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1.  Point-of-Care International Normalized Ratio (INR) Monitoring Devices for Patients on Long-term Oral Anticoagulation Therapy 
Executive Summary
Subject of the Evidence-Based Analysis
The purpose of this evidence based analysis report is to examine the safety and effectiveness of point-of-care (POC) international normalized ratio (INR) monitoring devices for patients on long-term oral anticoagulation therapy (OAT).
Clinical Need: Target Population and Condition
Long-term OAT is typically required by patients with mechanical heart valves, chronic atrial fibrillation, venous thromboembolism, myocardial infarction, stroke, and/or peripheral arterial occlusion. It is estimated that approximately 1% of the population receives anticoagulation treatment and, by applying this value to Ontario, there are an estimated 132,000 patients on OAT in the province, a figure that is expected to increase with the aging population.
Patients on OAT are regularly monitored and their medications adjusted to ensure that their INR scores remain in the therapeutic range. This can be challenging due to the narrow therapeutic window of warfarin and variation in individual responses. Optimal INR scores depend on the underlying indication for treatment and patient level characteristics, but for most patients the therapeutic range is an INR score of between 2.0 and 3.0.
The current standard of care in Ontario for patients on long-term OAT is laboratory-based INR determination with management carried out by primary care physicians or anticoagulation clinics (ACCs). Patients also regularly visit a hospital or community-based facility to provide a venous blood samples (venipuncture) that are then sent to a laboratory for INR analysis.
Experts, however, have commented that there may be under-utilization of OAT due to patient factors, physician factors, or regional practice variations and that sub-optimal patient management may also occur. There is currently no population-based Ontario data to permit the assessment of patient care, but recent systematic reviews have estimated that less that 50% of patients receive OAT on a routine basis and that patients are in the therapeutic range only 64% of the time.
Overview of POC INR Devices
POC INR devices offer an alternative to laboratory-based testing and venipuncture, enabling INR determination from a fingerstick sample of whole blood. Independent evaluations have shown POC devices to have an acceptable level of precision. They permit INR results to be determined immediately, allowing for more rapid medication adjustments.
POC devices can be used in a variety of settings including physician offices, ACCs, long-term care facilities, pharmacies, or by the patients themselves through self-testing (PST) or self-management (PSM) techniques. With PST, patients measure their INR values and then contact their physician for instructions on dose adjustment, whereas with PSM, patients adjust the medication themselves based on pre-set algorithms. These models are not suitable for all patients and require the identification and education of suitable candidates.
Potential advantages of POC devices include improved convenience to patients, better treatment compliance and satisfaction, more frequent monitoring and fewer thromboembolic and hemorrhagic complications. Potential disadvantages of the device include the tendency to underestimate high INR values and overestimate low INR values, low thromboplastin sensitivity, inability to calculate a mean normal PT, and errors in INR determination in patients with antiphospholipid antibodies with certain instruments. Although treatment satisfaction and quality of life (QoL) may improve with POC INR monitoring, some patients may experience increased anxiety or preoccupation with their disease with these strategies.
Evidence-Based Analysis Methods
Research Questions
1. Effectiveness
Does POC INR monitoring improve clinical outcomes in various settings compared to standard laboratory-based testing?
Does POC INR monitoring impact patient satisfaction, QoL, compliance, acceptability, convenience compared to standard laboratory-based INR determination?
Settings include primary care settings with use of POC INR devices by general practitioners or nurses, ACCs, pharmacies, long-term care homes, and use by the patient either for PST or PSM.
2. Cost-effectiveness
What is the cost-effectiveness of POC INR monitoring devices in various settings compared to standard laboratory-based INR determination?
Inclusion Criteria
English-language RCTs, systematic reviews, and meta-analyses
Publication dates: 1996 to November 25, 2008
Population: patients on OAT
Intervention: anticoagulation monitoring by POC INR device in any setting including anticoagulation clinic, primary care (general practitioner or nurse), pharmacy, long-term care facility, PST, PSM or any other POC INR strategy
Minimum sample size: 50 patients Minimum follow-up period: 3 months
Comparator: usual care defined as venipuncture blood draw for an INR laboratory test and management provided by an ACC or individual practitioner
Outcomes: Hemorrhagic events, thromboembolic events, all-cause mortality, anticoagulation control as assessed by proportion of time or values in the therapeutic range, patient reported outcomes including satisfaction, QoL, compliance, acceptability, convenience
Exclusion criteria
Non-RCTs, before-after studies, quasi-experimental studies, observational studies, case reports, case series, editorials, letters, non-systematic reviews, conference proceedings, abstracts, non-English articles, duplicate publications
Studies where POC INR devices were compared to laboratory testing to assess test accuracy
Studies where the POC INR results were not used to guide patient management
Method of Review
A search of electronic databases (OVID MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, The Cochrane Library, and the International Agency for Health Technology Assessment [INAHTA] database) was undertaken to identify evidence published from January 1, 1998 to November 25, 2008. Studies meeting the inclusion criteria were selected from the search results. Reference lists of selected articles were also checked for relevant studies.
Summary of Findings
Five existing reviews and 22 articles describing 17 unique RCTs met the inclusion criteria. Three RCTs examined POC INR monitoring devices with PST strategies, 11 RCTs examined PSM strategies, one RCT included both PST and PSM strategies and two RCTs examined the use of POC INR monitoring devices by health care professionals.
Anticoagulation Control
Anticoagulation control is measured by the percentage of time INR is within the therapeutic range or by the percentage of INR values in the therapeutic range. Due to the differing methodologies and reporting structures used, it was deemed inappropriate to combine the data and estimate whether the difference between groups would be significant. Instead, the results of individual studies were weighted by the number of person-years of observation and then pooled to calculate a summary measure.
Across most studies, patients in the intervention groups tended to have a higher percentage of time and values in the therapeutic target range in comparison to control patients. When the percentage of time in the therapeutic range was pooled across studies and weighted by the number of person-years of observation, the difference between the intervention and control groups was 4.2% for PSM, 7.2% for PST and 6.1% for POC use by health care practitioners. Overall, intervention patients were in the target range 69% of the time and control patients were in the therapeutic target range 64% of the time leading to an overall difference between groups of roughly 5%.
Major Complications and Deaths
There was no statistically significant difference in the number of major hemorrhagic events between patients managed with POC INR monitoring devices and patients managed with standard laboratory testing (OR =0.74; 95% CI: 0.52- 1.04). This difference was non-significant for all POC strategies (PSM, PST, health care practitioner).
Patients managed with POC INR monitoring devices had significantly fewer thromboembolic events than usual care patients (OR =0.52; 95% CI: 0.37 - 0.74). When divided by POC strategy, PSM resulted in significantly fewer thromboembolic events than usual care (OR =0.46.; 95% CI: 0.29 - 0.72). The observed difference in thromboembolic events for PSM remained significant when the analysis was limited to major thromboembolic events (OR =0.40; 95% CI: 0.17 - 0.93), but was non-significant when the analysis was limited to minor thromboembolic events (OR =0.73; 95% CI: 0.08 - 7.01). PST and GP/Nurse strategies did not result in significant differences in thromboembolic events, however there were only a limited number of studies examining these interventions.
No statistically significant difference was observed in the number of deaths between POC intervention and usual care control groups (OR =0.67; 95% CI: 0.41 - 1.10). This difference was non-significant for all POC strategies. Only one study reported on survival with 10-year survival rate of 76.1% in the usual care control group compared to 84.5% in the PSM group (P=0.05).
Summary Results of Meta-Analyses of Major Complications and Deaths in POC INR Monitoring Studies
Patient Satisfaction and Quality of Life
Quality of life measures were reported in eight studies comparing POC INR monitoring to standard laboratory testing using a variety of measurement tools. It was thus not possible to calculate a quantitative summary measure. The majority of studies reported favourable impacts of POC INR monitoring on QoL and found better treatment satisfaction with POC monitoring. Results from a pre-analysis patient and caregiver focus group conducted in Ontario also indicated improved patient QoL with POC monitoring.
Quality of the Evidence
Studies varied with regard to patient eligibility, baseline patient characteristics, follow-up duration, and withdrawal rates. Differential drop-out rates were observed such that the POC intervention groups tended to have a larger number of patients who withdrew. There was a lack of consistency in the definitions and reporting for OAT control and definitions of adverse events. In most studies, the intervention group received more education on the use of warfarin and performed more frequent INR testing, which may have overestimated the effect of the POC intervention. Patient selection and eligibility criteria were not always fully described and it is likely that the majority of the PST/PSM trials included a highly motivated patient population. Lastly, a large number of trials were also sponsored by industry.
Despite the observed heterogeneity among studies, there was a general consensus in findings that POC INR monitoring devices have beneficial impacts on the risk of thromboembolic events, anticoagulation control and patient satisfaction and QoL (ES Table 2).
GRADE Quality of the Evidence on POC INR Monitoring Studies
CI refers to confidence interval; Interv, intervention; OR, odds ratio; RCT, randomized controlled trial.
Economic Analysis
Using a 5-year Markov model, the health and economic outcomes associated with four different anticoagulation management approaches were evaluated:
Standard care: consisting of a laboratory test with a venipuncture blood draw for an INR;
Healthcare staff testing: consisting of a test with a POC INR device in a medical clinic comprised of healthcare staff such as pharmacists, nurses, and physicians following protocol to manage OAT;
PST: patient self-testing using a POC INR device and phoning in results to an ACC or family physician; and
PSM: patient self-managing using a POC INR device and self-adjustment of OAT according to a standardized protocol. Patients may also phone in to a medical office for guidance.
The primary analytic perspective was that of the MOHLTC. Only direct medical costs were considered and the time horizon of the model was five years - the serviceable life of a POC device.
From the results of the economic analysis, it was found that POC strategies are cost-effective compared to traditional INR laboratory testing. In particular, the healthcare staff testing strategy can derive potential cost savings from the use of one device for multiple patients. The PSM strategy, however, seems to be the most cost-effective method i.e. patients are more inclined to adjust their INRs more readily (as opposed to allowing INRs to fall out of range).
Considerations for Ontario Health System
Although the use of POC devices continues to diffuse throughout Ontario, not all OAT patients are suitable or have the ability to practice PST/PSM. The use of POC is currently concentrated at the institutional setting, including hospitals, ACCs, long-term care facilities, physician offices and pharmacies, and is much less commonly used at the patient level. It is, however, estimated that 24% of OAT patients (representing approximately 32,000 patients in Ontario), would be suitable candidates for PST/PSM strategies and willing to use a POC device.
There are several barriers to the use and implementation of POC INR monitoring devices, including factors such as lack of physician familiarity with the devices, resistance to changing established laboratory-based methods, lack of an approach for identifying suitable patients and inadequate resources for effective patient education and training. Issues of cost and insufficient reimbursement strategies may also hinder implementation and effective quality assurance programs would need to be developed to ensure that INR measurements are accurate and precise.
For a select group of patients who are highly motivated and trained, PSM resulted in significantly fewer thromboembolic events compared to conventional laboratory-based INR testing. No significant differences were observed for major hemorrhages or all-cause mortality. PST and GP/Nurse use of POC strategies are just as effective as conventional laboratory-based INR testing for thromboembolic events, major hemorrhages, and all-cause mortality. POC strategies may also result in better OAT control as measured by the proportion of time INR is in the therapeutic range and there appears to be beneficial impacts on patient satisfaction and QoL. The use of POC devices should factor in patient suitability, patient education and training, health system constraints, and affordability.
anticoagulants, International Normalized Ratio, point-of-care, self-monitoring, warfarin.
PMCID: PMC3377545  PMID: 23074516
2.  Comparison of warfarin therapy clinical outcomes following implementation of an automated mobile phone-based critical laboratory value text alert system 
BMC Medical Genomics  2014;7(Suppl 1):S13.
Computerized alert and reminder systems have been widely accepted and applied to various patient care settings, with increasing numbers of clinical laboratories communicating critical laboratory test values to professionals via either manual notification or automated alerting systems/computerized reminders. Warfarin, an oral anticoagulant, exhibits narrow therapeutic range between treatment response and adverse events. It requires close monitoring of prothrombin time (PT)/international normalized ratio (INR) to ensure patient safety. This study was aimed to evaluate clinical outcomes of patients on warfarin therapy following implementation of a Personal Handy-phone System-based (PHS) alert system capable of generating and delivering text messages to communicate critical PT/INR laboratory results to practitioners' mobile phones in a large tertiary teaching hospital.
A retrospective analysis was performed comparing patient clinical outcomes and physician prescribing behavior following conversion from a manual laboratory result alert system to an automated system. Clinical outcomes and practitioner responses to both alert systems were compared. Complications to warfarin therapy, warfarin utilization, and PT/INR results were evaluated for both systems, as well as clinician time to read alert messages, time to warfarin therapy modification, and monitoring frequency.
No significant differences were detected in major hemorrhage and thromboembolism, warfarin prescribing patterns, PT/INR results, warfarin therapy modification, or monitoring frequency following implementation of the PHS text alert system. In both study periods, approximately 80% of critical results led to warfarin discontinuation or dose reduction. Senior physicians' follow-up response time to critical results was significantly decreased in the PHS alert study period (46.3% responded within 1 day) compared to the manual notification study period (24.7%; P = 0.015). No difference in follow-up response time was detected for junior physicians.
Implementation of an automated PHS-based text alert system did not adversely impact clinical or safety outcomes of patients on warfarin therapy. Approximately 80% immediate recognition of text alerts was achieved. The potential benefits of an automated PHS alert for senior physicians were demonstrated.
PMCID: PMC4101312
3.  Use of reminders to increase compliance with tetanus booster vaccination. 
OBJECTIVE: To assess the effect of three computerized reminder systems on compliance with tetanus vaccination. DESIGN: Prospective randomized controlled trial. SETTING: Ottawa Civic Hospital Family Medicine Centre. PARTICIPANTS: Of 8069 patients 20 years of age or more who were not in a hospital or institution 5589 were randomly assigned, by family, to a control group, a physician reminder group, a telephone reminder group or a letter reminder group. The remaining 2480 patients were not included in the randomized portion of the study but were monitored. Results are presented for the 5242 randomized patients and the 2369 nonrandomized patients for whom there was no up-to-date record of tetanus vaccination at the start of the trial. INTERVENTIONS: For the patients in the physician reminder group the physician was reminded at an office visit to assess the patient's tetanus vaccination status and to recommend vaccination; those in the other two reminder groups received a telephone call or letter enquiring about their tetanus vaccination status and recommending a booster dose. MAIN OUTCOME MEASURE: Proportion of patients who received tetanus toxoid during the study year or who had a claim of vaccination in the previous 10 years. MAIN RESULTS: The rate of recorded tetanus vaccination in the randomized control group was 3.2%. The difference between that rate and those for the three reminder groups was 19.6% in the physician reminder group (95% confidence interval [CI] 17.1% to 22.2%, p less than 0.00001), 20.8% in the telephone reminder group (95% CI 18.3% to 23.5%, p less than 0.00001) and 27.4% in the letter reminder group (95% CI 24.8% to 30.2%, p less than 0.00001)). The letter reminders were more effective than either the telephone reminders (p = 0.00013) or the physician reminders (p less than 0.00001) in improving compliance. The cost to the practice per additional vaccination recorded was 43 for the physician reminders, $5.43 for the telephone reminders and $6.05 for the letter reminders. CONCLUSIONS: Although all three reminder systems increased the rate of recorded tetanus vaccination they fell far short of achieving complete population coverage. More intensive interventions would be required to approach that goal. However, such interventions do not appear to be justified given the rarity of tetanus.
PMCID: PMC1488617  PMID: 1544078
4.  The management of non-valvular atrial fibrillation (NVAF) in Australian general practice: bridging the evidence-practice gap. A national, representative postal survey 
BMC Family Practice  2008;9:62.
General practitioners (GPs) are ideally placed to bridge the widely noted evidence-practice gap between current management of NVAF and the need to increase anticoagulant use to reduce the risk of fatal and disabling stroke in NVAF. We aimed to identify gaps in current care, and asked GPs to identify potentially useful strategies to overcome barriers to best practice.
We obtained contact details for a random sample of 1000 GPs from a national commercial data-base. Randomly selected GPs were mailed a questionnaire after an advance letter. Standardised reminders were administered to enhance response rates. As part of a larger survey assessing GP management of NVAF, we included questions to explore GPs' risk assessment, estimates of stroke risk and GPs' perceptions of the risks and benefits of anticoagulation with warfarin. In addition, we explored GPs' perceived barriers to the wider uptake of anticoagulation, quality control of anticoagulation and their assessment of strategies to assist in managing NVAF.
596 out of 924 eligible GPs responded (64.4% response rate). The majority of GPs recognised that the benefits of warfarin outweighed the risks for three case scenarios in which warfarin is recommended according to Australian guidelines. In response to a hypothetical case scenario describing a patient with a supratherapeutic INR level of 5, 41.4% of the 596 GPs (n = 247) and 22.0% (n = 131) would be "highly likely" or "likely", respectively, to cease warfarin therapy and resume at a lower dose when INR levels are within therapeutic range. Only 27.9% (n = 166/596) would reassess the patient's INR levels within one day of recording the supratherapeutic INR. Patient contraindications to warfarin was reported to "usually" or "always" apply to the patients of 40.6% (n = 242/596) of GPs when considering whether or not to prescribe warfarin. Patient refusal to take warfarin "usually" or "always" applied to the patients of 22.3% (n = 133/596) of GPs. When asked to indicate the usefulness of strategies to assist in managing NVAF, the majority of GPs (89.1%, n = 531/596) reported that they would find patient educational resources outlining the benefits and risks of available treatments "quite useful" or "very useful". Just under two-thirds (65.2%; n = 389/596) reported that they would find point of care INR testing "quite" or "very" useful. An outreach specialist service and training to enable GPs to practice stroke medicine as a special interest were also considered to be "quite" or "very useful" by 61.9% (n = 369/596) GPs.
This survey identified gaps, based on GP self-report, in the current care of NVAF. GPs themselves have provided guidance on the selection of implementation strategies to bridge these gaps. These results may inform future initiatives designed to reduce the risk of fatal and disabling stroke in NVAF.
PMCID: PMC2611987  PMID: 19014560
5.  A test of financial incentives to improve warfarin adherence 
Sub-optimal adherence to warfarin places millions of patients at risk for stroke and bleeding complications each year. Novel methods are needed to improve adherence for warfarin. We conducted two pilot studies to determine whether a lottery-based daily financial incentive is feasible and improves warfarin adherence and anticoagulation control.
Volunteers from the University of Pennsylvania Anticoagulation Management Center who had taken warfarin for at least 3 months participated in either a pilot study with a lottery with a daily expected value of $5 (N = 10) or a daily expected value of $3 (N = 10). All subjects received use of an Informedix Med-eMonitor™ System with a daily reminder feature. If subjects opened up their pill compartments appropriately, they were entered into a daily lottery with a 1 in 5 chance of winning $10 and a 1 in 100 chance of winning $100 (pilot 1) or a 1 in 10 chance of winning $10 and a 1 in 100 chance of winning $100 (pilot 2). The primary study outcome was proportion of incorrect warfarin doses. The secondary outcome was proportion of INR measurements not within therapeutic range. Within-subject pre-post comparisons were done of INR measurements with comparisons with either historic means or within-subject comparisons of incorrect warfarin doses.
In the first pilot, the percent of out-of-range INRs decreased from 35.0% to 12.2% during the intervention, before increasing to 42% post-intervention. The mean proportion of incorrect pills taken during the intervention was 2.3% incorrect pills, compared with a historic mean of 22% incorrect pill taking in this clinic population. Among the five subjects who also had MEMS cap adherence data from warfarin use in our prior study, mean incorrect pill taking decreased from 26% pre-pilot to 2.8% in the pilot. In the second pilot, the time out of INR range decreased from 65.0% to 40.4%, with the proportion of mean incorrect pill taking dropping to 1.6%.
A daily lottery-based financial incentive demonstrated the potential for significant improvements in missed doses of warfarin and time out of INR range. Further testing should be done of this approach to determine its effectiveness and potential application to both warfarin and other chronic medications.
PMCID: PMC2635367  PMID: 19102784
6.  Use of reminders for preventive procedures in family medicine. 
OBJECTIVE: To compare the effectiveness of three computerized reminder systems in the delivery of five preventive procedures in family practice. DESIGN: Prospective, randomized, controlled study. SETTING: Ottawa Civic Hospital Family Medicine Centre. PARTICIPANTS: Of 8502 patients 15 years of age or more who were not in a hospital or institution 5883 were randomly assigned, by family, to a control group, a physician reminder group (passive) or a telephone or letter reminder group (active). The remaining 2619 patients were not included in the randomized portion of the study but were monitored. INTERVENTION: During 1 year the patients in the active reminder groups received a telephone call or letter reminding them of any overdue preventive procedures; for those in the passive reminder group the physician was reminded at an office visit to provide any overdue service. OUTCOME MEASURE: Rates of completion of the preventive procedures required. MAIN RESULTS: All three reminder systems significantly improved the delivery of preventive services (p less than 0.001). The procedure completion rates were 42.0% in the letter reminder group, 42.0% in the telephone reminder group, 33.7% in the physician reminder group and 14.1% in the randomized control group. The use of a letter was more cost-effective than the telephone system, but the physician reminder system was the most cost-effective. CONCLUSION: Computerized reminder systems do improve the delivery of preventive services in family practice.
PMCID: PMC1335900  PMID: 1913409
7.  A computer-generated reminder system improves physician compliance with diabetes preventive care guidelines. 
Computerized reminder systems have been shown to be effective in improving physician compliance with preventive services guidelines. Very little has been published about the use of computerized reminders for preventive care in diabetes. We implemented a computer-generated reminder system for diabetes care guidelines in a randomized controlled study in the outpatient clinics of 35 internal medicine residents at the University of Utah and Salt Lake Veterans Affairs Hospitals. After a six month study period, compliance with the recommended care significantly improved in both the intervention group that received patient-specific reminders about the guidelines (38.0% at baseline, 54.9% at follow-up) and the control group that received a nonspecific report (34.6% at baseline, 51.0% at follow-up). There was no significant difference between the two groups. Both clinic sites showed similar improvement over baseline levels of compliance. Residents who completed encounter forms used by the system showed a significantly greater improvement in compliance than those who did not complete encounter forms (19.7% vs. 7.6%, p = 0.006). The improvements in guideline compliance were seen in all areas of diabetes preventive care studied, and significant improvements were seen with recommended items from the medical history, physical exam, laboratory testing, referrals, and patient education. The use of encounter forms by the providers significantly improved documented compliance with the guidelines in almost all categories of preventive care. These results suggest that computerized reminder systems improve compliance with recommended care more by facilitating the documentation of clinical findings and the ordering of recommended procedures than by providing the clinician with patient-specific information about guideline compliance status. Further study is needed to understand the implications of these findings to the development of future computerized reminder systems for chronic diseases such as diabetes.
PMCID: PMC2579172  PMID: 8563365
8.  The effect of computer-based reminders on the management of hospitalized patients with worsening renal function. 
We performed a prospective time-series study to determine whether computerized reminders to physicians about rising creatinine levels in hospitalized patients receiving nephrotoxic and renally excreted medications led to more rapid adjustment or discontinuation of those medications, and to evaluate physician acceptance of computerized reminders. Laboratory data were followed on 10,076 patients over 13,703 admissions generating 1104 events of rising creatinine levels during treatment with nephrotoxic or renally excreted medications. During the intervention period, medications were adjusted or discontinued an average of 21.1 hours sooner (p less than 0.0001) after such an event occurred when compared with the control period. This effect of the reminders was strongest for patients receiving renally excreted and mildly nephrotoxic medications. Of physicians who responded to a computerized survey, 53% said that the reminders had been helpful in the care of their patients, while 31% felt that the reminders were annoying. Seventy-three percent wished to continue receiving computerized reminders. We conclude that computerized reminders are well-accepted in our hospital and have a strong effect on physician behavior.
PMCID: PMC2247489  PMID: 1807605
9.  Pharmacokinetic and pharmacodynamic variability of fluindione in octogenarians 
In the PREPA observational study, we investigated the factors influencing pharmacokinetic and pharmacodynamic variability in the response to fluindione, an oral anticoagulant drug, in a general population of octogenarians inpatients.
Measurements of fluindione concentrations and INR (International Normalised Ratio) were obtained from 131 inpatients initiating fluindione treatment. Treatment was adjusted according to routine clinical practice. The data was analysed using non-linear mixed effect models, and the parameters were estimated using MONOLIX 3.2.
The pharmacokinetics of fluindione was monocompartmental, while the evolution of INR was modelled according to a turnover model (inhibition of vitamin K recycling). Interindividual variability was very large. Clearance decreased with age and with prior administration of cordarone. Patients who underwent surgery before the study had lower IC50, leading to an increased sensitivity to fluindione.
Pharmacokinetic exposure is substantially increased in elderly patients, warranting a lower dose of fluindione.
PMCID: PMC3789273  PMID: 22472992
Aged; Aged, 80 and over; Anticoagulants; pharmacokinetics; pharmacology; Female; Humans; International Normalized Ratio; Male; Phenindione; analogs & derivatives; pharmacokinetics; pharmacology; fluindione; antivitamin K; oral anticoagulant; elderly; pharmacokinetics; pharmacodynamics; International Normalised Ratio (INR)
10.  Patients' perspectives on self-testing of oral anticoagulation therapy: Content analysis of patients' internet blogs 
Patients on oral anticoagulant therapy (OAT) require regular testing of the prothrombin time (PT) and the international normalised ratio (INR) to monitor their blood coagulation level to avoid complications of either over or under coagulation. PT/INR can be tested by a healthcare professional or by the patient. The latter mode of the testing is known as patient self-testing or home testing. The objective of this study was to elicit patients' perspectives and experiences regarding PT/INR self-testing using portable coagulometer devices.
Internet blog text mining was used to collect 246 blog postings by 108 patients, mainly from the USA and the UK. The content of these qualitative data were analysed using XSight and NVivo software packages.
The key themes in relation to self-testing of OAT identified were as follows: Patient benefits reported were time saved, personal control, choice, travel reduction, cheaper testing, and peace of mind. Equipment issues included high costs, reliability, quality, and learning how to use the device. PT/INR issues focused on the frequency of testing, INR fluctuations and individual target (therapeutic) INR level. Other themes noted were INR testing at laboratories, the interactions with healthcare professionals in managing and testing OAT and insurance companies' involvement in acquiring the self-testing equipment. Social issues included the pain and stress of taking and testing for OAT.
Patients' blogs on PT/INR testing provide insightful information that can help in understanding the nature of the experiences and perspectives of patients on self-testing of OAT. The themes identified in this paper highlight the substantial complexities involved in self-testing programmes in the healthcare system. Thus, the issues elicited in this study are very valuable for all stakeholders involved in developing effective self-testing strategies in healthcare that are gaining considerable current momentum particularly for patients with chronic illness.
PMCID: PMC3045880  PMID: 21291542
11.  Effect of an interactive voice response system on oral anticoagulant management 
Monitoring oral anticoagulants is logistically challenging for both patients and medical staff. We evaluated the effect of adding an interactive voice response system to computerized decision support for oral anticoagulant management.
We developed an interactive voice response system to communicate to patients the results of international normalized ratio testing and their dosage schedules for anticoagulation therapy. The system also reminded patients of upcoming and missed appointments for blood tests. We recruited patients whose anticoagulation control was stable after at least 3 months of warfarin therapy. We prospectively examined clinical data and outcomes for these patients for an intervention period of at least 3 months. We also collected retrospective data for each patient for the 3 months before study enrolment.
We recruited 226 patients between Nov. 23, 2006, and Aug. 1, 2007. The mean duration of the intervention period (prospective data collection) was 4.2 months. Anticoagulation control was similar for the periods during and preceding the intervention (mean time within the therapeutic range 80.3%, 95% confidence interval [CI] 77.5% to 83.1% v. 79.9%, 95% CI 77.3% to 82.6%). The interactive voice response system delivered 1211 (77.8%) of 1557 scheduled dosage messages, with no further input required from clinic staff. The most common reason for clinic staff having to deliver the remaining messages (accounting for 143 [9.2%] of all messages) was an international normalized ratio that was excessively high or low, (i.e., 0.5 or more outside the therapeutic range). When given the option, 76.6% of patients (164/214) chose to continue with the interactive voice response system for management of their anticoagulation after the study was completed. The system reduced staff workload for monitoring anticoagulation therapy by 48 min/wk, a 33% reduction from the baseline of 2.4 hours.
Interactive voice response systems have a potential role in improving the monitoring of patients taking oral anticoagulants. Further work is required to determine the generalizability and cost-effectiveness of these results.
PMCID: PMC2670905  PMID: 19398739
12.  Comparing the quality of oral anticoagulant management by anticoagulation clinics and by family physicians: a randomized controlled trial 
There is growing evidence that better outcomes are achieved when anticoagulation is managed by anticoagulation clinics rather than by family physicians. We carried out a randomized controlled trial to evaluate these 2 models of anticoagulant care.
We randomly allocated patients who were expected to require warfarin sodium for 3 months either to anticoagulation clinics located in 3 Canadian tertiary hospitals or to their family physician practices. We evaluated the quality of oral anticoagulant management by comparing the proportion of time that the international normalized ratio (INR) of patients receiving warfarin sodium was within the target therapeutic range ± 0.2 INR units (expanded therapeutic range) while they were managed in anticoagulation clinics as opposed to family physicians' care over 3 months. We measured the rates of thromboembolic and major hemorrhagic events and patient satisfaction in the 2 groups.
Of the 221 patients enrolled, 112 were randomly assigned to anticoagulation clinics and 109 to family physicians. The INR values of patients who were managed by anticoagulation clinics were within the expanded therapeutic range 82% of the time versus 76% of the time for those managed by family physicians (p = 0.034). High-risk INR values (defined as being < 1.5 or > 5.0) were more commonly observed in patients managed by family physicians (40%) than in patients managed by anticoagulation clinics (30%, p = 0.005). More INR measurements were performed by family physicians than by anticoagulation clinics (13 v. 11, p = 0.001). Major bleeding events (2 [2%] v. 1 [1%]), thromboembolic events (1 [1%] v. 2 [2%]) and deaths (5 [4%] v. 6 [6%]) occurred at a similar frequency in the anticoagulation clinic and family physician groups respectively. Of the 170 (77%) patients who completed the patient satisfaction questionnaire, more were satisfied when their anticoagulant management was managed through anticoagulation clinics than by their family physicians (p = 0.001).
Anticoagulation clinics provided better oral anticoagulant management than family physicians, but the differences were relatively modest.
PMCID: PMC180652  PMID: 12925422
13.  Comparison of three methods of recalling patients for influenza vaccination. 
Despite recommendations supporting annual influenza vaccination for people aged 65 years or older, vaccination rates remain low. Several studies have evaluated the effect of sending mailed reminders, but few have compared alternative ways of reminding patients to receive the vaccine. In a randomized trial of 939 patients aged 65 years or older in four family practices carried out between Oct. 23 and Dec. 31, 1984, we compared three ways of reminding elderly patients to receive the vaccine: personal reminder by the physician, telephone reminder by the nurse and reminder by letter. The vaccination rates for the three groups were 22.9%, 37% and 35.1% respectively. No reminder was issued to a control group, and the rate was 9.8%. Some patients could not be reached by telephone, and some did not see the physician during the specified time. Among the patients whom the nurse actually contacted, the vaccination rate was 43.5%; the rate for patients whom the doctor actually saw was 45.1%. Overall, a telephone reminder by the nurse was the most effective method, and at an hourly salary of $16 or less this method would also be the most cost-effective. The reminders used in this study were automatically generated from a computerized medical record system. The study shows how a computerized system can be used to identify patients for whom preventive procedures are due.
PMCID: PMC1491283  PMID: 3093045
14.  Home prophylactic warfarin anticoagulation program after hip and knee arthroplasty  
Canadian Journal of Surgery  1999;42(5):360-362.
To determine the efficiency of a program designed to maintain prophylactic oral anticoagulation within a target range for 6 weeks after hip and knee arthroplasty.
A prospective continuous quality improvement indicator.
A tertiary care university hospital.
Patients who underwent hip and knee arthroplasty and had no indications for routine anticoagulation other than postoperative thromboembolism prophylaxis.
An outpatient warfarin prophylaxis program, which included an information letter given to the patient, Home Care coordinated community laboratory services, communication with and anticoagulant dosage adjustment by the patient’s personal family physician.
Outcome measures
The proportion of international normalized ratio (INR) values within, below and above the target range of 2.0 to 3.0.
Sixty-two patients were enrolled over a 3-month period. On the day of hospital discharge, 64% of patients had INR values that were within the target range, 31% were below and 5% were above. After hospital discharge, 42% of the INR values were within the target range, 48% were below and 10% were above.
Despite a program designed to address patient information, physician communication and laboratory testing, tight control of home INR values could not be achieved with the existing resources of Home Care and family physicians.
PMCID: PMC3788901  PMID: 10526520
15.  Evaluation of a pharmacist-managed anticoagulation clinic: Improving patient care 
Open Medicine  2009;3(1):e16-e21.
Anticoagulation management services (AMSs) are widely used for anticoagulation management in many countries. Our AMS is a pharmacist-run ambulatory clinic with a physician advisory committee that manages patients referred with complicated anticoagulation histories. This paper assesses the adequacy of anticoagulation, rates of anticoagulant-related events and associated health care resource utilization for patients before and after referral to our AMS.
Consecutive patients referred to the AMS with 4 months of prior anticoagulation management who also had anticoagulation management for 4 months within the AMS were included in the evaluation. The primary endpoint was adequacy of anticoagulation (target international normalized ratio [INR] ± 0.5). Secondary outcomes included adverse events requiring an emergency department (ED) visit or hospital stay. These were classified by International Classification of Diseases (ICD) codes as thromboembolic, hemorrhagic, or non-anticoagulant related. Health care system resource consumption data were collected as number of hours spent in an ED and hospitalization costs.
A total of 125 patients were included: 57.6% were male, with a mean age of 62.9 (standard deviation [SD]) ± 15.0 years. Indications for warfarin therapy were atrial fibrillation (40.0%), mechanical valve replacement (24.0%) and venous thromboembolism (19.2%). The adequacy of anticoagulant control was significantly greater during AMS care compared with the period before referral; patients were in the target INR range 66.5% versus 48.8% of the time, respectively (95% confidence interval [CI] 13.4%–22.0%; p < 0.0001). The relative risk of a thromboembolic event before referral to AMS care was 17.6 (95% CI 6.0–51.9; p < 0.0001), while the relative risk of a hemorrhagic event before AMS care was 1.6 (95% CI 0.7–3.7; p = 0.25). During AMS care, savings included 572 hours in the ED and Cdn$122,145.40 in hospitalization costs.
A pharmacist-directed, physician-supported AMS program achieved significantly better INR control and reduced rates of thromboembolic complications compared with standard care. Resource utilization was substantially reduced during AMS care.
PMCID: PMC2765765  PMID: 19946388
16.  Oral anticoagulation in a pediatric hospital: impact of a quality improvement initiative on warfarin management strategies 
Quality & Safety in Health Care  2006;15(4):240-243.
There are potential risks associated with the use of warfarin in children, particularly as the dosing requirements may decrease as patients get older.
Our facility is a 715‐bed freestanding pediatric tertiary care center with a large cardiac surgery center. A significant number of patients receive warfarin for treatment or prophylaxis of thromboembolic events while in hospital.
Key measures for improvement
Initial dose of warfarin and time taken to achieve goal therapeutic international normalized ratio (INR).
Strategies for change
The intervention included: (1) revision of hospital drug formulary so that warfarin dosing was in accordance with the most recent guidelines; (2) warfarin administration restricted to one time of the day (12.00 noon); (3) target therapeutic INR level documented with each warfarin order; and (4) pharmacy computer system mandated that the pharmacist confirmed the target INR, documented the most current INR, and compared the dose with the formulary guidelines. If the warfarin dose was not in accordance with the formulary guidelines, the pharmacist contacted the physician and made dosing recommendations according to the guidelines.
Effects of change
The number of patients with supratherapeutic INR values during the hospital admission was decreased by more than 50% and goal INR values were documented more frequently in the medical record. There was also an increase in subtherapeutic INR values. The intervention had no effect on the time taken to achieve the goal therapeutic INR.
Lessons learned
Instituting changes in a number of aspects of anticoagulation management and incorporating an intensive educational effort across a breadth of healthcare providers can improve anticoagulation management with warfarin in challenging patient populations such as children. Similar methods could possibly improve anticoagulation with other agents such as unfractionated heparin or low molecular weight heparin.
PMCID: PMC2564007  PMID: 16885247
warfarin; children; quality improvement; anticoagulation
17.  The effect of reminder systems on patients’ adherence to treatment 
Patient adherence is an important component of the treatment of chronic disease. An understanding of patient adherence and its modulating factors is necessary to correctly interpret treatment efficacy and barriers to therapeutic success.
This meta-analysis aims to systematically review published randomized controlled trials of reminder interventions to assist patient adherence to prescribed medications.
A Medline search was performed for randomized controlled trials published between 1968 and June 2011, which studied the effect of reminder-based interventions on adherence to self-administered daily medications.
Eleven published randomized controlled trials were found between 1999 and 2009 which measured adherence to a daily medication in a group receiving reminder interventions compared to controls receiving no reminders. Medication adherence was measured as the number of doses taken compared to the number prescribed within a set period of time. Meta- analysis showed a statistically significant increase in adherence in groups receiving a reminder intervention compared to controls (66.61% versus 54.71%, 95% CI for mean: 0.8% to 22.4%). Self-reported and electronically monitored adherence rates did not significantly differ (68.04% versus 63.67%, P = 1.0). Eight of eleven studies showed a statistically significant increase in adherence for at least one of the reminder group arms compared to the control groups receiving no reminder intervention.
The data are limited by imperfect measures of adherence due to variability in data collection methods. It is also likely that concomitant educational efforts in the study populations, such as instructions regarding proper administration and importance of correct dosing schedules, contributed to improved patient adherence, both in reminder and control arms. The search strategy could have missed relevant studies which were categorized by disease rather than adherence.
Reminder-based interventions may improve adherence to daily medications. However, the interventions used in these studies, which included reminder phone calls, text messages, pagers, interactive voice response systems, videotelephone calls, and programmed electronic audiovisual reminder devices, are impractical for widespread implementation, and their efficacy may be optimized when combined with alternative adherence-modifying strategies. More practical reminder-based interventions should be assessed to determine their value in improving patient adherence and treatment outcomes.
PMCID: PMC3287416  PMID: 22379363
patient adherence; medication reminders; treatment compliance
18.  The effectiveness of interventions using electronic reminders to improve adherence to chronic medication: a systematic review of the literature 
Many patients experience difficulties in adhering to long-term treatment. Although patients' reasons for not being adherent are diverse, one of the most commonly reported barriers is forgetfulness. Reminding patients to take their medication may provide a solution. Electronic reminders (automatically sent reminders without personal contact between the healthcare provider and patient) are now increasingly being used in the effort to improve adherence.
To examine the effectiveness of interventions using electronic reminders in improving patients' adherence to chronic medication.
A comprehensive literature search was conducted in PubMed, Embase, PsycINFO, CINAHL and Cochrane Central Register of Controlled Trials. Electronic searches were supplemented by manual searching of reference lists and reviews. Two reviewers independently screened all citations. Full text was obtained from selected citations and screened for final inclusion. The methodological quality of studies was assessed.
Thirteen studies met the inclusion criteria. Four studies evaluated short message service (SMS) reminders, seven audiovisual reminders from electronic reminder devices (ERD), and two pager messages. Best evidence synthesis revealed evidence for the effectiveness of electronic reminders, provided by eight (four high, four low quality) studies showing significant effects on patients' adherence, seven of which measured short-term effects (follow-up period <6 months). Improved adherence was found in all but one study using SMS reminders, four studies using ERD and one pager intervention. In addition, one high quality study using an ERD found subgroup effects.
This review provides evidence for the short-term effectiveness of electronic reminders, especially SMS reminders. However, long-term effects remain unclear.
PMCID: PMC3422829  PMID: 22534082
Chronic medication; electronic reminders; interventions; medication adherence; systematic review
19.  Improving medication adherence in diabetes type 2 patients through Real Time Medication Monitoring: a Randomised Controlled Trial to evaluate the effect of monitoring patients' medication use combined with short message service (SMS) reminders 
Innovative approaches are needed to support patients' adherence to drug therapy. The Real Time Medication Monitoring (RTMM) system offers real time monitoring of patients' medication use combined with short message service (SMS) reminders if patients forget to take their medication. This combination of monitoring and tailored reminders provides opportunities to improve adherence. This article describes the design of an intervention study aimed at evaluating the effect of RTMM on adherence to oral antidiabetics.
Randomised Controlled Trial (RCT) with two intervention arms and one control arm involving diabetes type 2 patients with suboptimal levels of adherence to oral antidiabetics (less than 80% based on pharmacy refill data). Patients in the first intervention arm use RTMM including SMS reminders and a personal webpage where they can monitor their medication use. Patients in the second intervention arm use RTMM without SMS reminders or webpage access. Patients in the control arm are not exposed to any intervention. Patients are randomly assigned to one of the three arms. The intervention lasts for six months. Pharmacy refill data of all patients are available from 11 months before, until 11 months after the start of the intervention. Primary outcome measure is adherence to oral antidiabetics calculated from: 1) data collected with RTMM, as a percentage of medication taken as prescribed, and as percentage of medication taken within the correct time interval, 2) refill data, taking the number of days for which oral antidiabetics are dispensed during the study period divided by the total number of days of the study period. Differences in adherence between the intervention groups and control group are studied using refill data. Differences in adherence between the two intervention groups are studied using RTMM data.
The intervention described in this article consists of providing RTMM to patients with suboptimal adherence levels. This system combines real time monitoring of medication use with SMS reminders if medication is forgotten. If RTMM proves to be effective, it can be considered for use in various patient populations to support patients with their medication use and improve their adherence.
Trial registration
Netherlands Trial Register NTR1882
PMCID: PMC3024217  PMID: 21219596
20.  Comparative evaluation of warfarin utilisation in two primary healthcare clinics in the Cape Town area 
Although warfarin remains the anticoagulant drug of choice in a wide range of patients, its narrow therapeutic window makes patients susceptible to a high risk of bleeding complications or failure to prevent clotting. This has necessitated therapeutic monitoring in warfarinised patients. Factors that could be responsible for the fluctuating responses to warfarin vary from pharmacogenetic to concomitant morbidity, diet and medication. In order to assess the quality of management of warfarin treatment in a local primary-care setting, the current study evaluated warfarin utilisation and monitoring records in two hospitals with different patient groups.
A retrospective study was undertaken in the specialised warfarin clinics at Wesfleur and Gugulethu hospitals (Western Cape, South Africa) covering all warfarin-related therapy records over a 12-month period. Data extracted from the patients’ folders included age, gender, race, weight, address, concurrent chronic illnesses, treatment and medication, indication for warfarin and INR history.
A total of 119 patients’ folders were analysed. Attendance at the clinics reflects the demographics and racial distribution of the host location of the hospitals. While all the patients were maintained above the minimum international normalised ratio (INR) value of 2, about 50% had at least one record of INR above the cut-off value of 3.5. However, over a third of the patients (32.2%) had at least one record of INR greater than 3.5 in Gugulethu Hospital, compared to over half (58.3%) in Wesfleur Hospital.
In total, atrial fibrillation was the most common indication for warfarinisation while hypertension was the most common concurrent chronic condition in warfarinised patients. All patients who received quinolone antibiotics had INR values above the cut-off point of 3.5 within the same month of the initiation of antibiotic therapy, suggesting drug-induced warfarin potentiation. Other co-medications, including beta-lactam antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs) and anti-ulcer drugs appeare to alter warfarin responses as measured by recorded INR values.
The study found inter-individual variability in the response to warfarin therapy, which cut across racial classifications. It also confirms the possible influence of concomitant morbidity on patient response to anticoagulant therapy.
PMCID: PMC3736381  PMID: 23750346
warfarin; drug monitoring; international normalised ratio; anticoagulant; warfarinisation
21.  Dental extraction in patients on warfarin treatment 
Warfarin is one of the most common oral anticoagulants used to prevent thromboembolic episodes. The benefits of discontinuation of this drug before simple surgical procedures are not clear and this approach could be associated with complications. The aim of this study was to evaluate the risk of bleeding in a series of 35 patients (in cases where the international normalized ratio [INR] is less than 4) following simple tooth extraction without modification of the warfarin dose given to patients.
Thirty-five patients taking warfarin who had been referred to the Oral and Maxillofacial Department, College of Dentistry, King Saud University, for dental extractions were included in the study. Exclusion criteria included patients with an INR of ≥4 or with a history of liver disease or coagulopathies. No alteration was made in warfarin dose, and the CoaguChek System was used to identify the INR on the same day of dental extraction. Bleeding from the extraction site was evaluated and recorded immediately after extraction until the second day.
A total of 35 patients (16 women and 19 men) aged between 38 and 57 years (mean =48.7) were included in the present study. All patients underwent simple one-tooth extraction while undergoing warfarin treatment. Oozing, considered mild bleeding and which did not need intervention was seen in 88.6% of patients. Moderate bleeding occurred in 11.4% of all cases. The INR of the patients ranged from 2.00 to 3.50, with 77.2% of patients having INR between 2.0 and 2.5 on the day of extraction. No severe bleeding which needed hospital management was encountered after any of the extractions. The patients who suffered moderate bleeding were returned to the clinic where they received local treatment measures to control bleeding. Moderate bleeding occurred only in four patients, where three had INR between 3.1 and 3.5, and one with INR less than 3.
In the present study, we have shown that simple tooth extraction in patients on warfarin treatment can be performed safely without high risk of bleeding, providing that the INR is equal or less than 3.5 on the day of extraction. A close follow-up and monitoring of patients taking warfarin is mandatory after dental extraction.
PMCID: PMC4144934  PMID: 25170281
tooth extraction; bleeding; INR
22.  The DIAMIND study: postpartum SMS reminders to women who have had gestational diabetes mellitus to test for type 2 diabetes: a randomised controlled trial – study protocol 
Postpartum follow up of women who have been found to have gestational diabetes during pregnancy is essential because of the strong association of gestational diabetes with subsequent type 2 diabetes. Postal reminders have been shown to increase significantly attendance for oral glucose tolerance testing postpartum. It is possible that a short message service (text) reminder system may also be effective. This trial aims to assess whether a text message reminder system for women who have experienced gestational diabetes in their index pregnancy will increase attendance for oral glucose tolerance testing within six months after birth.
Design: Single centre (Women’s and Children’s Hospital, South Australia), parallel group randomised controlled trial.
Inclusion criteria: Women diagnosed with gestational diabetes in their index pregnancy (oral glucose tolerance test with fasting glucose ≥ 5.5 mmol/L and/or two hour glucose ≥ 7.8 mmol/L), with access to a mobile phone, whose capillary blood glucose profile measurements prior to postnatal discharge are all normal (fasting glucose < 6.0 mmol/L, postprandial glucoses < 8.0 mmol/L).
Exclusion criteria: Pregestational diabetes mellitus, triplet/higher order multiple birth or stillbirth in the index pregnancy, requirement for interpreter.
Trial entry and randomisation: Allocation to intervention will be undertaken using a telephone randomisation service (computer-generated random number sequence generation, with balanced variable blocks, and stratification by insulin requirement).
Study groups: Women in the intervention group will receive a text reminder to attend for an oral glucose tolerance test at 6 weeks postpartum, with further reminders at 3 months and 6 months if they do not respond to indicate test completion. Women in the control group will receive a single text message reminder at 6 months postpartum.
Blinding: Baseline data collection will be undertaken blinded. Blinding of participants and blinded collection of primary outcome data will not be possible for this study.
Primary study outcome: Attendance for the oral glucose tolerance test within 6 months postpartum.
Sample size: 276 subjects will be required to show an 18% absolute increase in the rate of attendance (α=0.05 two tailed, β=80%, 5% loss to follow up) from 37% to 55% in the intervention group.
Given the heightened risk of impaired glucose tolerance and type 2 diabetes in women who have had gestational diabetes, ensuring the highest possible rate of attendance for postpartum glucose tolerance testing, so that early diagnosis and intervention can occur, is important. A text message reminder system may prove to be an effective method for achieving improved attendance for such testing. This randomised controlled trial will assess whether such a system will increase rates of attendance for postpartum oral glucose tolerance testing in women who have experienced gestational diabetes.
Trial Registration
Australian New Zealand Clinical Trials Registry - ACTRN12612000621819
PMCID: PMC3626874  PMID: 23587090
Gestational diabetes mellitus; Reminder system; SMS text reminder; Randomised controlled trial; Postpartum care; Oral glucose tolerance test; Type 2 diabetes mellitus
23.  How Well Does the Target INR Level Maintain in Warfarin-Treated Patients with Non-ValvularAtrial Fibrillation? 
Yonsei Medical Journal  2009;50(1):83-88.
Although warfarin is an effective oral anticoagulation (OAC) drug to reduce the risk of thromboembolism in patients with non-valvular atrial fibrillation (NVAF), long term follow-up data are scarce to be certain whether the target INR level is maintained in warfarin-treated patients in Korea. The aim of this study was to evaluate how well INRs are maintained within the target range using a new index, INR stability (= 100 × number of INRs within target range/total number of INR measurements) which we made, and to find out any correlation between thromboembolic events and INR stability.
Materials and Methods
This study was an observational analysis of retrospectively collected data of 129 patients with NVAF from April 2000 to December 2005 at a single tertiary hospital. All patients were registered at the anticoagulation service.
The median duration of follow up was 2.03 years (interquartile range 1.35 - 2.96). During the follow-up period, 60.9 ± 14.9% of the INR were within the target INR range. INR stability was not significantly different between patients without and with stroke (61.2 ± 15.0% vs 53.3 ± 4.9%). Among the known factors affecting fluctuations of the INR value, the most frequent factor was noncompliance (41.8%).
The present study showed that it was not enough to maintain INR values within the target range in warfarin-treated patients with NVAF even at a tertiary hospital. Noncompliance is an important problem which interferes with maintaining target INR range.
PMCID: PMC2649856  PMID: 19259353
Anticoagulation; atrial fibrillation
24.  An Effective Computerized Reminder for Contact Isolation of Patients Colonized or Infected with Resistant Organisms 
To improve contact isolation rates among patients admitted to the hospital with a known history of infection with Methicillin-resistant Staphylococcus aureus (MRSA) and Vancomycin-resistant Enterococci (VRE).
A before and after interventional study implementing computerized reminders for contact isolation between February 25th of 2005 and February 28th of 2006. We measured rates of appropriate contact isolation, and time to isolation for the four month pre-intervention period, and the 12 month intervention period. We conducted a survey of ordering physicians at the midpoint of the intervention period.
Implementing a computerized reminder increased the rate of patients appropriately isolated from 33% to fully 89% (P < 0.0001). The median time to writing contact isolation orders decreased from 16.6 hours to 0.0 hours (P < 0.0001). Physicians accepted the order 80% of the time on the first or second presentation. 95% of physicians felt the reminder had no impact on workflow, or saved them time.
A human reviewed computerized reminder can achieve high rates of compliance with infection control recommendations for contact isolation, and dramatically reduce the time to orders being written upon admission.
PMCID: PMC2974622  PMID: 17398145
Clinical Decision Support Systems; Reminder Systems; Infection Control; Methicillin-resistance; Staphylococcus aureus; Vancomycin Resistance; Enterococcus
25.  e-Health, m-Health and healthier social media reform: the big scale view 
In the upcoming decade, digital platforms will be the backbone of a strategic revolution in the way medical services are provided, affecting both healthcare providers and patients. Digital-based patient-centered healthcare services allow patients to actively participate in managing their own care, in times of health as well as illness, using personally tailored interactive tools. Such empowerment is expected to increase patients’ willingness to adopt actions and lifestyles that promote health as well as improve follow-up and compliance with treatment in cases of chronic illness. Clalit Health Services (CHS) is the largest HMO in Israel and second largest world-wide. Through its 14 hospitals, 1300 primary and specialized clinics, and 650 pharmacies, CHS provides comprehensive medical care to the majority of Israel’s population (above 4 million members). CHS e-Health wing focuses on deepening patient involvement in managing health, through personalized digital interactive tools. Currently, CHS e-Health wing provides e-health services for 1.56 million unique patients monthly with 2.4 million interactions every month (August 2011). Successful implementation of e-Health solutions is not a sum of technology, innovation and health; rather it’s the expertise of tailoring knowledge and leadership capabilities in multidisciplinary areas: clinical, ethical, psychological, legal, comprehension of patient and medical team engagement etc. The Google Health case excellently demonstrates this point. On the other hand, our success with CHS is a demonstration that e-Health can be enrolled effectively and fast with huge benefits for both patients and medical teams, and with a robust business model.
CHS e-Health core components
They include:
1. The personal health record layer (what the patient can see) presents patients with their own medical history as well as the medical history of their preadult children, including diagnoses, allergies, vaccinations, laboratory results with interpretations in layman’s terms, medications with clear, straightforward explanations regarding dosing instructions, important side effects, contraindications, such as lactation etc., and other important medical information. All personal e-Health services require identification and authorization.
2. The personal knowledge layer (what the patient should know) presents patients with personally tailored recommendations for preventative medicine and health promotion. For example, diabetic patients are push notified regarding their yearly eye exam. The various health recommendations include: occult blood testing, mammography, lipid profile etc. Each recommendation contains textual, visual and interactive content components in order to promote engagement and motivate the patient to actually change his health behaviour.
3. The personal health services layer (what the patient can do) enables patients to schedule clinic visits, order chronic prescriptions, e-consult their physician via secured e-mail, set SMS medication reminders, e-consult a pharmacist regarding personal medications. Consultants’ answers are sent securely to the patients’ personal mobile device.
On December 2009 CHS launched secured, web based, synchronous medical consultation via video conference. Currently 11,780 e-visits are performed monthly (May 2011). The medical encounter includes e-prescription and referral capabilities which are biometrically signed by the physician. On December 2010 CHS launched a unique mobile health platform, which is one of the most comprehensive personal m-Health applications world-wide. An essential advantage of mobile devices is their potential to bridge the digital divide. Currently, CHS m-Health platform is used by more than 45,000 unique users, with 75,000 laboratory results views/month, 1100 m-consultations/month and 9000 physician visit scheduling/month.
4. The Bio-Sensing layer (what physiological data the patient can populate) includes diagnostic means that allow remote physical examination, bio-sensors that broadcast various physiological measurements, and smart homecare devices, such as e-Pill boxes that gives seniors, patients and their caregivers the ability to stay at home and live life to its fullest. Monitored data is automatically transmitted to the patient’s Personal Health Record and to relevant medical personnel.
The monitoring layer is embedded in the chronic disease management platform, and in the interactive health promotion and wellness platform. It includes tailoring of consumer-oriented medical devices and service provided by various professional personnel—physicians, nurses, pharmacists, dieticians and more.
5. The Social layer (what the patient can share). Social media networks triggered an essential change at the humanity ‘genome’ level, yet to be further defined in the upcoming years. Social media has huge potential in promoting health as it combines fun, simple yet extraordinary user experience, and bio-social-feedback. There are two major challenges in leveraging health care through social networks:
a. Our personal health information is the cornerstone for personalizing healthier lifestyle, disease management and preventative medicine. We naturally see our personal health data as a super-private territory. So, how do we bring the power of our private health information, currently locked within our Personal Health Record, into social media networks without offending basic privacy issues?
b. Disease management and preventive medicine are currently neither considered ‘cool’ nor ‘fun’ or ‘potentially highly viral’ activities; yet, health is a major issue of everybody’s life. It seems like we are missing a crucial element with a huge potential in health behavioural change—the Fun Theory. Social media platforms comprehends user experience tools that potentially could break current misconception, and engage people in the daily task of taking better care of themselves.
CHS e-Health innovation team characterized several break-through applications in this unexplored territory within social media networks, fusing personal health and social media platforms without offending privacy. One of the most crucial issues regarding adoption of e-health and m-health platforms is change management. Being a ‘hot’ innovative ‘gadget’ is far from sufficient for changing health behaviours at the individual and population levels.
CHS health behaviour change management methodology includes 4 core elements:
1. Engaging two completely different populations: patients, and medical teams. e-Health applications must present true added value for both medical teams and patients, engaging them through understanding and assimilating “what’s really in it for me”. Medical teams are further subdivided into physicians, nurses, pharmacists and administrative personnel—each with their own driving incentive. Resistance to change is an obstacle in many fields but it is particularly true in the conservative health industry. To successfully manage a large scale persuasive process, we treat intra-organizational human resources as “Change Agents”. Harnessing the persuasive power of ~40,000 employees requires engaging them as the primary target group. Successful recruitment has the potential of converting each patient-medical team interaction into an exposure opportunity to the new era of participatory medicine via e-health and m-health channels.
2. Implementation waves: every group of digital health products that are released at the same time are seen as one project. Each implementation wave leverages the focus of the organization and target populations to a defined time span. There are three major and three minor implementation waves a year.
3. Change-Support Arrow: a structured infrastructure for every implementation wave. The sub-stages in this strategy include:
Cross organizational mapping and identification of early adopters and stakeholders relevant to the implementation wave
Mapping positive or negative perceptions and designing specific marketing approaches for the distinct target groups
Intra and extra organizational marketing
Conducting intensive training and presentation sessions for groups of implementers
Running conflict-prevention activities, such as advanced tackling of potential union resistance
Training change-agents with resistance-management behavioural techniques, focused intervention for specific incidents and for key opinion leaders
Extensive presence in the clinics during the launch period, etc.
The entire process is monitored and managed continuously by a review team.
4. Closing Phase: each wave is analyzed and a “lessons-learned” session concludes the changes required in the modus operandi of the e-health project team.
PMCID: PMC3571141
e-Health; mobile health; personal health record; online visit; patient empowerment; knowledge prescription

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