelines including sedation guidelines have been shown to improve patient outcomes by standardizing care. In particular sedation guidelines have been shown to be beneficial for intensive care patients by reducing the duration of ventilation. Despite the acceptance that clinical practice guidelines are beneficial, adoption rates are rarely measured. Adoption data may reveal other factors which contribute to improved outcomes. Therefore, the usefulness of the guideline may be more appropriately assessed by collecting adoption data. Method. A quasi-experimental pre-intervention and postintervention quality improvement design was used. Adoption was operationalized as documentation of sedation score every 4 hours and use of the sedation and analgesic medications suggested in the guideline. Adoption data were collected from patients' charts on a random day of the month; all patients in the intensive care unit on that day were assigned an adoption category. Sedation scoring system adoption data were collected before implementation of a sedation guideline, which was implemented using an intensive information-giving strategy, and guideline adoption data were fed back to bedside nurses. After implementation of the guideline, adoption data were collected for both the sedation scoring system and the guideline. The data were collected in the years 2002-2004. Findings. The sedation scoring system was not used extensively in the pre-intervention phase of the study; however, this improved in the postintervention phase. The findings suggest that the sedation guideline was gradually adopted following implementation in the postintervention phase of the study. Field notes taken during the implementation of the sedation scoring system and the guideline reveal widespread acceptance of both. Conclusion. Measurement of adoption is a complex process. Appropriate operationalization contributes to greater accuracy. Further investigation is warranted to establish the intensity and extent of implementation required to positively affect patient outcomes.

Controlled trial of multidisciplinary care teams for acutely ill medical inpatients: enhanced multidisciplinary care

Background: Acute hospital general medicine services care for ageing complex patients, using the skills of a range of health-care providers. Evidence suggests that comprehensive early assessment and discharge planning may improve efficiency and outcomes of care in older medical patients. Aim: To enhance assessment, communication, care and discharge planning by restructuring consistent, patient-centred multidisciplinary teams in a general medicine service. Methods: Prospective controlled trial enrolling 1538 consecutive medical inpatients. Intervention units with additional allied health staff formed consistent multidisciplinary teams aligned with inpatient admitting units rather than wards; implemented improved communication processes for early information collection and sharing between disciplines; and specified shared explicit discharge goals. Control units continued traditional, referral-based multidisciplinary models with existing staffing levels. Results: Access to allied health services was significantly enhanced. There was a trend to reduced index length of stay in the intervention units (7.3 days vs 7.8 days in control units, P = 0.18), with no change in 6-month readmissions. in-hospital mortality was reduced from 6.4 to 3.9% (P = 0.03); less patients experienced functional decline in hospital (P = 0.04) and patients' ratings of health status improved (P = 0.02). Additional staffing costs were balanced by potential bed-day savings. Conclusion: This model of enhanced multidisciplinary inpatient care has provided sustainable efficiency gains for the hospital and improved patient outcomes.

A naturalistic comparison of two right unilateral electroconvulsive therapy dosing protocols: 2-3X seizure threshold versus fixed high-dose

The aim of this study was to compare the outcomes associated with two differing right unilateral (RUL) electroconvulsive therapy (ECT) dosing protocols: 2-3X seizure threshold (2-3X ST) and fixed high dose (FHD) at 353 mC. A retrospective chart review was performed to compare patient outcomes during the implementation of two different dosing protocols: 2-3X ST from October 2000 to May 2001 and FHD from June 2001 to February 2002. A total of 56 patients received ECT under the 2-3X ST protocol, and 46 received ECT under the FHD protocol. In total, 13.6% of patients receiving ECT according to the 2-3X ST protocol received more than 12 ECT, whereas none of the FHD group received more than 12 ECT. The mean number of ECT per treatment course reduced significantly from 7.6 to 5.7 following the switch from the 2-3X ST protocol to the FHD protocol. There were no significant differences between the two groups in the incidence of adverse cognitive effects. ECT practitioners adhered to the 2-3X ST protocol for only 51.8% of ECT courses, with protocol adherence improving to 87% following introduction of the FHD protocol. Although this naturalistic retrospective chart survey had significant methodological limitations, it found that practitioners are more likely to correctly adhere to a fixed dose protocol, therefore, increasing its 'real world' effectiveness in comparison to titrated suprathreshold dosing techniques. The FHD protocol was associated with shorter courses of ECT than the 2-3X ST protocol, with no significant difference between the two protocols in clinically discernable adverse cognitive effects.

A systematic review of successes and failures in home telehealth: preliminary results

We conducted a systematic review of the literature to identify studies in home telehealth that compared a home telehealth intervention with a non-telehealth standard/usual care alternative in terms of administrative changes, patient management decisions, patient outcomes, caregiver outcomes, economic impact or social impact on patients. A search of various databases produced 6643 references. Of these 769 papers were selected for more detailed investigation. These papers, combined with hand searching of relevant telehealth journals and cross-referencing of citations in identified publications, resulted in 138 papers referring to 130 projects for review. In this preliminary analysis we used a quality appraisal approach that took into account the study design. An additional analysis of patient numbers was then used to calculate a net evidence score. A large proportion of studies (80%) were randomised controlled trials. Only 22 projects (17%) reported economic data deemed to be sufficient for appraisal. Evidence exists for the clinical effectiveness of home telehealth in diabetes, the general area of mental health, high risk pregnancy monitoring, heart failure and cardiac disease.

Two knees or not two knees? Patient costs and outcomes following bilateral and unilateral total knee joint replacement surgery for OA

Aims: This study aims to address medical and non-medical direct costs and health outcomes of bilateral and unilateral total knee replacement from the patients' perspective during the first year post-surgery. Methods: Osteoarthritis patients undergoing primary unilateral total knee or bilateral total knee replacement (TKR) surgery at three Sydney hospitals were eligible. Patients completed questionnaires pre-operatively to record expenses during the previous three months and health status immediately prior to surgery. Patients then maintained detailed prospective cost diaries and completed SF-36 and WOMAC Index each three months for the first post-operative year. Results: Pre-operatively, no significant differences in health status were found between patients undergoing unilateral TKR and bilateral TKR. Both unilateral and bilateral TKR patients showed improvements in pain, stiffness and function from pre-surgery to 12 months post-surgery. Patients who had bilateral TKR spent an average of 12.3 days in acute hospital and patients who had unilateral TKR 13.6 days. Totally uncemented prostheses were used in 6% of unilateral replacements and 48% of bilateral replacements. In hospital, patients who had bilateral TKR experienced significantly more complications, mainly thromboembolic, than patients who had unilateral TKR. Regression analysis showed that for every one point increase in the pre-operative SF-36 physical score (i.e. improving physical status) out-of-pocket costs decreased by 94%. Out-of-pocket costs for female patients were 3.3 times greater than for males. Conclusion: Patients undergoing bilateral TKR and unilateral TKR had a similar length of stay in hospital and similar out-of-pocket expenditures. Bilateral replacement patients reported better physical function and general health with fewer health care visits one year post procedure. Patients requiring bilateral TKR have some additional information to aid their decision making. While their risk of peri-operative complications is higher, they have an excellent chance of good health outcomes at 12 months and are not going to be doubly 'out-of-pocket' for the experience. (C) 2004 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Evaluation of clinically relevant changes in patient reported outcomes in knee and hip osteoarthritis: the minimal clinically important improvement

Background: In clinical trials, at the group level, results are usually reported as mean and standard deviation of the change in score, which is not meaningful for most readers. Objective: To determine the minimal clinically important improvement (MCII) of pain, patient's global assessment of disease activity, and functional impairment in patients with knee and hip osteoarthritis (OA). Methods: A prospective multicentre 4 week cohort study involving 1362 outpatients with knee or hip OA was carried out. Data on assessment of pain and patient's global assessment, measured on visual analogue scales, and functional impairment, measured on the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) function subscale, were collected at baseline and final visits. Patients assessed their response to treatment on a five point Likert scale at the final visit. An anchoring method based on the patient's opinion was used. The MCII was estimated in a subgroup of 814 patients ( 603 with knee OA, 211 with hip OA). Results: For knee and hip OA, MCII for absolute ( and relative) changes were, respectively, ( a) -19.9 mm (-40.8%) and -15.3 mm (-32.0%) for pain; ( b) -18.3 mm ( - 39.0%) and -15.2 mm ( -32.6%) for patient's global assessment; ( c) -9.1 ( -26.0%) and -7.9 ( -21.1%) for WOMAC function subscale score. The MCII is affected by the initial degree of severity of the symptoms but not by age, disease duration, or sex. Conclusion: Using criteria such as MCII in clinical trials would provide meaningful information which would help in interpreting the results by expressing them as a proportion of improved patients.