1. Cellular Phone-Based Technologies for Monitoring Of Patients With Diabetes: a Systematic Review and Meta Analysis Systematic Review And Meta-Analysis Class 3 PhD João Fonseca Introdução à Medicina II

2. Overview Introduction Motivation Research question Aims Methods and Participants Systematic review and Meta-analysis Query Inclusion and Exclusion criteria Sampling methods Data collection Studies’ quality Statistical analysis and Results Diabetes and the chronic diseases Characteristics of the studies Secondary variables Outcomes Meta-analysis Discussion Main findings Limitations Critical comparison with other studies Conclusions

3. Introduction Motivation Research question Aims Methods and Participants Systematic review and Meta-analysis Query Inclusion and Exclusion criteria Sampling methods Data collection Studies’ quality Statistical analysis and Results Diabetes and the chronic diseases Characteristics of the studies Secondary variables Outcomes Meta-analysis Discussion Main findings Limitations Critical comparison with other studies Conclusions

4. Chronic diseases 60% of all deaths [1] Slow progression Mobile phone based tecnhologies Applied in management of diseases [3] Increasing international interest [2] [1]http://www.who.int/en/, available at 1-11-2007 [2] Pinnock Hilary, Slack Roger, Pagliari Claudia, Price David, Sheikh Aziz. Understanding the potential role of mobile phone-based monitoring on asthma self- management: qualitative study. Clinical and Experimental Allergy. May 2007. 37(5):794-802; Available at: www.pubmed.com 26-10-2007. [3] Ryan D, Cobern W, Wheeler J, Price D, Tarassenko L; Mobile Phone Technology in the Management of Asthma; Journal of Telemedicine and Telecare 2005; 11 Suppl 1:4Kollmann et al., 2007 [6]-6; Available at: www.pubmed.com 26-10-2007 Motivation

5. Patient with diabetes Quick communication of symptoms [4] Healthcare professional Communication of adapted treatment Fig. 1_ The role of CPT in the monitoring of patients with chronic diseases [4] Morak J, Kollmann A, Schreier G; Feasibility and usability of a home monitoring concept based on mobile phones and near field communication (NFC) technology; Medinfo. 2007; 12 (Pt 1):112-6; Available at: www.pubmed.com 26-10-2007.

6. Diabetes High mortality High morbidity Increasing prevalence in society [5] Selection of one disease Clear and structured article Focused article [5] Amosa F.; Mccarty D. J.; Zimmet P., The rising global burden of diabetes and its implications: estimates and projections to the year 2010 ;Diabetic medicine ; 1997, vol.14, pp S7-S84, SUP5

7. “Does cellular phone based tecnhologies monitoring improve diabetes patients’ clinical outcomes?” Research question

8. Aims * To describe the proportion of published studies about CPT regarding major chronic diseases. * To investigate if CPT improves patients’ medical state Glycosylated haemoglobin Fasting plasma glycemia

9. Introduction Motivation Research question Aims Methods and Participants Systematic review and Meta-analysis Query Inclusion and Exclusion criteria Sampling methods Data collection Studies’ quality Statistical analysis and Results Diabetes and the chronic diseases Characteristics of the studies Secondary variables Outcomes Meta-analysis Discussion Main findings Limitations Critical comparison with other studies Conclusions

10. Search CollectSummarize Evidence collected from articles Systematic review and Meta-analysis

11. ((monitoring) OR (telemonitoring)) AND ((cellular phone-based technologies) OR (mobile phone-based technologies) OR (cellular phone) OR (mobile phone)) AND ((chronic diseases) OR (chronic patients) OR (cancer) OR (nephrologic diseases) OR (kidney insufficiency) OR (asthma) OR (respiratory chronic diseases) OR (COPD) OR (diabetes) OR (cardiovascular disease)). Query

12. Inclusion criteriaExclusion criteria * Articles published in the last 10 years * Articles containing original data * Cellular phone-based technologies (CPT)‏ * Articles about the application of CPT in patients * Articles regarding diabetes * Articles regarding comparison studies * Articles regarding the evolution of the clinical state of the patient * Articles in English, Spanish and French * Use of cellular-phone for interviewing patients about other issues unrelated to disease monitoring * Articles that describe technologies and their development Inclusion and Exclusion criteria

13. 3314 3 Sampling methods Fig.2 – Distribution of articles repeated among databases

14. Read abstract of 160 (inclusion and exclusion criteria) 50 repeated among databases Requested by e-mail 6 with no full-text 3 repeated within databases Read full-text of 21 (inclusion and exclusion criteria) 80 excluded 7 excluded 9 with no abstract Systematic review 5 articles included 4 excluded (no control group or no postest values) 2 articles included Meta-analysis 2 answered1 included

15. * year of publication * country of origin * type of study * n intervention * n controls * age group * Glycosylated haemoglobin Control/intervention * Fasting plasma glycemia Control/intervention Children : 0-14 Youth: 15-17 Adults: 18-65 Elderly: +65 Data collection

16. Table 1 - Quality Criteria used to evaluate the final articles included, adapted from “Extending the CONSORT Statement to Randomized Trials of Nonpharmacologic Treatment: Explanation and Elaboration ” Studies’ quality Study sectionQuality criteria Introduction1. Objectives and/or hypotheses of the study Methods Intervention 2. Precise details of the interventions intended for each group and how they were actually administered Outcomes3. Clearly defined primary and secondary outcome measures Statistical methods4. Statistical methods used to compare groups for primary outcome(s) Recruitment5. Duration of recruitment and follow-up Baseline data6. Not existence of different characteristics in each group Numbers analyzed7. Number of participants in each group included in each analysis Outcomes and estimation 8. For each primary and secondary outcome, a summary of results for each group and the estimated effect size and its precision (e.g., 95% confidence interval) Discussion Generalizability 9. Generalizability (external validity) of the trial findings according to the intervention, comparators, patients, and care providers and centers involved in the trial Overall evidence10. General interpretation of the results in the context of current evidence

17. Table 2 – Articles classification according to quality criteria Criteria Studies Total Kollmann et al., 2007 [6] Kim et al.,2006 [7] Kim et al., 2007 [8] Benhamou et al., 2007 [9] Vahatalo et al., 2004 [10] Ladyzynski et al. 2001 [11] 11111116 21111116 31011115 41111116 51111116 61111015 71111116 81111015 90100001 101111116 Total999979

18. Introduction Motivation Research question Aims Methods and Participants Systematic review and Meta-analysis Query Inclusion and Exclusion criteria Sampling methods Data collection Studies’ quality Statistical analysis and Results Diabetes and the chronic diseases Characteristics of the studies Secondary variables Outcomes Meta-analysis Discussion Main findings Limitations Critical comparison with other studies Conclusions

19. Graphic 1 - Distribuition of chronic diseases among obtained articles. Total number of articles obtained regarding chronic diseases N= 81 Diabetes and chronic diseases

20. Table 3 - Included articles characteristics Characteristics of the studies Article Year of publication CountryType of studyn interventionn controlAge group Ladyzynski et al., 2001 [11] 2001PolandQuasi-experimental15Adults Vahatalo et al., 2004 [10] 2004FinlandQuasi-experimental102101Adults Kim et al., 2006 [7] 2006 South Korea Quasi-experimental33Adults Kollmann et al., 2007 [6] 2007AustriaClinical trial10Adults Kim et al., 2007 [8] 2007 South Korea Clinical trial2526Adults Benhamou et al., 2007 [9] 2007France Randomized crossover study 30 (29 glycemia) 30 (28 glycemia) Adults

21. Table 4 - Secondary variables Secondary variables Secondary Variables Articles Kollmann et al., 2007 [6] Kim et al., 2006 [7] Kim et al., 2007 [8] Benhamou et al., 2007 [9] Vahatalo et al., 2004 [10] Ladyzynski et al., 2001 [11] Glycemia above 150 mg/dlp>0,05 Glycemia in normal range (80-150 mg/dl) p>0,05 Glycemia below 50 mg/dlp>0,05 Two hours post-meal glucose (mg/dl) p<0,05 Mean blood glucose (mg/dl)P< 0.05 Physical Exercise (d/wk) p<0,05 Diabetic medication taking (d/wk) p<0,05 Foot Care (d/wk) p<0,05 Diabetic diet (d/wk) p>0,05 DQoL p<0,05 Satisfaction with life p<0,05

22. Table 5 - Extracted variables Outcomes Articles Glycosylated haemoglobin % intervention Glycosylated haemoglobin % control Fasting plasma glycemia (mg/dl) intervention Fasting plasma glycemia (mg/dl) control PosttestPretestPosttestPretestPosttestPretestPosttestPretest Vahatalo et al., 2004 [10] 7.7±1.3 7.9± 1.5 0.45±1.20.35 ± 1.0 Kollmann et al., 2007 [6] 7,5± 0,97,9± 1,1 141,2± 23,1 141,8± 22,5 Kim et al., 2007 [8] 7,04± 1,39 8,09± 1,72 7,70± 0,90 7,59± 1,09 145,7± 39,7 151,1± 25,7 149,5± 39,3 142,2± 24,1 Kim et al., 2006 [7] 7,0± 1,18,1± 2,1 -1,1± 2,1 Benhamou et al., 2007 [9] 8.18 ± 0.59 8.31 ± 0.65 8.34 ± 0.67 8.22 ± 0.72 160 ± 20166 ± 23167 ± 21162 ± 22 – 0.14 ± 0.530.12 ± 0.65– 5 ± 174 ± 18 Ladyzynski et al., 2001 [11] 7,1 ± 1,18,0 ± 1,1

23. Fig. 3 - Glycosilated haemoglobin forest plot Meta-analysis Glycosilated haemoglobin

24. Fig.4 - Fasting plasma glycemia forest plot Fasting plasma glycemia

25. Introduction Motivation Research question Aims Methods and Participants Systematic review and Meta-analysis Query Inclusion and Exclusion criteria Sampling methods Data collection Studies’ quality Statistical analysis and Results Diabetes and the chronic diseases Characteristics of the studies Secondary variables Outcomes Meta-analysis Discussion Main findings Limitations Critical comparison with other studies Conclusions

26. Ladyzynski et al., 2001 [11] Vahatalo et al., 2004 [10] Kim et al., 2006 [7] Kollmann et al., 2007 [6] Benhamou et al., 2007 [9] Kim et al., 2007 [8] Clinical State SNS S Adherence S S (Diet NS) QoL and Satisfaction with life S Glycosilated haemoglobin (Posttest-Pretest int.) S NS (increase) SSNSS Glycosilated haemoglobin (Posttest int. vs control) NS (decrease) Fasting plasma glycemia (Posttest- Pretest int.) NS Fasting plasma glycemia (Posttest int. vs control) NS (decrease) Quality 979999 Main findings Table 6 – Summary of obtained results

27. Ladyzynski et al., 2001 [11] Vahatalo et al., 2004 [10] Kim et al., 2006 [7] Kollmann et al., 2007 [6] Benhamou et al., 2007 [9] Kim et al., 2007 [8] Clinical State SNS S Adherence S S (Diet NS) QoL and Satisfaction with life S Quality 979999 Clinical State: Measured in different ways Impossible to compare Adherence: Significant except for Diabetic diet Adherence seem to increase with the use of CPT QoL and Satisfaction with life: Significant This variable seem to increase with the use of CPT Table 7 – Summary of results obtained for secondary variables and studies quality classification

28. Ladyzynski et al., 2001 [11] Vahatalo et al., 2004 [10] Kim et al., 2006 [7] Kollmann et al., 2007 [6] Benhamou et al., 2007 [9] Kim et al., 2007 [8] Glycosilated haemoglobin (Posttest-Pretest int.) S NS (increase) SSNSS Glycosilated haemoglobin (Posttest int. vs control) NS (decrease) Quality 979999 Glycosilated haemoglobin: Increases in Vahatalo et al., 2004 [10] (Quality 7) Decreases significantly in 4 of the studies Meta-analysis not significant, although decreases Measured in different ways Included studies are different Table 8 – Summary of results obtained for glycosilated haemoglobin

29. Ladyzynski et al., 2001 [11] Vahatalo et al., 2004 [10] Kim et al., 2006 [7] Kollmann et al., 2007 [6] Benhamou et al., 2007 [9] Kim et al., 2007 [8] Fasting plasma glycemia (Posttest- Pretest int.) NS Fasting plasma glycemia (Posttest int. vs control) NS (decrease) Quality 979999 Fasting plasma glycemia: Measured in 3 studies Decreases not significantly in every studies Meta-analysis not significant, although decreases Table 9 – Summary of results obtained for fasting plasma glycemia

30. Fasting plasma glycemia: Measured in 3 studies Decreases not significantly in every studies Meta-analysis not significant, although decreases Clinical State: Measured in different ways Impossible to compare Adherence: Significant except for Diabetic diet Adherence seem to increase with the use of CPT QoL and Satisfaction with life: Significant This variable seem to increase with the use of CPT Glycosilated haemoglobin: Decreases significantly in 4 of the studies Meta-analysis not significant, although decreases

31. Limitations and Critical comparison with other studies Small number of studies Sensitivity of the query? Too restrictive exclusion criteria? Requested articles? Data bases explored? Small number of published articles (recent area of interest)? Published articles have low quality? Quality of the studies Studies of short duration No control group Ways of measuring Low number of participants Paré et al., 2007 [12] (Systematic review) Bigger number of studies Criteria applied less restrictive (older articles) Different databases explored Conclusions Glycosilated haemoglobin and Fasting plasma glycemia decrease No meta-analysis found

32. 31% of all articles report to diabetes No meta-analysis found Increasing number of patients with chronic diseases Increasing mortality Increasing costs for the National Health System There is no cure, only regular treatments Systematic review pointing the same conclusions Increase of the adherence, clinical state and quality of life even if slightly Older population Changes in the way of life Inconclusive results because of the small number of studies Other chronic diseases are even less studied Necessity of more studies and with more quality Conclusions

33. Susana Carrilho Sara CoelhoFernando Sá Diogo Miguel Alexandra AzevedoAna Pessoa Ana Lisboa Ana Luísa GraçaPedro Lopes Ana Luísa Padilhó Joana Carvalho Maycoll Vieira Pedro Souteiro Class 3

34. [1]http://www.who.int/en/, available on 1-11-2007 [2] Hilary Pinnock, Roger Slack, Claudia Pagliari, David Price, Aziz Sheikh; Understanding the potential role of mobile phone-based monitoring on asthma self-management: qualitative study; Clinical and Experimental Allergy. 2007 May; 20077(5):794-802; Available at: www.pubmed.com 26-10-2007. [3] Ryan D, Cobern W, Wheeler J, Price D, Tarassenko L; Mobile Phone Technology in the Management of Asthma; Journal of Telemedicine and Telecare 2005; 11 Suppl 1:4Kollmann et al., 2007 [6]-6; Available at: www.pubmed.com 26-10-2007 [4] Morak J, Kollmann A, Schreier G; Feasibility and usability of a home monitoring concept based on mobile phones and near field communication (NFC) technology; Medinfo. 2007; 12 (Pt 1):112-6; Available at: www.pubmed.com 26-10- 2007. [5] Amosa F.; Mccarty D. J.; Zimmet P., The rising global burden of diabetes and its implications: estimates and projections to the year 2010 ;Diabetic medicine ; 1997, vol.14, pp S7-S84, SUP5 [6] Kollmann A, Riedl M, Kastner P, Schreier G, Ludvik B. Feasibility of a mobile phone-based data service for functional insulin treatment of type 1 diabetes mellitus patients. J Med Internet Res. Dez 2007; 31;9(5):e36. [7] Kim HS. Impact of Web-based nurse's education on glycosylated haemoglobin in type 2 diabetic patients; J Clin Nurs; Jul 2007; 16(7):1361-6. [8] Kim HS; A randomized controlled trial of a nurse short-message service by cellular phone for people with diabetes; Int J Nurs Stud; Jul 2007; 687-92. [9] Benhamou, P, Melki, V, Boizel R, et al. One-year efficacy and safety of Web-based follow-up using cellular phone in type 1 diabetic patients under insulin pump therapy: the PumpNet study. Diabetes & Metabolism. Jun 2007; 33(2): 220- 226. [10] Vahatalo, M.A., Virtamo, H.E., Viikari, J.S., Ronnemaa, T.; Cellular phone transferred self blood glucose monitoring: Prerequisites for positive outcome; Practical Diabetes International; 2004; 21 (5); 192-194. [11] Ladyzynski P, Wojcicki J, Krzymien J, et al. Teletransmission system upporting intensive insulin treatment of out-clinic type 1 diabetic pregnant women: Technical assessment during 3 years’ application. The International Journal of Artificial Organs. 2001. 24(3). [12] Paré G., Jaana M., Sicotte C.; Systematic Review of Home Telemonitoring for Chronic Diseases: The Evidence Base; J Am Med Inform Assoc. May–Jun 2007; 14(3): 269–277. References