Do automated text messages increase adherence to acne therapy? Results of a randomized, controlled trial

Do automated text messages increase adherence to acne therapy? Results of a randomized, controlled trial

Do automated text messages increase adherence to acne therapy? Results of a randomized, controlled trial Andreas Boker, MD,a H. Jill Feetham, BS,a Apr...

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Do automated text messages increase adherence to acne therapy? Results of a randomized, controlled trial Andreas Boker, MD,a H. Jill Feetham, BS,a April Armstrong, MD,b Patricia Purcell, MD,a and Heidi Jacobe, MD, MSCSa Dallas, Texas, and Davis, California Background: Acne is a common skin condition often requiring complex therapeutic regimens. Patient nonadherence to prescribed medication regimens is a factor in treatment failure. Objective: The goal of this study was to determine if daily automated text messages would result in increased adherence to recommended use of topical acne medication and consequently greater improvement in acne. Methods: Forty patients with mild to moderate acne were prescribed clindamycin/benzoyl peroxide 1%/5% gel in the mornings and adapalene 0.3% gel in the evenings for 12 weeks. Each medication tube was fitted with an electronic Medication Event Monitoring System cap (MEMS, Aardex Group, Sion, Switzerland) (to record the date and time of every opening/closing of the tube). Twenty patients were randomly assigned to receive customized twice-daily text messages instructing them to apply their morning and evening medication. The remainder of patients (N = 20), who did not receive text messages, served as control subjects. Results: Mean adherence rates for the correct application of both medications on a daily basis over 12 weeks was 33.9% for patients in the reminder group and 36.5% for patients in the control group (P = .75). Patients in both groups had similar clinical improvement of their acne. Limitations: The small sample size may limit the ability to detect differences between the study groups. Conclusions: Electronic reminders in the form of daily, customized text messages were not associated with significant differences in adherence to topical medications in patients with mild to moderate acne and had no significant effect on therapeutic response. ( J Am Acad Dermatol 2012;67:1136-42.) Key words: acne; adherence; electronic reminders; Medication Event Monitoring System; quality of life; text messages.

oor patient adherence with physicianprescribed medications is a common problem.1 This adversely affects patient outcomes and increases health care use and costs.2 This problem is even more prominent in dermatology, where earlier studies show application of a topical medication is perceived by patients as more cumbersome than taking a pill.3 Further electronic adherence monitoring has shown that dosage omission and


erratic medication timing are more prevalent than previously recognized in a number of dermatologic conditions. Recently there has been great interest in using technology such as text messaging to increase patient adherence.4,5 Recent studies indicate that patient preference for appointment reminders was via use of short message service (SMS) text messages over all other forms of communication.5-9 Textmessage reminders have shown benefit in the clinical

From the Departments of Dermatology at University of Texas Southwestern Medical Centera and University of California at Davis.b Supported by an unrestricted grant from Women’s Dermatologic Society and Mary Kay Cosmetics. Study medication was supplied in part by Stiefel Laboratories. Conflicts of interest: None declared. Accepted for publication February 27, 2012. Reprints not available from the authors.

Correspondence to: Heidi Jacobe, MD, MSCS, Department of Dermatology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9069. E-mail: [email protected] Published online April 23, 2012. 0190-9622/$36.00 Ó 2012 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2012.02.031


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care of patients with asthma,10 diabetes mellitus,11,12 any ethnic background; a clinical diagnosis of acne travelers vaccination,13 smoking cessation,14,15 and vulgaris with facial involvement for at least 6 months; increasing compliance with oral contraceptives.12 a minimum of 30 noninflammatory facial lesions More recently, Armstrong et al16 demonstrated that (open and/or closed comedones) and at least 20 daily text-message reminders increased patient’s adinflammatory lesions (papules or pustules); a score herence to daily sunscreen use by 26%. of 2 or 3 on the Investigator Global Assessment Text messaging is an attractive option to increase (IGA) scale12; and possession of a personal adherence to acne treatment mobile telephone with SMS for several reasons. Acne is a text messaging capabilities. CAPSULE SUMMARY common skin disorder affectWomen of childbearing poing up to 95% of teenagers tential were required to use Patient adherence to prescribed and young adults, a populaan acceptable birth control therapeutic regimens is generally low, tion in which text messaging measure such as abstinence, likely impeding optimal outcome; is common.6 It often requires condoms, or vaginal diahowever, automated reminders have a complex therapeutic regiphragms. Hormonal-based shown promise in increasing adherence. men and 30% to 40% of paoral contraception was only tients do not use their Our study showed no difference in allowed if treatment had been medications as prescribed, adherence between a control group and initiated at least 5 months indicating a need for meathe group that received electronic before study enrollment and sures to increase adherence.4 reminders. was given for reasons other The primary aim of this than specific treatment of Daily automated text-message study was to determine acne. Minors (\18 years) reminders may not be as effective in whether daily, automated were required to have parenincreasing adherence as previously text messages result in intal or legal guardian consent thought. creased adherence to topical to participate. Exclusion crimedications in patients with teria included: known pregmild to moderate acne compared with control subnancy, the presence of nodular or cystic acne, acne jects. In addition, we determined whether enhanced conglobata or acne fulminans, exposure to environmedication adherence resulted in measurable immental or chemical comedogenic agents, women provements in acne severity, quality of life, and with hyperandrogenism (polycystic ovarian synpatient satisfaction. We hypothesized that the text drome) or on any form of specific acne-directed messaging group would have better adherence than hormonal therapy, a history of Cushing syndrome or the control group, producing greater improvement congenital adrenal hyperplasia, and use of tanning in acne severity, quality of life, and patient beds within 4 weeks of enrollment. All female patients satisfaction. of childbearing potential were required to undergo a baseline urine pregnancy test that was repeated at METHODS each follow-up visit. Required washout periods inStudy design and population cluded: acne-specific systemic antibiotics, 2 months; This study was approved and overseen by the isotretinoin, 6 months; and topical acne medications institutional review boards of the University of Texas (prescription or over the counter), 4 weeks. Southwestern Medical Center in Dallas, TX, and Each eligible participant was assigned the same, the University of California at Davis in Davis, CA. standard antiacne treatment regimen consisting of a Healthy patients 12 to 35 years of age with mild to gentle over-the-counter daily facial cleanser moderate facial acne suitable for treatment with (Cetaphil Daily Facial Cleanser, Normal to Oily topical medications were recruited from the two skin, Galderma Laboratories, Fort Worth, TX) to be university-affiliated dermatology clinics and from used every morning, followed by the application of a advertisements posted around the medical campus standard quantity (3 pea-sized amounts) of clindaand the World Wide Web site Patients mycin/benzoyl peroxide 1%/5% topical gel (Duac, were randomized in a 1:1 ratio and assigned in a Stiefel Laboratories, Durham, NC) distributed evenly sequential manner to either receive electronic textto the entire face. For the evening application, message reminders or to serve as control subjects. patients were instructed to apply a standard amount of adapalene 0.3% gel (1 pea-sized amount) (Differin, Galderma, Ft Worth, TX) to their entire Study procedures face. If dryness or irritation resulted from this treatA total of 40 patients who met the following ment regimen, patients were instructed to buy and eligibility criteria were enrolled: male or female of d



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apply Vanicream Lite lotion (Pharmaceutical Specialties Inc, Rochester, MN) exclusively. Patients were asked to refrain from using any other facial soaps, creams, lotions, or toners and women were asked not to change their current makeup products for the duration of the study. All patients were given identical scripted verbal and written instructions on the appropriate use of their medications at the time of their enrollment. Each medication tube was fitted with a customized Medication Event Monitoring System (MEMS) cap (MEMS, Aardex Group, Sion, Switzerland) that has the ability to record the date and time of every opening/closing of the medication cap. Each opening/closing is recorded as one individual event (date/time stamp). Patients were not informed that their adherence was monitored electronically. Twenty patients were then randomized to receive daily, customized text-message reminders at a predetermined time. The World Wide Web site,, was used to create an automated and customized electronic reminder schedule for each patient in this group at their baseline visit. Individual texting schedules were chosen based on each patient’s preference and the anticipated time of each medication use. Once the schedule was created, patients in the reminder group received a customized text message twice daily (morning and evening), reminding them to apply the Duac (Stiefel Laboratories) or Differin (Galderma) gels, respectively. The content of each text message was identical for each patient and varied only by including the recipient’s first name at the start of the message. Patients in the reminder group were asked to text back a reply if and when each application was completed in an attempt to compare actual adherence (measured by MEMS caps opening/closing events) and self-reported adherence. All medication tubes and their corresponding MEMS caps were clearly labeled to avoid mix-ups. All patients had standardized digital photographs of the face and acne severity was assessed by the blinded investigator using acne lesion counts and the IGA of severity scale12 at baseline. Patients were also asked to rate the severity of their acne using the Patient Global Assessment scale.17 In addition, the Dermatology Quality of Life Index questionnaire was administered to all patients at their baseline visit. All patients were asked to return for follow-up appointments at weeks 6 and 12. At each return visit, adverse effects were recorded and efficacy assessments (acne lesion count and IGA) were performed by the blinded investigator. At week 6, all patients were resupplied with study medication.



During the 12-week exit visit, Dermatology Quality of Life Index questionnaires and patient satisfaction surveys were also administered. Dispensed medications were collected and data recorded in the MEMS caps was downloaded onto a computer by the unblinded study coordinator. Statistical analysis Adherence rates were calculated as follows: the actual number of correct MEMS cap opening/closing events for each tube (clindamycin/benzoyl peroxide tube in the morning and adapalene tube in the evening) were divided by the expected number of opening/closing events for the 12-week period. All variables were analyzed using the CochraneManteleHaenszel and analysis of variance tests to determine differences between groups. Tests were two-sided, with significance declared at the level of .05, and all calculations were computed using software (StataCorp LP, College Station, TX). Adverse events and local tolerability were summarized descriptively.

RESULTS Forty patients were enrolled in two centers and 33 (82.5%) patients completed the study including 15 patients randomized to the text group and 18 patients randomized to the control group. Seven patients failed to return for one or both of their follow-up visits and were not included in the analysis. Patient characteristics at baseline Our population included 16 male (40%) and 24 female (60%) patients. Mean age was 22.6 years (range, 14-35). The demographic and baseline disease characteristics were comparable between both groups (Table I). Patients in both groups had a similar number of inflammatory, noninflammatory, and total acne lesions and similar baseline IGA scores. Medication adherence Adherence to the prescribed topical medications decreased universally in both groups over time with slight increase in adherence in the text group before the week-6 and -12 office visit (Fig 1). Mean adherence rates for the correct application of both medications on a daily basis over 12 weeks was 33.9% for patients in the text group and 36.5% for patients in the control group (P = .5) (Table II). Self-reported adherence rates in patients receiving text messages (reflected by number of responses received from patients after each successful medication application) were 74.4%.

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Table I. Baseline patient characteristics and disease severity Age, y, mean 6 SD (range) Gender, n (%) Female Male Ethnicity, n (%) Caucasian Asian Hispanic African American Education level, n (%) In high school Graduated high school In college Graduated college In graduate school Graduate degree Baseline lesion count, mean 6 SD (range) Open comedones Closed comedones Papules Pustules Total IGA score, n (%) 0 (Clear) 1 (Almost clear) 2 (Mild) 3 (Moderate) Mean

Text, n = 19

Control, n = 21

Total, n = 40

22.8 6 5.6 (14-35)

22.5 6 5.9 (12-32)

22.68 6 5.74 (12-35)

10 (52.6) 9 (47.3)

15 (71.4) 6 (28.5)

25 (62.5) 15 (37.5)

6 1 6 6

(31.5) (5.2) (31.5) (31.5)

6 8 3 4

(28.6) (38.1) (14.2) (19.1)

12 9 9 10

(30) (22.5) (22.5) (25)

4 2 4 5 1 3

(21.1) (10.5) (21.1) (26.3) (5.2) (15.7)

8 6 2 4 1

(38.1) (28.6) (9.6) (19) (4.8) 0

12 8 6 9 2 3

(30) (20) (15) (22.5) (5) (7.5)

21 6 12.7 (3-43) 27.4 6 12.1 (12-60) 17.4 6 7.2 (9-32) 11.4 6 7.7 (0-30) 77.3 6 24.4 (47-142)

29.9 6 24.1 (7-60) 26.6 6 14.6 (5-62) 18.3 6 10.7 (10-45) 9.19 6 5.2 (0-25) 84 6 33.5 (52-150)

0 0 13 (68.4) 6 (31.6) 2.3

0 0 11 (52.4) 10 (47.6) 2.4

25.3 6 19.22 27 6 13.36 17.5 6 8.23 10.25 6 6.8 80.1 6 28.4 0 0 24 (60) 16 (40) 2.4

IGA, Investigator Global Assessment.

Table II. Adherence to study medications Text

Correct daily applications 42.8 of clindamycin/benzoyl peroxide, d (%) Correct daily applications 50.4 of adapalene, d (%) Correct daily applications 28 of both, d (%) 125.8 Self-reported adherence of patients in text group, d (%)

Fig 1. Adherence to study medications over time.

Efficacy assessments Patients in both groups showed a clinically measurable improvement in the severity of their acne. The average change in IGA score from baseline to week 12 was 1.07 for patients in the text group and




42.1 (50.1) .97


49 (58.9) .4


30 (36.5) .5




0.68 for patients in the control group (P = .37) (Table III). The proportion of patients who achieved a ‘‘clear’’ or ‘‘almost clear’’ score on the IGA scale at week 12 was 73.3% in the text group and 50% in the control group (P = .19). Similarly, patients in the text group showed a mean reduction in their total acne lesion count of 66.6% at week 12 compared with baseline, compared with a 53.4% improvement in the control group (P = .21).

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Table III. Acne severity Text


Lesion count, mean 6 SD (range)

Open comedones Closed comedones Papules Pustules Total IGA score


Wk 12

21 6 12.7 (3-43)

6.9 6 8.2 (0-34)

27.4 6 12.1 (12-60)

12.6 6 9.4 (1-30)

Change, n (%)

Lesion count, mean 6 SD (range) Baseline

14.1 (67.1) 29.9 6 24.1 (7-60) 14.8 (54)

26.6 6 14.6 (5-62)

Wk 12

Change, n (%)

13.2 6 18.3 (0-38)

16.7 (55.8)

15.3 6 10 (1-31)

11.3 (57.5)

17.4 6 7.2 (9-32) 5.2 6 5 (1-17) 12.2 (70.1) 18.3 6 10.7 (10-45) 8.1 6 9.1 (0-32) 10.2 (55.7) 11.4 6 7.7 (0-30) 1 6 1.1 (0-3) 10.4 (91.2) 9.3 6 5.4 (0-25) 2.4 6 2.4 (0-7) 6.7 (74.4) 77.3 6 24.4 (47-142) 25.8 6 19.0 (8-49) 51.4 (66.6) 84 6 33.5 (52-150) 39.1 6 34.1 (3-140) 44.9 (53.4) 2.3 1.2 1.07 2.4 1.6 0.83

IGA, Investigator Global Assessment.

Fig 2. Adherence and change in lesion counts.

When combining both the control group and the text group, patients who had a higher rate of adherence also had greater decrease in lesion count at week 12, although this was not statistically significant (R2 = .0613) (Fig 2). The mean self-reported improvement of acne severity was 55.3% for patients in the text group and 57.5% for patients in the control group. All patients reported an improvement in their acne-related quality of life (Table IV). The mean improvement in the week 12 acne-related quality of life scale was 42% from baseline for patients in the reminder group and 42.9% for control subjects. Patients in the reminder group had the most noticeable change in their acne symptoms, with a 52.3% improvement from baseline, compared with control subjects who only reported a 38.8% improvement (P = .24).

DISCUSSION To our knowledge, this is the first clinical trial to objectively measure adherence to topical medication in patients with acne. We chose a fairly simple treatment regimen using two commonly used

medications that have a solid safety and efficacy track record. We sent half of our patients a customized text message at the time of their choosing, twice a day, to ensure they received the reminders around the exact time of anticipated use. Surprisingly, we found that text messages did not increase adherence to the prescribed topical regimen in comparison with a control group that received standardized written and verbal instruction. We found patient-reported adherence was significantly higher than that objectively measured by the MEMS caps. This is consistent with other studies demonstrating patient-reported adherence is unreliable.18-20 In our study, patients were asked to reply ‘‘OK’’ to every reminder text message if they completed that particular application. Although 74% of patients replied that they applied their medication, MEMS cap monitoring indicated that the tubes were only opened 33% of the time. It is possible that patients were afraid of disappointing their physician and concealed the truth about their actual medication usage in an attempt to appear compliant. Alternatively, patients might have given a positive response at the time of the text message with the intention of applying the medication at a later date. This might explain why the MEMS cap time stamps in patients receiving text-message reminders indicated they opened their medication tubes at no particular time and independent of the time when the textmessage reminder was delivered, albeit more frequently. The largest factor impacting adherence in our study was the passage of time from the patient’s enrollment in the study. Both groups showed similar decline in mean daily and weekly adherence as the time from their baseline visit increased with increased use before follow-ups. This is similar to Feldman et al21 who showed that compliance with topical medications increased around the time of

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Table IV. Dermatology Quality of Life Index Text


Acne QoL score 6 SD (range) Baseline

Self-perception Role-social Role-emotional Symptoms Total score

14.3 14.8 13.1 11.4 55.7

6 6 6 6 6

7.8 (1-27) 7.2 (1-20) 6.9 (6-28) 7.7 (0-24) 22.6 (25-97)

25.5 21.9 24.6 23.9 96

6 6 6 6 6

Acne QoL score 6 SD (range)

Wk 12

Change (%)

4.9 (13-30) 3.8 (12-24) 5.5 (13-30) 3.4 (18-29) 15.9 (66-110)

11.2 7.1 11.5 12.5 40.3

(44) (32.5) (46.8) (52.3) (42)


12.7 13.9 12.8 14.4 53.8

6 6 6 6 6

8.4 (2-30) 6.02 (6-24) 8.5 (0-28) 6.3 (4-27) 26.8 (14-109)

Wk 12

25 20.9 24.1 23.2 94.3

6 6 6 6 6

Change (%)

6.2 (9-30) 12.3 (49.9) 5.5 (17-24) 7 (33.5) 6.4 (5-29) 11.3 (46.9) 4.1 (17-27) 8.8 (38) 18 (61-111) 40.5 (42.9)

Higher score indicates improvement. QoL, Quality of life.

doctors’ visits. Yentzer et al22 also reported that electronic reminders were not as effective as more frequent office visits in improving adherence. Therefore, increasing the frequency of office visits may be the best method to increase adherence. Taken together, our results underscore the need for objective monitoring of patient adherence in future studies. Similar to other studies, we did not observe any differences in medication adherence rates according to patient gender, age, or level of education.23,24 Surprisingly, baseline disease severity also did not appear to be a determinant of differences in medication adherence. Although text messaging is generally considered convenient and well liked by patients,12 our results indicate that people had varied responses to daily text-message reminders. Our exit questionnaire indicated that 33% of patients who received text messages started ignoring them after 2 weeks. Furthermore, 26% of patients found the text messages to be ‘‘annoying.’’ This implies text-message fatigue may limit the use of daily text messages to increase adherence. We were surprised that improvement in acne severity scores (lesion counts, IGA scores) were not associated with medication adherence. Patients with the highest adherence rates and who used their medications on a daily or almost daily basis did not have significantly lower lesion counts or better IGA scores after 12 weeks than patients who used the prescribed medications 3 to 4 times weekly. This raises the question whether daily applications of antiacne medications are in fact necessary for disease control or whether thrice-weekly applications is enough to produce the same results. This requires further study, because less frequent application may result in fewer medication-related side effects and a higher patient acceptance. In summary, we found that text messaging may not be as effective in increasing adherence or acceptable to patients as is generally thought,

particularly in adolescents or young adults receiving multiple reminders daily. However, our results also indicate absolute adherence (at least for patients with mild to moderate acne) might not be necessary for acceptable improvement in acne. This warrants further investigation. Our results indicate that the best method to increase adherence might be more frequent office visits.

Limitations This was a small study of only 40 patients. It is likely that a larger study might detect measurable differences in adherence rates and clinical outcome. It is also possible that a twice-daily text messaging schedule was too frequent and less frequent reminders may be more acceptable and efficacious. The adherence rate measured by the MEMS caps in this study recorded the total number of opening and closing events of the study tubes and may not be representative of actual study drug application. We would like to thank Lynda Leyo and Natasha Klimas for their assistance with this project. REFERENCES 1. Berg JS, Dischler J, Wagner DJ, Raia JJ, Palmer-Shevlin N. Medication compliance: a healthcare problem. Ann Pharmacother 1993;27(Suppl):S1-24. 2. Gold DT. Medication adherence: a challenge for patients with postmenopausal osteoporosis and other chronic illnesses. J Manag Care Pharm 2006;12(Suppl):S20-5, quiz S26-8. 3. Lee IA, Maibach HI. Pharmionics in dermatology: a review of topical medication adherence. Am J Clin Dermatol 2006;7: 231-6. 4. Zaghloul SS, Cunliffe WJ, Goodfield MJ. Objective assessment of compliance with treatments in acne. Br J Dermatol 2005; 152:1015-21. 5. Cohen CE, Coyne KM, Mandalia S, Waters AM, Sullivan AK. Time to use text reminders in genitourinary medicine clinics. Int J STD AIDS 2008;19:12-3. 6. Downer SR, Meara JG, Da Costa AC, Sethuraman K. SMS text messaging improves outpatient attendance. Aust Health Rev 2006;30:389-96. 7. Leong KC, Chen WS, Leong KW, Mastura I, Mimi O, Sheikh MA, et al. The use of text messaging to improve attendance in

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primary care: a randomized controlled trial. Fam Pract 2006;23: 699-705. Geraghty M, Glynn F, Amin M, Kinsella J. Patient mobile telephone ‘text’ reminder: a novel way to reduce non-attendance at the ENT out-patient clinic. J Laryngol Otol 2008;122:296-8. Chen ZW, Fang LZ, Chen LY, Dai HL. Comparison of an SMS text messaging and phone reminder to improve attendance at a health promotion center: a randomized controlled trial. J Zhejiang Univ Sci B 2008;9:34-8. Ostojic V, Cvoriscec B, Ostojic SB, Reznikoff D, Stipic-Markovic A, Tudjman Z. Improving asthma control through telemedicine: a study of short-message service. Telemed J E Health 2005;11:28-35. Ferrer-Roca O, Cardenas A, Diaz-Cardama A, Pulido P. Mobile phone text messaging in the management of diabetes. J Telemed Telecare 2004;10:282-5. Franklin VL, Greene A, Waller A, Greene SA, Pagliari C. Patients’ engagement with ‘‘Sweet Talk’’ea text messaging support system for young people with diabetes. J Med Internet Res 2008;10:e20. Vilella A, Bayas JM, Diaz MT, Guinovart C, Diez C, Simo D, et al. The role of mobile phones in improving vaccination rates in travelers. Prev Med 2004;38:503-9. Rodgers A, Corbett T, Bramley D, Riddell T, Wills M, Lin RB, et al. Do u smoke after txt? Results of a randomized trial of smoking cessation using mobile phone text messaging. Tob Control 2005;14:255-61. Brendryen H, Kraft P. Happy ending: a randomized controlled trial of a digital multi-media smoking cessation intervention. Addiction 2008;103:478-86. Armstrong AW, Watson AJ, Makredes M, Frangos JE, Kimball AB, Kvedar JC. Text-message reminders to improve sunscreen











use: a randomized, controlled trial using electronic monitoring. Arch Dermatol 2009;145:1230-6. Maly P, Thall A, Petryniak B, Rogers CE, Smith PL, Marks RM, et al. The alpha(1,3)fucosyltransferase Fuc-TVII controls leukocyte trafficking through an essential role in L-, E-, and P-selectin ligand biosynthesis. Cell 1996;86:643-53. Bell DJ, Wootton D, Mukaka M, Montgomery J, Kayange N, Chimpeni P, et al. Measurement of adherence, drug concentrations and the effectiveness of artemether-lumefantrine, chlorproguanil-dapsone or sulphadoxine-pyrimethamine in the treatment of uncomplicated malaria in Malawi. Malar J 2009;8:204. Muller AD, Bode S, Myer L, Roux P, von Steinbuchel N. Electronic measurement of adherence to pediatric antiretroviral therapy in South Africa. Pediatr Infect Dis J 2008;27:257-62. Carroll CL, Feldman SR, Camacho FT, Manuel JC, Balkrishnan R. Adherence to topical therapy decreases during the course of an 8-week psoriasis clinical trial: commonly used methods of measuring adherence to topical therapy overestimate actual use. J Am Acad Dermatol 2004;51:212-6. Feldman SR, Camacho FT, Krejci-Manwaring J, Carroll CL, Balkrishnan R. Adherence to topical therapy increases around the time of office visits. J Am Acad Dermatol 2007;57:81-3. Yentzer BA, Gosnell AL, Clark AR, Pearce DJ, Balkrishnan R, Camacho FT, et al. A randomized controlled pilot study of strategies to increase adherence in teenagers with acne vulgaris. J Am Acad Dermatol 2011;64:793-5. Wong MC, Jiang JY, Griffiths SM. Factors associated with compliance to thiazide diuretics among 8551 Chinese patients. J Clin Pharm Ther 2011;36:179-86. Mahfouz EM, Awadalla HI. Compliance to diabetes self-management in rural El-Mina, Egypt. Cent Eur J Public Health 2011;19:35-41.