**4. Results of the platform**

Projects supported by the PITES platform since 2004 are described below. The list is not exhaustive. Those that have been considered as of greater interest have been included. From 2009 the platform has been open to other Spanish research groups.

### **4.1. Finalized projects**

**•** Impact of Patient–General Practitioner Short-Messages-Based Interaction on the Control of Hypertension in a Follow-up Service for Low-to-Medium Risk Hypertensive Patients: A Randomized Controlled Trial. (FIS 01/0915. SEP 1201/02. AIRMED II Program). [54]

– Main objective. To evaluate a telemedicine system for Primary Attention; improve the control and monitoring of arterial hypertension. Secondary objectives: Measure its effect on perceived health and anxiety.

– Type of study. Multicenter randomized controlled trial. 285 patients were enrolled by 38 GPs from 21 health centers in four different health areas in Madrid, Spain. October 2004-June 2006. Intervention period, 6 months.

– Description intervention. The coordination office set up appointments with the patients of both the TmG and the CG for training in self-blood pressure monitoring (SBPM) and the use of the digital sphygmomanometer (both groups) and the telephone (only TmG). During the six-month follow-up period, the TmG patients sent their mean self-measured SBP (sSBP) and DBP (sDBP), based on three measurements made at 3-min intervals under fasting conditions in the morning and at night, four times a week (Monday and Thursday, morning and night), and their pulse rate and weight once a week. During each WAP session, they had the option of responding to a simple questionnaire. At some later moment, with no obligation imposed by the protocol in terms of frequency of access to the CS, the GPs accessed the data sent by their patients via the Web. According to his or her own criteria, the GP could send an SMS regarding any related issue to the patient's phone. The CG patients followed the same SBPM protocol, with the exception that the results were recorded on paper in a data collection notebook; they sent no data to the CS, and thus, had no interaction with their GPs. They continued to make their scheduled visits to their GPs at their corresponding center, as they had done prior to the study.

rest of data facilitating to make information anonym. For security reasons this service is not accessible from the outside of the platform so that its possible clients may only be its running

Anonymisation service: this service enables to make anonym clinical information to be used in secondary uses such as research or statistics. This service accepts and returns extracts compliant with the standard reference model, codified in XML. Received extracts are analyzed to suppress the identification of the patient including demographic information codified in class IDENTIFIED\_ENTITY of the reference model, even though the year of birthday (not including day and month) and the sex of the patient may be preserved for statistical purposes. To do so, a new randomized identifier is assigned and substituted in the extract. This service makes use of the demographic service in order to maintain a record of the identifiers in use so that if further information about the same patient arrives its identifier can be assigned and the health information repository remains coherent. For this reason it is possible to install this service and the demographic service in the client side so that the information about the person does not leave the organization where it was generated and the clinical information is

Projects supported by the PITES platform since 2004 are described below. The list is not exhaustive. Those that have been considered as of greater interest have been included. From

**•** Impact of Patient–General Practitioner Short-Messages-Based Interaction on the Control of Hypertension in a Follow-up Service for Low-to-Medium Risk Hypertensive Patients: A Randomized Controlled Trial. (FIS 01/0915. SEP 1201/02. AIRMED II Program). [54]

– Main objective. To evaluate a telemedicine system for Primary Attention; improve the control and monitoring of arterial hypertension. Secondary objectives: Measure its effect on perceived

– Type of study. Multicenter randomized controlled trial. 285 patients were enrolled by 38 GPs from 21 health centers in four different health areas in Madrid, Spain. October 2004-June 2006.

– Description intervention. The coordination office set up appointments with the patients of both the TmG and the CG for training in self-blood pressure monitoring (SBPM) and the use of the digital sphygmomanometer (both groups) and the telephone (only TmG). During the six-month follow-up period, the TmG patients sent their mean self-measured SBP (sSBP) and DBP (sDBP), based on three measurements made at 3-min intervals under fasting conditions in the morning and at night, four times a week (Monday and Thursday, morning and night), and their pulse rate and weight once a week. During each WAP session, they had the option

2009 the platform has been open to other Spanish research groups.

applications or other supplied services.

200 Telemedicine

presented anonym to the outside world.

**4. Results of the platform**

**4.1. Finalized projects**

health and anxiety.

Intervention period, 6 months.

– Study variables. The main outcome measure, referred to by us as the degree of hypertension control, was the percentage of patients who were not optimally controlled at the time of the final visit. Optimal control was defined as a mean of three arterial pressure determinations carried out by a professional during the final visit, resulting in pSBP ≤ 140 mmHg and pDBP ≤ 90 mmHg. The secondary outcome measures were: 1) the changes in pSBP and pDBP between the initial and final visits measured in the office of the GP; 2) the changes in the mean selfmeasured sSBP, sDBP, and HR throughout the intervention period; 3) the changes in the dimensions of the brief profiles of the SF-36 Health Survey physical component summary (PCS) and mental component summary (MCS) and in the state anxiety (SA) and trait anxiety (TA), according to the State–Trait Anxiety Inventory (STAI); and 4) the number of consultations and hospital admissions in the two groups.

– Results. A) Degree of hypertension control. The number of patients exhibiting poor control at the final visit, was the case in 31.7% of the patients in the TmG and in 35.7% of those in the CG, (difference: 4.0%, 95% CI: −7.0% to 14.9%) there being no significant difference (p = 0.47). B) Change in hypertension during follow-up. In the comparison of the measurements carried out by the GPs at the initial and final visits, the TmG presented a decrease in pSBP of 15.5 mmHg and a decrease in pDBP of 9.6 mmHg, while in the CG, the pSBP decreased by 11.9 mmHg and the pDBP by 4.4 mmHg, decreases that did not differ significantly (pSBP: p=0.13; pDBP: p=0.40). The mean values for self-measured sSBP, sDBP, and HR (TmG: 131.6, 78.7, 70.1; CG: 132.4, 78.0, 69.7) throughout the six-month period, calculated according to the area under the curve, were not significantly different between the two groups (sSBP: p = 0.52; sDBP: p = 0.50; and HR: p = 0.79).

– Comments. There are no significant differences between the two groups in terms of the degree of hypertension control, measured as the number of poorly controlled patients at the final visit, given that the intention to treat analysis adds those that dropped out prior to the initial visit (TmG: n = 11; CG: n = 1) and those occurring during follow-up (TmG: n = 4; CG: n = 10) to the number of poorly controlled patients who underwent follow-up (TmG: n = 30; CG: n = 40). However self-blood pressure monitoring brings about improvements in hypertension control, given that the percentage of controlled patients in the final visit is greater in TmG. The reduction obtained in pSBP and pDBP in the TmG are consistent with the values reported by other authors, independent of the intervention selected.

**•** Evaluation of a Telemedicine-Based Service for the Follow-Up and Monitoring of Patients Treated With Oral Anticoagulant Therapy. (FIS 02/1156. SEP 1201/02. AIRMED II Program). [55]

– Main objective: To find out the acceptability and satisfaction of the patients who have a supervised system of self-controlled INR measurement, with home follow up by means of telemedicine based on mobile telephony within the ambit of Primary Attention. Secondary objectives: To determine the degree of control suitable for oral anticoagulant treatment achieved by patients, users of the system. To describe the eventual factors which condition a bad control. Clinically relevant possible accidents (hemorrhage and thrombosis) suffered by the patients in the study.

were six minor complications, four in the TmG and two in the CG, and three cases of throm‐ boembolism, one in the TmG and two in the CG. In the TmG, there was one hospital admission associated with OAT versus two due to other causes; in the CG, the incidence was three versus one, respectively. (C) Acceptability of the Change. With the exception of two patients, who received no help from the family and rejected the proposal for fear of being incapable of using the coagulometer and the cellular phone, all the patients were capable of self-testing and remained active in the project throughout the entire intervention period. The training sessions, held in groups of five patients, were approximately 2 h long, and were followed by a prereg‐ istered period of 1–2 weeks. In five cases, the INR measurement and WAP sessions were always carried out by a relative; in three cases, the patients did not even attend the training sessions,

PITES: Telemedicine and e-Health Innovation Platform

http://dx.doi.org/10.5772/57021

203

The patients in the TmG determined their INR on or around the date that had been indicated by the GP; 45.5% of the determinations were carried out on the designated day and 74.8% were carried out within 3 days, either before or after, of that date, indicating a high rate of adherence

The degree of compliance on the part of the GPs, measured as the time elapsed before they responded to a message from a patient, was very high; 48.5% of the total weekly dosage was

– Comments. The e-service exhibits highly positive features in terms of acceptability of the procedure, satisfaction, and quality of life, and reduces the number of visits to the healthcare

**•** Evaluation of a Telemedicine Service for the Secondary Prevention of Coronary Artery

– Main objective. To analyze the efficacy of a new telemonitoring system for the following up of patients with coronary heart disease (CHD), connecting patients, provided with selfmeasurement devices, and care managers through mobile phone messages over the Web, and integrating the monitoring of several cardiovascular risk factors (CRF), as a toll for secondary

– Type of study. A single-blind, randomized controlled, clinical trial. 203 acute coronary syndrome (ACS) survivors, was conducted at a hospital in Madrid, Spain. December 2007 -

– Description intervention. TmG patients were temporarily provided with an automatic sphygmomanometer, a glucose and lipid meter and a cellular phone, and support staff if needed, were taught to measure their blood pressure (BP), heart rate and weight (weekly), and glucose and lipids (monthly), and to send the results through their mobile phones following a structured questionnaire (WAP session). A cardiologist accessed the biological and clinical data via a secure Web application and, through this application, sent individualized short message service text messages with recommendations to the patients. At exit, subjects in the TmG completed an additional questionnaire to evaluate satisfaction with the program.

sent on the same day and 43.8% within 3 days of the reception of the message.

Disease. (TSI2005-02682. FIS PI05-1882. Programa MOBIS). [56]

January 2010. Intervention period: 12 months.

to the protocol, despite the freedom granted to the patients.

given their instability.

center.

prevention.

– Type of study. Quasi-experimental study, with two differentiated groups. 108 patients included in a Health Center in Pozuelo, Madrid, Spain. December 2004 -March 2006. Inter‐ vention period, 12 months

– Description intervention. The patients in the TmG were trained in the use of the coagulometer and the cellular phone by staff from the coordination office. At the beginning and end of the study, the patients in both the groups completed the quality of life questionnaire specific to anticoagulated patients designed by Sawicki; the SF-12 quality of life questionnaire for application in the general population; and the STAI to assess anxiety. The patients in the TmG measured their own INR every 3 weeks if they met the criteria for good control; otherwise, their GP proposed the date for the next determination and modification of the TWD. After each self-measurement, the patients sent their INR values and responded yes or no via a safe WAP session, to questions concerning another six clinical parameters, such as omission or duplication of doses, ingestion of new drugs, alcohol intake, changes in diet, fever, and intercurrent diseases, in order to define the causes of poor control.

– Study variables. Data on safety and the degree of control: a) Number of determinations made by each patient and their correlation with adequate INR control; b) number of determinations falling in and out of the target INR range, with the possible reasons for poor control; c) time during which each patient was in or out of the target INR range, measured using standard methods-–linear interpolation and in or out of range; and d) the incidence of adverse events associated with OAT (death, hemorrhagic complications, and thrombosis) in the two groups. Data concerning the acceptability of the change: a) The degree of compliance with the protocol in the TmG, measured both in the patients and the GPs and b) changes in the results of the three questionnaires provided at the beginning and end of the study.

– Results. (A) Degree of INR control. There were no significant differences between the two groups in terms of INR control. In all, 57.6% of the determinations in the TmG and 60.1% of those made in the CG were within this range. The patients in the TmG were in the target range (linear interpolation method) 65.4% of the time over a mean participation in the project of 329.4 days. In the CG, the patients were within the range 68.0% of the time over a mean duration of participation of 310.1 days. For the same variable measured by means of the in or out of range method, the rates were 66.6% in the TmG and 68.9% in the CG, over the same mean partici‐ pation time. The number of INR determinations within the target range, the number of days spent within the range according to the two conventional methods, and the distance, defined as the deviation of the INR determination from the center of the range for each patient, were also assessed. (B) Deaths, Complications, and Hospital Admissions. There were three deaths in each group; there were no major complications in the TmG and only one in the CG. There were six minor complications, four in the TmG and two in the CG, and three cases of throm‐ boembolism, one in the TmG and two in the CG. In the TmG, there was one hospital admission associated with OAT versus two due to other causes; in the CG, the incidence was three versus one, respectively. (C) Acceptability of the Change. With the exception of two patients, who received no help from the family and rejected the proposal for fear of being incapable of using the coagulometer and the cellular phone, all the patients were capable of self-testing and remained active in the project throughout the entire intervention period. The training sessions, held in groups of five patients, were approximately 2 h long, and were followed by a prereg‐ istered period of 1–2 weeks. In five cases, the INR measurement and WAP sessions were always carried out by a relative; in three cases, the patients did not even attend the training sessions, given their instability.

– Main objective: To find out the acceptability and satisfaction of the patients who have a supervised system of self-controlled INR measurement, with home follow up by means of telemedicine based on mobile telephony within the ambit of Primary Attention. Secondary objectives: To determine the degree of control suitable for oral anticoagulant treatment achieved by patients, users of the system. To describe the eventual factors which condition a bad control. Clinically relevant possible accidents (hemorrhage and thrombosis) suffered by

– Type of study. Quasi-experimental study, with two differentiated groups. 108 patients included in a Health Center in Pozuelo, Madrid, Spain. December 2004 -March 2006. Inter‐

– Description intervention. The patients in the TmG were trained in the use of the coagulometer and the cellular phone by staff from the coordination office. At the beginning and end of the study, the patients in both the groups completed the quality of life questionnaire specific to anticoagulated patients designed by Sawicki; the SF-12 quality of life questionnaire for application in the general population; and the STAI to assess anxiety. The patients in the TmG measured their own INR every 3 weeks if they met the criteria for good control; otherwise, their GP proposed the date for the next determination and modification of the TWD. After each self-measurement, the patients sent their INR values and responded yes or no via a safe WAP session, to questions concerning another six clinical parameters, such as omission or duplication of doses, ingestion of new drugs, alcohol intake, changes in diet, fever, and

– Study variables. Data on safety and the degree of control: a) Number of determinations made by each patient and their correlation with adequate INR control; b) number of determinations falling in and out of the target INR range, with the possible reasons for poor control; c) time during which each patient was in or out of the target INR range, measured using standard methods-–linear interpolation and in or out of range; and d) the incidence of adverse events associated with OAT (death, hemorrhagic complications, and thrombosis) in the two groups. Data concerning the acceptability of the change: a) The degree of compliance with the protocol in the TmG, measured both in the patients and the GPs and b) changes in the results of the

– Results. (A) Degree of INR control. There were no significant differences between the two groups in terms of INR control. In all, 57.6% of the determinations in the TmG and 60.1% of those made in the CG were within this range. The patients in the TmG were in the target range (linear interpolation method) 65.4% of the time over a mean participation in the project of 329.4 days. In the CG, the patients were within the range 68.0% of the time over a mean duration of participation of 310.1 days. For the same variable measured by means of the in or out of range method, the rates were 66.6% in the TmG and 68.9% in the CG, over the same mean partici‐ pation time. The number of INR determinations within the target range, the number of days spent within the range according to the two conventional methods, and the distance, defined as the deviation of the INR determination from the center of the range for each patient, were also assessed. (B) Deaths, Complications, and Hospital Admissions. There were three deaths in each group; there were no major complications in the TmG and only one in the CG. There

intercurrent diseases, in order to define the causes of poor control.

three questionnaires provided at the beginning and end of the study.

the patients in the study.

202 Telemedicine

vention period, 12 months

The patients in the TmG determined their INR on or around the date that had been indicated by the GP; 45.5% of the determinations were carried out on the designated day and 74.8% were carried out within 3 days, either before or after, of that date, indicating a high rate of adherence to the protocol, despite the freedom granted to the patients.

The degree of compliance on the part of the GPs, measured as the time elapsed before they responded to a message from a patient, was very high; 48.5% of the total weekly dosage was sent on the same day and 43.8% within 3 days of the reception of the message.

– Comments. The e-service exhibits highly positive features in terms of acceptability of the procedure, satisfaction, and quality of life, and reduces the number of visits to the healthcare center.

**•** Evaluation of a Telemedicine Service for the Secondary Prevention of Coronary Artery Disease. (TSI2005-02682. FIS PI05-1882. Programa MOBIS). [56]

– Main objective. To analyze the efficacy of a new telemonitoring system for the following up of patients with coronary heart disease (CHD), connecting patients, provided with selfmeasurement devices, and care managers through mobile phone messages over the Web, and integrating the monitoring of several cardiovascular risk factors (CRF), as a toll for secondary prevention.

– Type of study. A single-blind, randomized controlled, clinical trial. 203 acute coronary syndrome (ACS) survivors, was conducted at a hospital in Madrid, Spain. December 2007 - January 2010. Intervention period: 12 months.

– Description intervention. TmG patients were temporarily provided with an automatic sphygmomanometer, a glucose and lipid meter and a cellular phone, and support staff if needed, were taught to measure their blood pressure (BP), heart rate and weight (weekly), and glucose and lipids (monthly), and to send the results through their mobile phones following a structured questionnaire (WAP session). A cardiologist accessed the biological and clinical data via a secure Web application and, through this application, sent individualized short message service text messages with recommendations to the patients. At exit, subjects in the TmG completed an additional questionnaire to evaluate satisfaction with the program.

– Study variables. Outcome measures were resting BP, body mass index (BMI), smoking status, LDL-c, and glycated hemoglobin A1c (HbA1c), all measured at the initial and final visits for comparison. Their smoking status was determined by self-report and confirmed by a 1-step cotinine immunoassay in urine. The primary outcome was cardiovascular risk improvement (CRI), defined as the proportion of patients who achieve the goal of treatment in at least 1 CRF without exacerbation of any of the others. Treatment goals were as follows: (1) smoking cessation, (2) LDL-c less than 100 mg/dL, (3) BP lower than 140/90 mmHg, and (4) HbA1c less than 7%. Exacerbation of a CRF was defined as a 10% or more increase in BP, LDL-c, or HbA1c, with respect to initial levels. Secondary outcomes were: the proportion of patients achieving the treatment goal in each of the outcome measurements, quantitative changes in LDL-c, BP, BMI, and HbA1c (in diabetic patients), and changes in quality of life and level of anxiety.

were missed, due to the mobile phone being turned off. Family support of the TmG patients was analyzed at 4 different levels: never (58% of patients), first week only (10%), 1 month (7%),

PITES: Telemedicine and e-Health Innovation Platform

http://dx.doi.org/10.5772/57021

205

– Comments. A telemonitoring program, via mobile phone messages, appears to be useful for improving the risk profile in ACS survivors and can be an effective tool for secondary

**•** Control and monitoring of self-care plans in asthma by means of a telemedicine platform.

– Main objective. To evaluate the efficacy of a monitoring and self-care program for asthmatic patients based on telemedicine services. Secondary objectives: To evaluate the efficacy of the program as regards the adhesion to the self-care plans and to the adhesion to the monitoring of the FEM and FEV1. To evaluate the efficacy of the program as regards the clinical evolution

– Type of study. Quasi-experimental project with two differentiated groups: study and control. 37 patients of the Pneumology Unit of the Hospital Universitario Puerta de Hierro, Madrid,

– Description intervention. All of the patients have their FEM and FEV1 monitored daily (morning and evening) (volume expired in the first second), by means of a portable spirometer, their symptoms and the medication taken. Those of the CG entered their data manually on adhoc designed forms and acted in accordance with the guidelines given during the consultation. The patients of the TmG followed the same medical protocol, although unlike the control group, they had the permanent support of the telemedicine platform which sent the protocol information by means of a mobile telephone (spirometry through CSD-GSM transmission, and symptoms and actions by means of a WAP session on GPRS-GSM). The patients of the TmG immediately and automatically received an SMS message as a reply which included informa‐ tion on their current state and the recommended medication guidelines in accordance with their personalized plan. The doctor also has permanent access to the information sent and evolution of each TmG patient so that he or she could individually supervise the development

– Results. There we no significant differences as regards the monitoring of the FEV1 at home and in the consultations of the study group. Compliance with the self-care plans was 70% in more than half of the patients. Adherence to the self-treatment plans was greater in the study

– Comments. The tool that was designed to help in the decision-making process was highly

**•** AmIVital. Digital personal environment for health and wellbeing. (CENIT2007-1010). [58].

Other already carried out and finished projects are described briefly below

and always (25%).

of the self-care plans.

group (95.28%) than in the control (93.09%).

evaluated by both the patients and professionals.

prevention, especially for overweight patients.

(FIS 02/1391. SEP 1201/02. AIRMED II Program). [57].

of the asthma and quality of life of the patients with asthma.

Spain. October 2004 –May 2007. Intervention period, 12 months.

– Results. Four patients were lost in the followup (1.9%) and 5 died (2.5%), all in the CG. Seventeen patients left the study (8.4%), 12 in the TmG (11.8%) and 5 in the CG (4.9%) (RR = 2.38; 95% CI = 0.87-6.50; P =.08). Reasons for leaving the program in the TmG were stress associated with the use of the telemonitoring equipment in 3 patients, personal reasons in 7, and inability to handle the equipment in 2 patients; in the CG, all 5 attributed it to personal reasons.

Analysis on the basis of intention to treat showed that patients in the TmG were more likely (RR = 1.4; 95% CI = 1.1-1.7) to experience improvement in their CRF profile than patients in the CG (P =.010) at the end of 12 months. More TmG patients achieved the treatment goal in BP (62.1% vs 42.9%, P =.012; RR =1.4, 95% CI = 1.1-1.9) and in HbA1c among diabetic patients (86.4% vs 54.2%, P =.018; RR = 1.6; 95% CI = 1.1-2.4); there were no between-group differences for smoking cessation (80.7% vs 81.0%, P =.964; RR = 1.0; 95% CI = 0.9-1.1) or LDL-c (76.2% vs 76.6%, P =.948; RR = 1.0; 95% CI = 0.9-1.2).

Quantitative changes in continuous variables with comparison of the difference between the groups: Patients in the TmG showed significant changes in all variables with the exception of diastolic BP (DBP) (systolic BP [SBP], P =.0460; DBP, P =.237; LDL-c, P =.027; HbA1c, P =.001; BMI in overweight patients P =.003). In the CG, significant reductions were obtained in LDLc and DBP (SBP, P =.780; DBP, P =.001; LDL-c, P =.098; HbA1c, P =.239; BMI, P =.299). Body mass index diminished in the TmG and increased slightly in the CG. Triglyceride levels also decreased significantly in the TmG (P =.0001), but not in the CG (P =.435). No differences between-groups were found in physical activity (75% TmG vs 73% CG, P =.756) or medication adherence (99% in both groups, P =.980) both self-reported by patients. Nutritional habits were not explored. There were no significant differences between the scores obtained in SF-36 and State-Trait Anxiety Inventory tests at the initial visit in the 2 groups and changes were not significant between groups. At 12 months, the SF-36 "physical health" scale showed a 2.8-point increase in the TmG (P =.011) and a 1.5-point increase in the CG (P =.16). The change was smaller in the "mental health" scale, with a 0.5-point increase in the TMG (P =.64) and a 0.5-point decrease (P =.73) in the CG.

(B) Protocol acceptability: Adherence to protocol was measured by the percentage of WAP sessions held (89.2% ± 16.0). Almost all patients (98%) completed more than 50% of WAP sessions and more than 83% completed more than 75% of them. Only 0.5 messages per patient were missed, due to the mobile phone being turned off. Family support of the TmG patients was analyzed at 4 different levels: never (58% of patients), first week only (10%), 1 month (7%), and always (25%).

– Comments. A telemonitoring program, via mobile phone messages, appears to be useful for improving the risk profile in ACS survivors and can be an effective tool for secondary prevention, especially for overweight patients.

Other already carried out and finished projects are described briefly below

– Study variables. Outcome measures were resting BP, body mass index (BMI), smoking status, LDL-c, and glycated hemoglobin A1c (HbA1c), all measured at the initial and final visits for comparison. Their smoking status was determined by self-report and confirmed by a 1-step cotinine immunoassay in urine. The primary outcome was cardiovascular risk improvement (CRI), defined as the proportion of patients who achieve the goal of treatment in at least 1 CRF without exacerbation of any of the others. Treatment goals were as follows: (1) smoking cessation, (2) LDL-c less than 100 mg/dL, (3) BP lower than 140/90 mmHg, and (4) HbA1c less than 7%. Exacerbation of a CRF was defined as a 10% or more increase in BP, LDL-c, or HbA1c, with respect to initial levels. Secondary outcomes were: the proportion of patients achieving the treatment goal in each of the outcome measurements, quantitative changes in LDL-c, BP, BMI, and HbA1c (in diabetic patients), and changes in quality of life and level of anxiety. – Results. Four patients were lost in the followup (1.9%) and 5 died (2.5%), all in the CG. Seventeen patients left the study (8.4%), 12 in the TmG (11.8%) and 5 in the CG (4.9%) (RR = 2.38; 95% CI = 0.87-6.50; P =.08). Reasons for leaving the program in the TmG were stress associated with the use of the telemonitoring equipment in 3 patients, personal reasons in 7, and inability to handle the equipment in 2 patients; in the CG, all 5 attributed it to personal

Analysis on the basis of intention to treat showed that patients in the TmG were more likely (RR = 1.4; 95% CI = 1.1-1.7) to experience improvement in their CRF profile than patients in the CG (P =.010) at the end of 12 months. More TmG patients achieved the treatment goal in BP (62.1% vs 42.9%, P =.012; RR =1.4, 95% CI = 1.1-1.9) and in HbA1c among diabetic patients (86.4% vs 54.2%, P =.018; RR = 1.6; 95% CI = 1.1-2.4); there were no between-group differences for smoking cessation (80.7% vs 81.0%, P =.964; RR = 1.0; 95% CI = 0.9-1.1) or LDL-c (76.2% vs

Quantitative changes in continuous variables with comparison of the difference between the groups: Patients in the TmG showed significant changes in all variables with the exception of diastolic BP (DBP) (systolic BP [SBP], P =.0460; DBP, P =.237; LDL-c, P =.027; HbA1c, P =.001; BMI in overweight patients P =.003). In the CG, significant reductions were obtained in LDLc and DBP (SBP, P =.780; DBP, P =.001; LDL-c, P =.098; HbA1c, P =.239; BMI, P =.299). Body mass index diminished in the TmG and increased slightly in the CG. Triglyceride levels also decreased significantly in the TmG (P =.0001), but not in the CG (P =.435). No differences between-groups were found in physical activity (75% TmG vs 73% CG, P =.756) or medication adherence (99% in both groups, P =.980) both self-reported by patients. Nutritional habits were not explored. There were no significant differences between the scores obtained in SF-36 and State-Trait Anxiety Inventory tests at the initial visit in the 2 groups and changes were not significant between groups. At 12 months, the SF-36 "physical health" scale showed a 2.8-point increase in the TmG (P =.011) and a 1.5-point increase in the CG (P =.16). The change was smaller in the "mental health" scale, with a 0.5-point increase in the TMG (P =.64) and a 0.5-point

(B) Protocol acceptability: Adherence to protocol was measured by the percentage of WAP sessions held (89.2% ± 16.0). Almost all patients (98%) completed more than 50% of WAP sessions and more than 83% completed more than 75% of them. Only 0.5 messages per patient

reasons.

204 Telemedicine

76.6%, P =.948; RR = 1.0; 95% CI = 0.9-1.2).

decrease (P =.73) in the CG.

**•** Control and monitoring of self-care plans in asthma by means of a telemedicine platform. (FIS 02/1391. SEP 1201/02. AIRMED II Program). [57].

– Main objective. To evaluate the efficacy of a monitoring and self-care program for asthmatic patients based on telemedicine services. Secondary objectives: To evaluate the efficacy of the program as regards the adhesion to the self-care plans and to the adhesion to the monitoring of the FEM and FEV1. To evaluate the efficacy of the program as regards the clinical evolution of the asthma and quality of life of the patients with asthma.

– Type of study. Quasi-experimental project with two differentiated groups: study and control. 37 patients of the Pneumology Unit of the Hospital Universitario Puerta de Hierro, Madrid, Spain. October 2004 –May 2007. Intervention period, 12 months.

– Description intervention. All of the patients have their FEM and FEV1 monitored daily (morning and evening) (volume expired in the first second), by means of a portable spirometer, their symptoms and the medication taken. Those of the CG entered their data manually on adhoc designed forms and acted in accordance with the guidelines given during the consultation. The patients of the TmG followed the same medical protocol, although unlike the control group, they had the permanent support of the telemedicine platform which sent the protocol information by means of a mobile telephone (spirometry through CSD-GSM transmission, and symptoms and actions by means of a WAP session on GPRS-GSM). The patients of the TmG immediately and automatically received an SMS message as a reply which included informa‐ tion on their current state and the recommended medication guidelines in accordance with their personalized plan. The doctor also has permanent access to the information sent and evolution of each TmG patient so that he or she could individually supervise the development of the self-care plans.

– Results. There we no significant differences as regards the monitoring of the FEV1 at home and in the consultations of the study group. Compliance with the self-care plans was 70% in more than half of the patients. Adherence to the self-treatment plans was greater in the study group (95.28%) than in the control (93.09%).

– Comments. The tool that was designed to help in the decision-making process was highly evaluated by both the patients and professionals.

**•** AmIVital. Digital personal environment for health and wellbeing. (CENIT2007-1010). [58].

Within the (2008-2011) framework of a great technological project in which companies such as Siemens, Telefónica, Ericsson and Telvent have participated, together with 4 SMEs and 8 Universities and Public research Centers, our group has carried out the following studies:

– Type of study. A cross-sectional study was conducted in a health-area setting of the Madrid Autonomous Region, covering a population of 198,670 individuals aged over 14 years old. Multiple correspondences were analyzed to identify the clustering patterns of the conditions

PITES: Telemedicine and e-Health Innovation Platform

http://dx.doi.org/10.5772/57021

207

– Results. Forty-two percent (95% confidence interval [CI]: 41.8–42.2) of the registered population had at least one chronic condition. In all, 24.5% (95% CI: 24.3–24.6) of the population presented with multi-morbidity. In the correspondence analysis, 98.3% of the total information was accounted for by three dimensions. The following four, age- and sex-related co-morbidity patterns were identified: pattern B, showing a high co-morbidity rate; pattern C, showing a low co-morbidity rate; and two patterns, A and D, showing intermediate co-morbidity rates.

– Comments. Four co-morbidity patterns could be identified which grouped diseases as follows: one showing diseases with a high co-morbidity burden; one showing diseases with a low co-morbidity burden; and two showing diseases with an intermediate co-morbidity

Current projects as envisaged projects of our group are described briefly below.

**•** Monitoring of the elderly in assisted spaces for independent living. [FIS PI08-0435]

better overall geriatric evaluation and better attention to the elderly in their homes.

of the telephone, for a week-10 days to obtain basic values for the behavior pattern.

– Monitoring of an advanced Spanish EPOC cohort (CEPA). [FIS PS09-01787].

Ramón y Cajal, Madrid, Spain. Commencement: February 2010.

– Comments. Finalization 1st phase envisaged December 2012.

– Main objective. : To study how the monitoring of domestic activities may help to achieve a

– Type of study. Pilot study with 30 patients at a geriatric unit at the Hospital Universitario

– Intervention description. Two information methods were used: one subjective, by means of an integrated evaluation scale: Barthel, Lawton-Brody, Mini-Nutritional, Mini-Mental State Exam, Geriatric Depression Scale, Morisky-Green and Short Physical Performance Battery). Another objective: by means of an environmental monitoring. The following was installed in the homes of each patient: 5 presence detectors, 2 magnetic door opening sensors (refrigerator and front door), 2 pressure sensors (bed and armchair), 1 sensor in their pill box, 1 for the use

– Study variables. 15 items were analyzed related to: Therapeutic Control, In-house Mobility, Outdoor Mobility, Personal Hygiene, Cleanliness: Urination/Bowel movements, Dressing, Domestic activities, Emotional, Memory, Orientation, Meals, Personal, Telephone use.

– Main objective. Describe the clinical course of the EPOC in terms of clinical data, functional and radiological. Secondary objectives: Describe the incident mortality and causes of death.

targeted.

burden.

**4.2. Current projects**

*4.2.1. Our own projects*

– Study of the prevalence and co-morbidity of heart failure in the family practice. [59].

– Type of study. A cross-sectional, observational descriptive study set in a health area of the Community of Madrid, Spain. The study was carried out in a population of 198 670 individuals over 14 years of age, attended to by 129 specialists in family medicine. The patient was considered to have HF when this diagnosis (ICPC code K77) appeared in his or her electronic medical record. The prevalence of HF was quantified and its association with another 25 chronic diseases was analyzed.

– Results. The prevalence of HF was 6.9%, 7.9% among women and 5.9% among men. Patients with HF had a high rate of chronic co-morbidity, with an average of 5.2 + 2.1 chronic diseases. Only 3% of the patients present with isolated HF and >60% have four or more additional chronic problems. Hypertension, cardiac arrhythmias, hyperlipidaemia, obesity and diabetes mellitus are the chronic diseases most frequently detected in HF patients.

– Comments. Patients with HF frequently visit the offices of family physicians, presenting with a high rate of cardiac and non-cardiac co-morbidity that proves to be a challenge on the clinical level and in terms of the organization of health care services.

– Study of disability measured by WHO-DAS II. [60].

– Type of study. Samples of consecutive patients diagnosed with COPD (102), CHF (99), and stroke (99) were taken from 1,053 primary care users in the southern area of the autonomous region of Madrid. The patients were informed of the study and were assessed in their homes by trained field workers using the World Health Organization Disability Assessment Schedule II (WHO-DAS II).

– Results. None of the groups had extreme disability on their overall WHO-DAS II scores. The prevalence of severe disability differed among the groups and was highest for stroke and CHF (33.33% and 29.29%, respectively) and lowest for COPD (14.71%). The three groups shared two similar traits, namely, a higher prevalence of disability among women than men, and a specific pattern by domain, with the highest prevalence of severe/extreme limitations being found in household life activities and mobility. Severe restrictions in Social Participation were more frequent in patients with stroke and CHF. The group with moderate disability according to the overall WHODAS II score (n=94) showed a high prevalence of severe limitations in mobility, life activities and self-care.

– Comments. Disability among non-institutionalized persons with COPD, CHF and stroke is frequent and shows gender- and domain-related patterns similar to those described in a population-based study performed using the WHO-DAS II in elderly persons in Spain. ICFvalidated disability categories could be useful in epidemiological surveys, individual assess‐ ments and primary care data monitoring systems.

– Co-morbidity Patterns in Patients with Chronic Diseases in General Practice. [61].

– Type of study. A cross-sectional study was conducted in a health-area setting of the Madrid Autonomous Region, covering a population of 198,670 individuals aged over 14 years old. Multiple correspondences were analyzed to identify the clustering patterns of the conditions targeted.

– Results. Forty-two percent (95% confidence interval [CI]: 41.8–42.2) of the registered population had at least one chronic condition. In all, 24.5% (95% CI: 24.3–24.6) of the population presented with multi-morbidity. In the correspondence analysis, 98.3% of the total information was accounted for by three dimensions. The following four, age- and sex-related co-morbidity patterns were identified: pattern B, showing a high co-morbidity rate; pattern C, showing a low co-morbidity rate; and two patterns, A and D, showing intermediate co-morbidity rates.

– Comments. Four co-morbidity patterns could be identified which grouped diseases as follows: one showing diseases with a high co-morbidity burden; one showing diseases with a low co-morbidity burden; and two showing diseases with an intermediate co-morbidity burden.

#### **4.2. Current projects**

Within the (2008-2011) framework of a great technological project in which companies such as Siemens, Telefónica, Ericsson and Telvent have participated, together with 4 SMEs and 8 Universities and Public research Centers, our group has carried out the following studies:

– Type of study. A cross-sectional, observational descriptive study set in a health area of the Community of Madrid, Spain. The study was carried out in a population of 198 670 individuals over 14 years of age, attended to by 129 specialists in family medicine. The patient was considered to have HF when this diagnosis (ICPC code K77) appeared in his or her electronic medical record. The prevalence of HF was quantified and its association with another 25

– Results. The prevalence of HF was 6.9%, 7.9% among women and 5.9% among men. Patients with HF had a high rate of chronic co-morbidity, with an average of 5.2 + 2.1 chronic diseases. Only 3% of the patients present with isolated HF and >60% have four or more additional chronic problems. Hypertension, cardiac arrhythmias, hyperlipidaemia, obesity and diabetes

– Comments. Patients with HF frequently visit the offices of family physicians, presenting with a high rate of cardiac and non-cardiac co-morbidity that proves to be a challenge on the clinical

– Type of study. Samples of consecutive patients diagnosed with COPD (102), CHF (99), and stroke (99) were taken from 1,053 primary care users in the southern area of the autonomous region of Madrid. The patients were informed of the study and were assessed in their homes by trained field workers using the World Health Organization Disability Assessment Schedule

– Results. None of the groups had extreme disability on their overall WHO-DAS II scores. The prevalence of severe disability differed among the groups and was highest for stroke and CHF (33.33% and 29.29%, respectively) and lowest for COPD (14.71%). The three groups shared two similar traits, namely, a higher prevalence of disability among women than men, and a specific pattern by domain, with the highest prevalence of severe/extreme limitations being found in household life activities and mobility. Severe restrictions in Social Participation were more frequent in patients with stroke and CHF. The group with moderate disability according to the overall WHODAS II score (n=94) showed a high prevalence of severe limitations in

– Comments. Disability among non-institutionalized persons with COPD, CHF and stroke is frequent and shows gender- and domain-related patterns similar to those described in a population-based study performed using the WHO-DAS II in elderly persons in Spain. ICFvalidated disability categories could be useful in epidemiological surveys, individual assess‐

– Co-morbidity Patterns in Patients with Chronic Diseases in General Practice. [61].

mellitus are the chronic diseases most frequently detected in HF patients.

level and in terms of the organization of health care services.

– Study of disability measured by WHO-DAS II. [60].

– Study of the prevalence and co-morbidity of heart failure in the family practice. [59].

chronic diseases was analyzed.

206 Telemedicine

II (WHO-DAS II).

mobility, life activities and self-care.

ments and primary care data monitoring systems.

#### *4.2.1. Our own projects*

Current projects as envisaged projects of our group are described briefly below.

**•** Monitoring of the elderly in assisted spaces for independent living. [FIS PI08-0435]

– Main objective. : To study how the monitoring of domestic activities may help to achieve a better overall geriatric evaluation and better attention to the elderly in their homes.

– Type of study. Pilot study with 30 patients at a geriatric unit at the Hospital Universitario Ramón y Cajal, Madrid, Spain. Commencement: February 2010.

– Intervention description. Two information methods were used: one subjective, by means of an integrated evaluation scale: Barthel, Lawton-Brody, Mini-Nutritional, Mini-Mental State Exam, Geriatric Depression Scale, Morisky-Green and Short Physical Performance Battery). Another objective: by means of an environmental monitoring. The following was installed in the homes of each patient: 5 presence detectors, 2 magnetic door opening sensors (refrigerator and front door), 2 pressure sensors (bed and armchair), 1 sensor in their pill box, 1 for the use of the telephone, for a week-10 days to obtain basic values for the behavior pattern.

– Study variables. 15 items were analyzed related to: Therapeutic Control, In-house Mobility, Outdoor Mobility, Personal Hygiene, Cleanliness: Urination/Bowel movements, Dressing, Domestic activities, Emotional, Memory, Orientation, Meals, Personal, Telephone use.

– Comments. Finalization 1st phase envisaged December 2012.

– Monitoring of an advanced Spanish EPOC cohort (CEPA). [FIS PS09-01787].

– Main objective. Describe the clinical course of the EPOC in terms of clinical data, functional and radiological. Secondary objectives: Describe the incident mortality and causes of death. Describe the phenotypic features and group them together in their respective dimensions or factors. Describe the assorted and incident morbidity. Describe the health care load on the health system (use of medication and frequency of doctor and hospitals consultations). Explore the viability of the application of the weekly questionnaires.

– Main objective. Updating of the PITES platform through the creation of an environment for the development of technological support of new devices for biomedical, contextual and environmental monitoring, and new applications and services based on Internet and Internet devices. The inclusion of new archetypes and knowledge management server and a new medical report and information management server. Development of: a) new client applica‐ tions for access to both servers, b) safety policy in accordance with ISO EN 13606, and c)

PITES: Telemedicine and e-Health Innovation Platform

http://dx.doi.org/10.5772/57021

209

In 2009 the possibility opened up for the PITES platform to be used by other research groups within the Spanish National Health Service. Without describing them for reasons of confiden‐

**•** Monitoring and control based on telemedicine patients with (TAO-E) oral anticoagulation treatment. [FIS PI09-90094]. Bioengineering and Telemedicine Unit. Hospital Universitario

**•** Methods and tools for the design and implementation of telemedicine and e-health services for the attention of chronic patients. [FIS PI09-90518]. Hospital Universitario Virgen del

**•** Integral attention to aged chronic-dependent people. Evaluation of the interlinked provision of health and social services - (AYUDA). [FIS PI09-90549]. Barbastro Health Sector. Huesca.

**•** Hospitalization at home and rare illnesses in Navarra. Evaluation of the home health care and identification of added-value e-health services. [FIS PI09-90317]. Medical-Technological

**•** Innovative health care services integrated for chronic patients. [FIS PI09-90634]. Hospital

**•** Effectiveness of a telemedicine program in the monitoring and control de patients con metabolic syndrome within the ambit of primary attention. [FIS PI09/90285]. Management

**•** T-CUIDAENCASA: Innovation platform at home telemedicine services. [FIS PI12/00673].

**•** Regional scalability of the integrated attention services and aid in the clinical decision. [FIS

applications for advanced visualization.

Puerta de Hierro. Majadahonda. Madrid.

Complex of Navarra. Pamplona. Navarra.

Barbastro Health Sector. Huesca. Aragón

of Primary Attention. Albacete. Castilla la Mancha.

**•** Approved projects, envisaged to begin throughout 2013.

PI12-01241]. Hospital Clínic de Barcelona. Cataluña.

*4.2.2. Projects of other groups*

Rocío. Sevilla. Andalucía.

Clinic. Barcelona. Cataluña.

Aragón.

– Comments. Commencement envisaged January 2013.

tiality, current projects and envisaged projects are cited below.

**•** Current projects, which are envisaged to finish throughout 2013.

– Type of study. Observational study, longitudinal and concurrent of two groups of patients with advanced EPOC. 214 patients were enrolled by 32 pneumologists and followed by 32 nurses from 32 hospitals from all of the regions, Spain. Commenced November 2011. Inter‐ vention period: 18 months.

– Intervention description. In both groups: Programmed weekly visits to pneumonological services of the corresponding hospital. The TmG patients will answer a weekly questionnaire from home of 12 questions related to their state of health. They can choose the internet, mobile telephone or interactive voice by means of a fixed or mobile telephone (IVR) to fill in and send their weekly questionnaire.

– Study variables. In the weekly visits of both groups: personal and demographic data, health model, diagnostics, risk factors, symptoms, signs, current treatment, use of resources, quality of life (CAT), anxiety/depression (HAD), as well as tests to determine biochemical and blood count, pulmonary function, blood-gas analysis, BODE, blood, TAC, echocardiogram. In the weekly questionnaire: a) degree of breathlessness, b) fever, c) expectoration, d) nocturnal symptoms, e) treatment, f) level of activity, g) tobacco, and h) use of health resources.

– Comments. Finalization envisaged in October 2013.

**•** REHABILITA. Disruptive technologies for future rehabilitation. [CENIT2009-1043]. [62]

Support the interoperability in the development of the project by means of the use of medical report services and archetypes of the PITES platform. The medical report services and archetypes are used as a support for the sending and consulting of information from the monitoring devices of the patients during the development of the REHABILITA services platform.

Semantically interoperable interconnection of the servers of the REHABILITA platform with the information systems of the health centers involved. The PITES platform is being used as an information and archetypes buffer for the reading of the information of the systems of the health organizations (acquisition of data for the preparation of therapeutic explanations) and for the storage of the results of the rehabilitation sessions in the electronic clinical records storage systems.

Development in the PITES platform of an observatory of disruptive technologies in rehabili‐ tation as a collaboration Web space of the researchers of the project; by means of its analysis and study; then applying it in the aspects of use for innovation activities in the said domain.

– Comments. Finalization envisaged April 2013.

**•** PITES-ISA. Innovation platform in new telemedicine and e-health services: Definition, design and development of tools for interoperability, patient safety and help in decision making. [FIS PI12-00508.]

– Main objective. Updating of the PITES platform through the creation of an environment for the development of technological support of new devices for biomedical, contextual and environmental monitoring, and new applications and services based on Internet and Internet devices. The inclusion of new archetypes and knowledge management server and a new medical report and information management server. Development of: a) new client applica‐ tions for access to both servers, b) safety policy in accordance with ISO EN 13606, and c) applications for advanced visualization.

– Comments. Commencement envisaged January 2013.

#### *4.2.2. Projects of other groups*

Describe the phenotypic features and group them together in their respective dimensions or factors. Describe the assorted and incident morbidity. Describe the health care load on the health system (use of medication and frequency of doctor and hospitals consultations). Explore

– Type of study. Observational study, longitudinal and concurrent of two groups of patients with advanced EPOC. 214 patients were enrolled by 32 pneumologists and followed by 32 nurses from 32 hospitals from all of the regions, Spain. Commenced November 2011. Inter‐

– Intervention description. In both groups: Programmed weekly visits to pneumonological services of the corresponding hospital. The TmG patients will answer a weekly questionnaire from home of 12 questions related to their state of health. They can choose the internet, mobile telephone or interactive voice by means of a fixed or mobile telephone (IVR) to fill in and send

– Study variables. In the weekly visits of both groups: personal and demographic data, health model, diagnostics, risk factors, symptoms, signs, current treatment, use of resources, quality of life (CAT), anxiety/depression (HAD), as well as tests to determine biochemical and blood count, pulmonary function, blood-gas analysis, BODE, blood, TAC, echocardiogram. In the weekly questionnaire: a) degree of breathlessness, b) fever, c) expectoration, d) nocturnal

symptoms, e) treatment, f) level of activity, g) tobacco, and h) use of health resources.

**•** REHABILITA. Disruptive technologies for future rehabilitation. [CENIT2009-1043]. [62]

Support the interoperability in the development of the project by means of the use of medical report services and archetypes of the PITES platform. The medical report services and archetypes are used as a support for the sending and consulting of information from the monitoring devices of the patients during the development of the REHABILITA services

Semantically interoperable interconnection of the servers of the REHABILITA platform with the information systems of the health centers involved. The PITES platform is being used as an information and archetypes buffer for the reading of the information of the systems of the health organizations (acquisition of data for the preparation of therapeutic explanations) and for the storage of the results of the rehabilitation sessions in the electronic clinical records

Development in the PITES platform of an observatory of disruptive technologies in rehabili‐ tation as a collaboration Web space of the researchers of the project; by means of its analysis and study; then applying it in the aspects of use for innovation activities in the said domain.

**•** PITES-ISA. Innovation platform in new telemedicine and e-health services: Definition, design and development of tools for interoperability, patient safety and help in decision

the viability of the application of the weekly questionnaires.

– Comments. Finalization envisaged in October 2013.

– Comments. Finalization envisaged April 2013.

making. [FIS PI12-00508.]

vention period: 18 months.

208 Telemedicine

their weekly questionnaire.

platform.

storage systems.

In 2009 the possibility opened up for the PITES platform to be used by other research groups within the Spanish National Health Service. Without describing them for reasons of confiden‐ tiality, current projects and envisaged projects are cited below.


**•** Implementation of tools to aid in the decision, interoperability and safety for an e-service for the early detection of exacerbations in EPOC patients "frequent-user phenotype ". [FIS PI12/01305]. Hospital Universitario Puerta de Hierro. Majadahonda. Madrid.

[3] Haverhals LM, Lee CA, Siek KA, Darr CA, Linnebur SA, Ruscin JM, Ross SE Older Adults with Multi-Morbidity: Medication Management Processes and Design Impli‐

PITES: Telemedicine and e-Health Innovation Platform

http://dx.doi.org/10.5772/57021

211

[4] Communication from the Commission to the European Parliament and the Council. Taking forward the Strategic Implementation Plan of the European Innovation Part‐

[5] World Health Organization WHO: Essential Health Technologies. (2003). Strategy 2004-2007: e-Health for Health-care Delivery. http://www.who.int/entity/eht/en/

[6] Report of the WHO Global Observatory for e-Health Building Foundations for e-

[7] European Union EU: Initiative e-Europe 2005. http://eur-lex.europa.eu/LexUriServ/ LexUriServ.do?uri= COM:2002:0263:FIN:ES:PDF (accessed 6 December 2007).

[8] European Union EU: Initiative i2010. http://ec.europa.eu/information\_society/

[9] Innovation Report UK Department of Trade and Industry. Competing the Global

[10] Pagliari C. Design and Evaluation in e-Health: Challenges and Implications for an In‐

[11] Weingart P. Interdisciplinarity: the paradoxical discourse. Practising interdisciplinar‐

[12] Glouberman S, Zimmerman B.J. Complicated and complex systems: What would successful reform of Medicare look like? Discussion paper #8 Commission on the Fu‐

[13] Plsek PE, Greenhalgh T. The challenge of complexity in health care. British Medical

[14] Millar WL, McDaniel RR, Crabtree B.F. Practice Jazz: Understanding Variation in Family Practices Using Complexity Science. Journal of Family Practice 2001;50(10).

[15] Sweeney K, Griffiths F. Complexity and Healthcare: An Introduction. London: Radcl‐

[16] Litaker D, Tomolo A, Liberatore V, Stange KC, Aron D. Using complexity theory to build interventions that improve health care delivery in primary care. J Gen Intern

[17] Medical Research Council. A framework for development and evaluation of RTCs

cations for Personal Health Applications J Med Internet Res 2011;13(2):e44

nership on Active and Healthy Ageing. COM/2012/083 final. 2012.

eHealth\_HCD.pdf (accessed 5 December 2007).

eeurope/i2010/index\_ en.htm (accessed 6 December 2007).

terdisciplinary Field. J Med Internet Res 2007;9(2): e15.

for complex interventions to improve health. 2000.

ity. Toronto, ON: University of Toronto Press; 2000. p25-42.

Economy: The Innovation Challenge. London, UK: HMSO. 2003.

Health: Progress of Member States. 2006.

ture of Health Care in Canada. 2002.

Journal 2001 323:625-8.

Med 2006;21 30-34.

iff, 2002.

