Nicolls SJ, Puri S, Anderson, T, et al. Effect of evolocumab on progression of coronary disease in statin-treated patients. The GLAGOV randomized clinical trial. JAMA 2016;316:2372–84.

To Download a PDF of the Full Article:

Click Here

Study Overview

Objective. To determine if evolocumab, a PCSK9 inhibitor, affects the progression of coronary artery disease in patients treated with statins.

Design. Multicenter, international, double-blind, placebo-controlled, randomized clinical trial.

Setting and participants. 197 community and academic hospitals worldwide enrolled 978 participants who underwent serial intravascular ultrasounds (IVUS) to measure their burden of coronary atherosclerosis. A total of 2628 patients were screened. Patients were considered for inclusion if they were 18 years of age or older and had at least 1 coronary artery stenosis of at least 20% on a clinically indicated catheterization. Additionally, the target vessel had to meet IVUS imaging quality and visibility standards. Participants were required to have been on stable statin therapy for at least 4 weeks with an LDL level of > 80 mg/dL or between 60–80 mg/dL with either 1 major or 3 minor cardiovascular risk factors. Major risk factors were noncoronary atherosclerotic disease, myocardial infarction (MI) or hospitalization for unstable angina within the past 2 years, or type 2 diabetes. Minor risk factors included current tobacco use, hypertension, low HDL-C levels, family history of early coronary disease, hsCRP level of 2 mg/L or greater, and age older than 50 years for men and 55 years for women. Patients with uncontrolled hypertension, uncontrolled diabetes, heart failure, renal insufficiency, or liver disease were excluded.

Intervention. Patients were randomized to either treatment with monthly subcutaneous injections of 420 mg evolocumab or placebo injections for 76 weeks. Participants attended 7 follow-up visits during the study period and then underwent repeat IVUS imaging at the 78th week. Research staff, who were blinded to both treatment status and imaging sequence, collected and assessed target vessel measurements, including the vessel lumen and external elastic membrane dimensions. IVUS imaging has been used in numerous clinical studies and has been shown to be accurate and reliable [1].

Main outcome measures. The primary outcome was the target artery change in percent atheroma volume (PAV) from baseline to week 78. PAV was calculated from IVUS measurements. Nominal change in PAV was then determined by calculating the difference of the PAV at baseline and at week 78.

The secondary measure was the normalized total atheroma volume (TAV). TAV addresses variability in the length of vessel segments and the number of images collected during IVUS catheter pullback. The nominal change in TAV was then determined by the difference at baseline and at week 78.

Additional secondary efficacy endpoints included number of patients with regression of plaque and change in lipid parameters. Safety outcomes were investigated through evaluation of the incidence of adjudicated clinical events, including all-cause mortality, cardiovascular death, MI, unstable angina requiring hospitalization, coronary revascularization, stroke, transient ischemic attack, and heart failure requiring hospitalization. Post-hoc analysis compared baseline LDL-C level and change in PAV and regression of PAV. The association between LDL lowering and plaque progression was also assessed post hoc.

IVUS measurements were evaluated as least squares means. Comparison of treatment groups was conducted using analysis of covariance on rank transformed data that accounted for baseline value and geographic location. Investigators used a step-down statistical procedure to evaluate primary and secondary endpoints. The statistical model accounted for confounders such as baseline LDL-C, baseline PAV, intensity of statin therapy, geographic region, age, and sex.

Main results. 484 participants were randomized to the evolocumab group and 484 to the placebo group, and 423 participants in both groups completed both baseline and follow-up IVUS imaging. Treatment and control groups contained participants matched for age, gender, ethnicity, cardiovascular risk factors, and baseline medication use, including lipid-lowering agents, ACE inhibitors, ARBs, beta-blockers, and antiplatelet therapies. Both groups consisted of a majority of white (93.4% in placebo and 94.2% in treatment) males (72.3% in placebo and 72.1% in treatment). Approximately 80% of participants had hypertension (83.7% in placebo and 82.2% in treatment), about 35% had prior MIs (35.3% in placebo and 34.9% in treatment), and roughly a fifth of participants had diabetes (21.5% in placebo and 20.2% in treatment). At baseline 98.6% of participants were treated with statins, with 58.9% on high-intensity therapy and 39.4% on moderate-intensity. Mean LDL-C level at baseline was 92.5 (SD, 27.2) mg/dL.

After 76 weeks of treatment, mean LDL-C level in the placebo group was 93.0 mg/dL and 36.6 mg/dL in the treatment group, which corresponds to a 0.2 mg/dL increase in the placebo group and a 56.3 mg/dL reduction in the treatment group. The change in LDL-C level was statistically significant (P < 0.001).

Placebo group participants had no significant change in PAV (0.05%, P = 0.78), but the evolocumab group experienced a 0.95% decrease from baseline (P < 0.001). Similarly, the placebo group had no change in TAV from baseline (–0.9 mm³, P = 0.45), but the treatment group had a 5.8 mm³ reduction in TAV from baseline (P < 0.001). The treatment group had a greater proportion of patients who experienced PAV regression (64.3% vs. 47.3%, P < 0.001) and TAV regression (61.5% vs. 48.9%, P < 0.001).

Subgroup analysis did not demonstrate a significant association between change in PAV and specific study participant characteristics (eg, age, gender, ethnicity).

Post-hoc analysis using local regression (LOESS) curve revealed a linear relationship between achieved LDL-C level and change in PAV for LDL-C levels from 110 mg/dL to 20 mg/dL.

The treatment group did not exhibit a significant increase in adverse drug events, which included injection site reactions, myalgias, neurocognitive events, and incidence of diabetes. There was no significant difference in adverse cardiovascular outcomes between groups; however, there were numerically fewer nonfatal MIs and coronary revascularizations in the treatment group.

Conclusion. The use of evolocumab in statin-treated patients resulted in greater reduction of PAV than use of statins alone.

Commentary

Evolocumab is a monoclonal antibody that inhibits pro-protein convertase subtilisin-kexin type 9 (PCSK9), which is involved in LDL-C receptor recycling. By reducing removal of LDL-C receptors, evolocumab amplifies LDL-C clearance and has been shown to reduce LDL-C levels by approximately 61% from baseline with 12 weeks oftreatment [2]. Studies have shown that the lipid-lowering potential of evolocumab is superior to statins alone and to combination therapy with statins and ezetimibe [2]. Furthermore, PCSK9 inhibitors have been effective at LDL-lowering in patients who failed or could not tolerate standard of care therapy with statins and ezetimibe [3,4]. PCSK9 inhibitors hold great promise for reducing morbidity and mortality of cardiovascular disease; however, LDL-lowering is not equivalent to improved clinical outcomes.

The GLAGOV study moves toward demonstration of the clinical benefit of evolocumab. The study shows that combined therapy with statins and evolocumab, versus statins alone, not only achieves better stability of atherosclerotic plaque dimensions but actually results in regression of plaque size. In the study, plaque burden is extrapolated from vessel measurements obtained through IVUS, and nominal changes in PAV and TAV serve as markers for atherosclerosis, but these surrogates cannot be equated to a reduction in cardiovascular events. The GLAGOV trial does explore clinical outcomes such as MI, stroke, unstable angina, coronary revascularization, and death; however, the study is not powered to evaluate the statistical significance of these events. We await sufficiently powered phase 3 clinical trials to determine the clinical benefits of PCSK9 inhibitors on cardiovascular disease.

The GLAGOV trial has several strengths, including its design as an international, double-blind, placebo-controlled, randomized clinical trial. The intervention is simple and the outcomes are clearly defined. The statistical assessment yields significant results. Nonetheless, there are multiple limitations to the study. The lead author has received research support from Amgen, the maker of evolocumab. Amgen also participated in study design and maintenance of trial databases; however, data analysis was conducted by an independent statistician. Additionally, the majority of study participants were white males with very few minority patients despite inclusion of study sites around the globe. The homogeneity of the study cohort makes the data difficult to generalize to a larger population. Similarly, patients who lacked a clinical indication for coronary catheterization and those with uncontrolled diabetes, hypertension, and heart failure were excluded, which further limits application of this study to many patients with atherosclerosis. Another limitation is study attrition; only 87% of participants completed the 78-week IVUS and were included in the data analysis, and results may have differed if those lost to follow-up had completed the trial. Furthermore, study duration was limited to 76 weeks and the magnitude and durability of study outcomes after this time point remain unknown.

Applications for Clinical Practice

Reduction in PAV and TAV are surrogate endpoints and are not indicative of a clinical benefit. Nonetheless, the GLAGOV study demonstrates that evolocumab, when used in conjunction with statins, can promote regression of atherosclerosis greater than treatment with statins alone. More studies are needed to evaluate a clinical benefit of adding evolocumab to the regularly used arsenal of lipid-lowering therapies for the treatment of atherosclerosis. Furthermore, cost-effectiveness of evolocumab has not been shown. In 2015 the yearly wholesale price of evolcumab was $14,350. A cost-effectiveness analysis based on this price estimates that treatment of atherosclerotic coronary vascular disease with evolocumab has a cost of $414,000 per quality-adjusted life year [5]. Evolocumab is well tolerated, but additional studies for cardiovascular and mortality outcomes are needed before it can be considered part of the standard of treatment for coronary artery disease.

—Lauren Brooks, MD, University of Maryland School of Medicine, Baltimore, MD

References

1. Nicholls SJ, Hsu A, Wolski K, et al. Intravascular ultrasound-derived measures of coronary atherosclerotic plaque burden and clinical outcome. J Am Coll Cardiol 2010;55:2399–407.

2. Sabatine MS, Giugliano RP, Wiviolt SD, et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med 2015;372:1500–9.

3. Giugliano RP, Sabatine MS. Are PCSK9 inhibitors the next breakthrough in the cardiovascular field. J Am Coll Cardiol 2015;65:2639–51.

4. Stroes E, Colquhoun D, Sullivan D, et al. Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance: the GAUSS-2 randomized, placebo-controlled phase 3 clinical trial of evolocumab. J Am Coll Cardiol 2014;63:2541–8.

5. Dhruv KS, Moran AE, Coxson PG, et al. Cost-effectiveness of PCSK9 inhibitor therapy in patients with heterozygous familial hypercholesterolemia or atherosclerotic coronary artery disease. JAMA 2016;316:743–53.

Nicolls SJ, Puri S, Anderson, T, et al. Effect of evolocumab on progression of coronary disease in statin-treated patients. The GLAGOV randomized clinical trial. JAMA 2016;316:2372–84.

To Download a PDF of the Full Article:

Click Here

Study Overview

Objective. To determine if evolocumab, a PCSK9 inhibitor, affects the progression of coronary artery disease in patients treated with statins.

Design. Multicenter, international, double-blind, placebo-controlled, randomized clinical trial.

Setting and participants. 197 community and academic hospitals worldwide enrolled 978 participants who underwent serial intravascular ultrasounds (IVUS) to measure their burden of coronary atherosclerosis. A total of 2628 patients were screened. Patients were considered for inclusion if they were 18 years of age or older and had at least 1 coronary artery stenosis of at least 20% on a clinically indicated catheterization. Additionally, the target vessel had to meet IVUS imaging quality and visibility standards. Participants were required to have been on stable statin therapy for at least 4 weeks with an LDL level of > 80 mg/dL or between 60–80 mg/dL with either 1 major or 3 minor cardiovascular risk factors. Major risk factors were noncoronary atherosclerotic disease, myocardial infarction (MI) or hospitalization for unstable angina within the past 2 years, or type 2 diabetes. Minor risk factors included current tobacco use, hypertension, low HDL-C levels, family history of early coronary disease, hsCRP level of 2 mg/L or greater, and age older than 50 years for men and 55 years for women. Patients with uncontrolled hypertension, uncontrolled diabetes, heart failure, renal insufficiency, or liver disease were excluded.

Intervention. Patients were randomized to either treatment with monthly subcutaneous injections of 420 mg evolocumab or placebo injections for 76 weeks. Participants attended 7 follow-up visits during the study period and then underwent repeat IVUS imaging at the 78th week. Research staff, who were blinded to both treatment status and imaging sequence, collected and assessed target vessel measurements, including the vessel lumen and external elastic membrane dimensions. IVUS imaging has been used in numerous clinical studies and has been shown to be accurate and reliable [1].

Main outcome measures. The primary outcome was the target artery change in percent atheroma volume (PAV) from baseline to week 78. PAV was calculated from IVUS measurements. Nominal change in PAV was then determined by calculating the difference of the PAV at baseline and at week 78.

The secondary measure was the normalized total atheroma volume (TAV). TAV addresses variability in the length of vessel segments and the number of images collected during IVUS catheter pullback. The nominal change in TAV was then determined by the difference at baseline and at week 78.

Additional secondary efficacy endpoints included number of patients with regression of plaque and change in lipid parameters. Safety outcomes were investigated through evaluation of the incidence of adjudicated clinical events, including all-cause mortality, cardiovascular death, MI, unstable angina requiring hospitalization, coronary revascularization, stroke, transient ischemic attack, and heart failure requiring hospitalization. Post-hoc analysis compared baseline LDL-C level and change in PAV and regression of PAV. The association between LDL lowering and plaque progression was also assessed post hoc.

IVUS measurements were evaluated as least squares means. Comparison of treatment groups was conducted using analysis of covariance on rank transformed data that accounted for baseline value and geographic location. Investigators used a step-down statistical procedure to evaluate primary and secondary endpoints. The statistical model accounted for confounders such as baseline LDL-C, baseline PAV, intensity of statin therapy, geographic region, age, and sex.

Main results. 484 participants were randomized to the evolocumab group and 484 to the placebo group, and 423 participants in both groups completed both baseline and follow-up IVUS imaging. Treatment and control groups contained participants matched for age, gender, ethnicity, cardiovascular risk factors, and baseline medication use, including lipid-lowering agents, ACE inhibitors, ARBs, beta-blockers, and antiplatelet therapies. Both groups consisted of a majority of white (93.4% in placebo and 94.2% in treatment) males (72.3% in placebo and 72.1% in treatment). Approximately 80% of participants had hypertension (83.7% in placebo and 82.2% in treatment), about 35% had prior MIs (35.3% in placebo and 34.9% in treatment), and roughly a fifth of participants had diabetes (21.5% in placebo and 20.2% in treatment). At baseline 98.6% of participants were treated with statins, with 58.9% on high-intensity therapy and 39.4% on moderate-intensity. Mean LDL-C level at baseline was 92.5 (SD, 27.2) mg/dL.

After 76 weeks of treatment, mean LDL-C level in the placebo group was 93.0 mg/dL and 36.6 mg/dL in the treatment group, which corresponds to a 0.2 mg/dL increase in the placebo group and a 56.3 mg/dL reduction in the treatment group. The change in LDL-C level was statistically significant (P < 0.001).

Placebo group participants had no significant change in PAV (0.05%, P = 0.78), but the evolocumab group experienced a 0.95% decrease from baseline (P < 0.001). Similarly, the placebo group had no change in TAV from baseline (–0.9 mm³, P = 0.45), but the treatment group had a 5.8 mm³ reduction in TAV from baseline (P < 0.001). The treatment group had a greater proportion of patients who experienced PAV regression (64.3% vs. 47.3%, P < 0.001) and TAV regression (61.5% vs. 48.9%, P < 0.001).

Subgroup analysis did not demonstrate a significant association between change in PAV and specific study participant characteristics (eg, age, gender, ethnicity).

Post-hoc analysis using local regression (LOESS) curve revealed a linear relationship between achieved LDL-C level and change in PAV for LDL-C levels from 110 mg/dL to 20 mg/dL.

The treatment group did not exhibit a significant increase in adverse drug events, which included injection site reactions, myalgias, neurocognitive events, and incidence of diabetes. There was no significant difference in adverse cardiovascular outcomes between groups; however, there were numerically fewer nonfatal MIs and coronary revascularizations in the treatment group.

Conclusion. The use of evolocumab in statin-treated patients resulted in greater reduction of PAV than use of statins alone.

Commentary

Evolocumab is a monoclonal antibody that inhibits pro-protein convertase subtilisin-kexin type 9 (PCSK9), which is involved in LDL-C receptor recycling. By reducing removal of LDL-C receptors, evolocumab amplifies LDL-C clearance and has been shown to reduce LDL-C levels by approximately 61% from baseline with 12 weeks oftreatment [2]. Studies have shown that the lipid-lowering potential of evolocumab is superior to statins alone and to combination therapy with statins and ezetimibe [2]. Furthermore, PCSK9 inhibitors have been effective at LDL-lowering in patients who failed or could not tolerate standard of care therapy with statins and ezetimibe [3,4]. PCSK9 inhibitors hold great promise for reducing morbidity and mortality of cardiovascular disease; however, LDL-lowering is not equivalent to improved clinical outcomes.

The GLAGOV study moves toward demonstration of the clinical benefit of evolocumab. The study shows that combined therapy with statins and evolocumab, versus statins alone, not only achieves better stability of atherosclerotic plaque dimensions but actually results in regression of plaque size. In the study, plaque burden is extrapolated from vessel measurements obtained through IVUS, and nominal changes in PAV and TAV serve as markers for atherosclerosis, but these surrogates cannot be equated to a reduction in cardiovascular events. The GLAGOV trial does explore clinical outcomes such as MI, stroke, unstable angina, coronary revascularization, and death; however, the study is not powered to evaluate the statistical significance of these events. We await sufficiently powered phase 3 clinical trials to determine the clinical benefits of PCSK9 inhibitors on cardiovascular disease.

The GLAGOV trial has several strengths, including its design as an international, double-blind, placebo-controlled, randomized clinical trial. The intervention is simple and the outcomes are clearly defined. The statistical assessment yields significant results. Nonetheless, there are multiple limitations to the study. The lead author has received research support from Amgen, the maker of evolocumab. Amgen also participated in study design and maintenance of trial databases; however, data analysis was conducted by an independent statistician. Additionally, the majority of study participants were white males with very few minority patients despite inclusion of study sites around the globe. The homogeneity of the study cohort makes the data difficult to generalize to a larger population. Similarly, patients who lacked a clinical indication for coronary catheterization and those with uncontrolled diabetes, hypertension, and heart failure were excluded, which further limits application of this study to many patients with atherosclerosis. Another limitation is study attrition; only 87% of participants completed the 78-week IVUS and were included in the data analysis, and results may have differed if those lost to follow-up had completed the trial. Furthermore, study duration was limited to 76 weeks and the magnitude and durability of study outcomes after this time point remain unknown.

Applications for Clinical Practice

Reduction in PAV and TAV are surrogate endpoints and are not indicative of a clinical benefit. Nonetheless, the GLAGOV study demonstrates that evolocumab, when used in conjunction with statins, can promote regression of atherosclerosis greater than treatment with statins alone. More studies are needed to evaluate a clinical benefit of adding evolocumab to the regularly used arsenal of lipid-lowering therapies for the treatment of atherosclerosis. Furthermore, cost-effectiveness of evolocumab has not been shown. In 2015 the yearly wholesale price of evolcumab was $14,350. A cost-effectiveness analysis based on this price estimates that treatment of atherosclerotic coronary vascular disease with evolocumab has a cost of $414,000 per quality-adjusted life year [5]. Evolocumab is well tolerated, but additional studies for cardiovascular and mortality outcomes are needed before it can be considered part of the standard of treatment for coronary artery disease.

—Lauren Brooks, MD, University of Maryland School of Medicine, Baltimore, MD

References

1. Nicholls SJ, Hsu A, Wolski K, et al. Intravascular ultrasound-derived measures of coronary atherosclerotic plaque burden and clinical outcome. J Am Coll Cardiol 2010;55:2399–407.

2. Sabatine MS, Giugliano RP, Wiviolt SD, et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med 2015;372:1500–9.

3. Giugliano RP, Sabatine MS. Are PCSK9 inhibitors the next breakthrough in the cardiovascular field. J Am Coll Cardiol 2015;65:2639–51.

4. Stroes E, Colquhoun D, Sullivan D, et al. Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance: the GAUSS-2 randomized, placebo-controlled phase 3 clinical trial of evolocumab. J Am Coll Cardiol 2014;63:2541–8.

5. Dhruv KS, Moran AE, Coxson PG, et al. Cost-effectiveness of PCSK9 inhibitor therapy in patients with heterozygous familial hypercholesterolemia or atherosclerotic coronary artery disease. JAMA 2016;316:743–53.

Nicolls SJ, Puri S, Anderson, T, et al. Effect of evolocumab on progression of coronary disease in statin-treated patients. The GLAGOV randomized clinical trial. JAMA 2016;316:2372–84.

To Download a PDF of the Full Article:

Click Here

Study Overview

Objective. To determine if evolocumab, a PCSK9 inhibitor, affects the progression of coronary artery disease in patients treated with statins.

Design. Multicenter, international, double-blind, placebo-controlled, randomized clinical trial.

Setting and participants. 197 community and academic hospitals worldwide enrolled 978 participants who underwent serial intravascular ultrasounds (IVUS) to measure their burden of coronary atherosclerosis. A total of 2628 patients were screened. Patients were considered for inclusion if they were 18 years of age or older and had at least 1 coronary artery stenosis of at least 20% on a clinically indicated catheterization. Additionally, the target vessel had to meet IVUS imaging quality and visibility standards. Participants were required to have been on stable statin therapy for at least 4 weeks with an LDL level of > 80 mg/dL or between 60–80 mg/dL with either 1 major or 3 minor cardiovascular risk factors. Major risk factors were noncoronary atherosclerotic disease, myocardial infarction (MI) or hospitalization for unstable angina within the past 2 years, or type 2 diabetes. Minor risk factors included current tobacco use, hypertension, low HDL-C levels, family history of early coronary disease, hsCRP level of 2 mg/L or greater, and age older than 50 years for men and 55 years for women. Patients with uncontrolled hypertension, uncontrolled diabetes, heart failure, renal insufficiency, or liver disease were excluded.

Intervention. Patients were randomized to either treatment with monthly subcutaneous injections of 420 mg evolocumab or placebo injections for 76 weeks. Participants attended 7 follow-up visits during the study period and then underwent repeat IVUS imaging at the 78th week. Research staff, who were blinded to both treatment status and imaging sequence, collected and assessed target vessel measurements, including the vessel lumen and external elastic membrane dimensions. IVUS imaging has been used in numerous clinical studies and has been shown to be accurate and reliable [1].

Main outcome measures. The primary outcome was the target artery change in percent atheroma volume (PAV) from baseline to week 78. PAV was calculated from IVUS measurements. Nominal change in PAV was then determined by calculating the difference of the PAV at baseline and at week 78.

The secondary measure was the normalized total atheroma volume (TAV). TAV addresses variability in the length of vessel segments and the number of images collected during IVUS catheter pullback. The nominal change in TAV was then determined by the difference at baseline and at week 78.

Additional secondary efficacy endpoints included number of patients with regression of plaque and change in lipid parameters. Safety outcomes were investigated through evaluation of the incidence of adjudicated clinical events, including all-cause mortality, cardiovascular death, MI, unstable angina requiring hospitalization, coronary revascularization, stroke, transient ischemic attack, and heart failure requiring hospitalization. Post-hoc analysis compared baseline LDL-C level and change in PAV and regression of PAV. The association between LDL lowering and plaque progression was also assessed post hoc.

IVUS measurements were evaluated as least squares means. Comparison of treatment groups was conducted using analysis of covariance on rank transformed data that accounted for baseline value and geographic location. Investigators used a step-down statistical procedure to evaluate primary and secondary endpoints. The statistical model accounted for confounders such as baseline LDL-C, baseline PAV, intensity of statin therapy, geographic region, age, and sex.

Main results. 484 participants were randomized to the evolocumab group and 484 to the placebo group, and 423 participants in both groups completed both baseline and follow-up IVUS imaging. Treatment and control groups contained participants matched for age, gender, ethnicity, cardiovascular risk factors, and baseline medication use, including lipid-lowering agents, ACE inhibitors, ARBs, beta-blockers, and antiplatelet therapies. Both groups consisted of a majority of white (93.4% in placebo and 94.2% in treatment) males (72.3% in placebo and 72.1% in treatment). Approximately 80% of participants had hypertension (83.7% in placebo and 82.2% in treatment), about 35% had prior MIs (35.3% in placebo and 34.9% in treatment), and roughly a fifth of participants had diabetes (21.5% in placebo and 20.2% in treatment). At baseline 98.6% of participants were treated with statins, with 58.9% on high-intensity therapy and 39.4% on moderate-intensity. Mean LDL-C level at baseline was 92.5 (SD, 27.2) mg/dL.

After 76 weeks of treatment, mean LDL-C level in the placebo group was 93.0 mg/dL and 36.6 mg/dL in the treatment group, which corresponds to a 0.2 mg/dL increase in the placebo group and a 56.3 mg/dL reduction in the treatment group. The change in LDL-C level was statistically significant (P < 0.001).

Placebo group participants had no significant change in PAV (0.05%, P = 0.78), but the evolocumab group experienced a 0.95% decrease from baseline (P < 0.001). Similarly, the placebo group had no change in TAV from baseline (–0.9 mm³, P = 0.45), but the treatment group had a 5.8 mm³ reduction in TAV from baseline (P < 0.001). The treatment group had a greater proportion of patients who experienced PAV regression (64.3% vs. 47.3%, P < 0.001) and TAV regression (61.5% vs. 48.9%, P < 0.001).

Subgroup analysis did not demonstrate a significant association between change in PAV and specific study participant characteristics (eg, age, gender, ethnicity).

Post-hoc analysis using local regression (LOESS) curve revealed a linear relationship between achieved LDL-C level and change in PAV for LDL-C levels from 110 mg/dL to 20 mg/dL.

The treatment group did not exhibit a significant increase in adverse drug events, which included injection site reactions, myalgias, neurocognitive events, and incidence of diabetes. There was no significant difference in adverse cardiovascular outcomes between groups; however, there were numerically fewer nonfatal MIs and coronary revascularizations in the treatment group.

Conclusion. The use of evolocumab in statin-treated patients resulted in greater reduction of PAV than use of statins alone.

Commentary

Evolocumab is a monoclonal antibody that inhibits pro-protein convertase subtilisin-kexin type 9 (PCSK9), which is involved in LDL-C receptor recycling. By reducing removal of LDL-C receptors, evolocumab amplifies LDL-C clearance and has been shown to reduce LDL-C levels by approximately 61% from baseline with 12 weeks oftreatment [2]. Studies have shown that the lipid-lowering potential of evolocumab is superior to statins alone and to combination therapy with statins and ezetimibe [2]. Furthermore, PCSK9 inhibitors have been effective at LDL-lowering in patients who failed or could not tolerate standard of care therapy with statins and ezetimibe [3,4]. PCSK9 inhibitors hold great promise for reducing morbidity and mortality of cardiovascular disease; however, LDL-lowering is not equivalent to improved clinical outcomes.

The GLAGOV study moves toward demonstration of the clinical benefit of evolocumab. The study shows that combined therapy with statins and evolocumab, versus statins alone, not only achieves better stability of atherosclerotic plaque dimensions but actually results in regression of plaque size. In the study, plaque burden is extrapolated from vessel measurements obtained through IVUS, and nominal changes in PAV and TAV serve as markers for atherosclerosis, but these surrogates cannot be equated to a reduction in cardiovascular events. The GLAGOV trial does explore clinical outcomes such as MI, stroke, unstable angina, coronary revascularization, and death; however, the study is not powered to evaluate the statistical significance of these events. We await sufficiently powered phase 3 clinical trials to determine the clinical benefits of PCSK9 inhibitors on cardiovascular disease.

The GLAGOV trial has several strengths, including its design as an international, double-blind, placebo-controlled, randomized clinical trial. The intervention is simple and the outcomes are clearly defined. The statistical assessment yields significant results. Nonetheless, there are multiple limitations to the study. The lead author has received research support from Amgen, the maker of evolocumab. Amgen also participated in study design and maintenance of trial databases; however, data analysis was conducted by an independent statistician. Additionally, the majority of study participants were white males with very few minority patients despite inclusion of study sites around the globe. The homogeneity of the study cohort makes the data difficult to generalize to a larger population. Similarly, patients who lacked a clinical indication for coronary catheterization and those with uncontrolled diabetes, hypertension, and heart failure were excluded, which further limits application of this study to many patients with atherosclerosis. Another limitation is study attrition; only 87% of participants completed the 78-week IVUS and were included in the data analysis, and results may have differed if those lost to follow-up had completed the trial. Furthermore, study duration was limited to 76 weeks and the magnitude and durability of study outcomes after this time point remain unknown.

Applications for Clinical Practice

Reduction in PAV and TAV are surrogate endpoints and are not indicative of a clinical benefit. Nonetheless, the GLAGOV study demonstrates that evolocumab, when used in conjunction with statins, can promote regression of atherosclerosis greater than treatment with statins alone. More studies are needed to evaluate a clinical benefit of adding evolocumab to the regularly used arsenal of lipid-lowering therapies for the treatment of atherosclerosis. Furthermore, cost-effectiveness of evolocumab has not been shown. In 2015 the yearly wholesale price of evolcumab was $14,350. A cost-effectiveness analysis based on this price estimates that treatment of atherosclerotic coronary vascular disease with evolocumab has a cost of $414,000 per quality-adjusted life year [5]. Evolocumab is well tolerated, but additional studies for cardiovascular and mortality outcomes are needed before it can be considered part of the standard of treatment for coronary artery disease.

—Lauren Brooks, MD, University of Maryland School of Medicine, Baltimore, MD

References

1. Nicholls SJ, Hsu A, Wolski K, et al. Intravascular ultrasound-derived measures of coronary atherosclerotic plaque burden and clinical outcome. J Am Coll Cardiol 2010;55:2399–407.

2. Sabatine MS, Giugliano RP, Wiviolt SD, et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med 2015;372:1500–9.

3. Giugliano RP, Sabatine MS. Are PCSK9 inhibitors the next breakthrough in the cardiovascular field. J Am Coll Cardiol 2015;65:2639–51.

4. Stroes E, Colquhoun D, Sullivan D, et al. Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance: the GAUSS-2 randomized, placebo-controlled phase 3 clinical trial of evolocumab. J Am Coll Cardiol 2014;63:2541–8.

5. Dhruv KS, Moran AE, Coxson PG, et al. Cost-effectiveness of PCSK9 inhibitor therapy in patients with heterozygous familial hypercholesterolemia or atherosclerotic coronary artery disease. JAMA 2016;316:743–53.

Prescription drug spending for those with employer-sponsored insurance increased by 3.8% in 2016, compared with a rise of 5.2% in 2015, according to pharmacy benefits manager Express Scripts.

Commercial plans managed by Express Scripts saw the cost of prescription drugs rise by 2.5% per person, while utilization was up by 1.3%, which adds up to the 3.8% overall increase. That represents a 27% drop from 2015, when drug use rose 2.0% and costs went up by 3.2%, Express Scripts said in its “2016 Drug Trend Report.”

[email protected]

Prescription drug spending for those with employer-sponsored insurance increased by 3.8% in 2016, compared with a rise of 5.2% in 2015, according to pharmacy benefits manager Express Scripts.

Commercial plans managed by Express Scripts saw the cost of prescription drugs rise by 2.5% per person, while utilization was up by 1.3%, which adds up to the 3.8% overall increase. That represents a 27% drop from 2015, when drug use rose 2.0% and costs went up by 3.2%, Express Scripts said in its “2016 Drug Trend Report.”

[email protected]

Prescription drug spending for those with employer-sponsored insurance increased by 3.8% in 2016, compared with a rise of 5.2% in 2015, according to pharmacy benefits manager Express Scripts.

Commercial plans managed by Express Scripts saw the cost of prescription drugs rise by 2.5% per person, while utilization was up by 1.3%, which adds up to the 3.8% overall increase. That represents a 27% drop from 2015, when drug use rose 2.0% and costs went up by 3.2%, Express Scripts said in its “2016 Drug Trend Report.”

[email protected]

AMSTERDAM – Pathological fractures are prognostic of poor outcomes in adults with osteosarcoma, but not in children with osteosarcoma, investigators have found.

A retrospective review of data on consecutive patients treated over the course of 30 years showed that among patients of all ages, both 5-year and 10-year overall survival (OS) rates were worse among patients who had pathological fractures.

But in an analysis stratified by age, the survival difference attributable to fractures was limited entirely to patients who were 18 or older at the time of an osteosarcoma diagnosis, reported Lisa Kelley, a medical student at the Ludwig-Maximilians Universität in Munich.

AMSTERDAM – Pathological fractures are prognostic of poor outcomes in adults with osteosarcoma, but not in children with osteosarcoma, investigators have found.

A retrospective review of data on consecutive patients treated over the course of 30 years showed that among patients of all ages, both 5-year and 10-year overall survival (OS) rates were worse among patients who had pathological fractures.

But in an analysis stratified by age, the survival difference attributable to fractures was limited entirely to patients who were 18 or older at the time of an osteosarcoma diagnosis, reported Lisa Kelley, a medical student at the Ludwig-Maximilians Universität in Munich.

AMSTERDAM – Pathological fractures are prognostic of poor outcomes in adults with osteosarcoma, but not in children with osteosarcoma, investigators have found.

A retrospective review of data on consecutive patients treated over the course of 30 years showed that among patients of all ages, both 5-year and 10-year overall survival (OS) rates were worse among patients who had pathological fractures.

But in an analysis stratified by age, the survival difference attributable to fractures was limited entirely to patients who were 18 or older at the time of an osteosarcoma diagnosis, reported Lisa Kelley, a medical student at the Ludwig-Maximilians Universität in Munich.

From the Maternal and Child Health Research Program, Department of Obstetrics and Gynecology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA (Dr. Hirshberg, Dr. Srinivas); Hospital of the University of Pennsylvania, Department of Nursing, Department of Obstetrics and Gynecology, Philadelphia, PA (Ms. Bittle); Penn Medicine Center for Health Care Innovation, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA (Mr. Vandertuyn, Ms. Mahraj, Dr. Asch, Mr. Rosin); and the Department of Family Medicine, University of Washington, Seattle, WA (Dr. Bennett).

Abstract

• Objective: To investigate engagement with a bidirectional text messaging system as an alternative to in-person follow-up for postpartum women with hypertensive disorders.
• Methods: We utilized rapid-cycle innovation processes to implement postpartum SMS text messaging follow-up in women with hypertensive disorders who delivered between September–December 2014. Patients were given electronic blood pressure cuffs and education before discharge. Standard texts reminded patients to send blood pressures daily on each of the 7 days post discharge. The study obstetrician sent text message responses based on a pre-specified management algorithm. Ability to meet ACOG guidelines was defined as receiving at least 1 reading on post-discharge days 1 or 2 and days 5, 6, or 7.
• Results: We enrolled 32 patients. Six (19%) returned for usual care office blood pressure checks. We received at least 1 blood pressure from 27 (84%) participants. Nearly 20 (65%) texted readings on 5 of the 7 days. 27 (84%) texted at least one reading on day 1 or 2, and 21 (66%) texted at least one pressure on day 5, 6, or 7 (P = 0.001 vs. usual care). Two patients required medications and none were readmitted for hypertension. Patients reported preference for home testing and text messaging over return visits.
• Conclusion: Remote blood pressure monitoring via text messaging is a patient-centered method for postpartum hypertension surveillance. Further testing is needed prior to widespread adoption within the broader obstetric community.

Key words: postpartum hypertension, remote monitoring, text-based intervention.

Hypertensive disease is a leading cause of maternal morbidity and mortality [1,2] and the leading cause of obstetric readmissions, accounting for 27% of obstetric readmissions in the United States in 2009 [3]. The majority of patients readmitted with hypertension have a diagnosis of hypertensive disorder of pregnancy on initial admission for delivery, indicating that these readmissions are the result of disease persistence or progression in contrast to new-onset disease. Peak blood pressure in these patients usually occurs 3 to 6 days postpartum [4–6] and is typically unaccompanied by warning symptoms. For these reasons, identifying patients who are at risk for persistent disease and being proactive in their postpartum care may decrease postpartum stroke and seizure. The recent Hypertension in Pregnancy guidelines provided by the American College of Obstetricians and Gynecologists (ACOG) recommend monitoring blood pressure for at least 72 hours postpartum (inpatient or outpatient) and again 7 to 10 days after delivery in women in whom a hypertensive disease of pregnancy is diagnosed [6].

Although there is a clear need for effective and reliable blood pressure surveillance for high-risk women soon after delivery, significant obstacles exist. Our own high-risk blood pressure transition clinic, which occurred every other week and was staffed by maternal-fetal medicine specialists, had an average attendance of only 30% over a 2-year period. Moreover, all of the hypertension-related readmissions occurred in the first 7 days post discharge, which was before the scheduled clinic visit for approximately 50% of patients. Phone call reminders were also found to be an ineffective strategy, as the women did not answer or return voice messages left by the practice. In fact, a postpartum unit quality improvement project validated that follow-up phone calls after discharge from the postpartum unit were less effective than text messaging when reminding women of their blood pressure follow-up appointment at the clinic [7].

As an alternative to in-person visits or traditional voice telephonic communication, mobile phone “Short Message Service” (SMS) text messaging has been used successfully in health care for appointment reminders, result reporting, support of medication and treatment adherence, and dosage adjustment [8–13]. As of 2014, 90% of American adults own a cell phone and over 79% of those send and receive text messages [14]. Among a young population, which is at high risk for hypertensive disorders of pregnancy, data further reveals a preference for text messaging over live calls [15]. Among low-income women under age 30, the rates of cell phone use and text communication are very high [14,15], making text-based surveillance a promising and more patient-centered strategy for a broad population.

We report the results of rapid-cycle innovation and implementation of active, remote surveillance of hypertension with new text message communication strategies in the first 7 days post-discharge. We chose a Plan-Do-Study-Act cycle approach, in which small tests are performed and studied and changes made to accelerate improvement, in order to enhance our ability to acquire blood pressure data [16,17]. The goals of the work were to (1) assess patient engagement using a remote method of blood pressure monitoring, (2) increase ascertainment of postpartum blood pressure data and obtain at least once daily blood pressure readings on all patients on post discharge days 1–2 and 5–7, which is in accordance with the recommended guidelines [6] for blood pressure surveillance, and (3) address all “at risk” severe range blood pressure readings within a short time interval and prior to the need for readmission. We describe a program of remote blood pressure monitoring and communication via text message designed to increase patient engagement and participation, thereby having the potential to result in earlier interventions, reduce readmissions, and decrease overall morbidity.

Methods

We performed a series of 6 rapid-cycle innovation devel-opment and implementation interventions with a cohort of women with chronic hypertension (CHTN), gestational hypertension (GHTN), or preeclampsia (with and without severe features and superimposed) who delivered at our institution between 20 September 2014 and 14 December 2014. All patients were > 18 years old, able to speak and read English, had a hypertension diag-nosis listed above, and had access to a cell phone with unlimited text messaging capabilities. Patients received standard postpartum care and were continued or started on antihypertensive medications based on a standardized postpartum hypertension protocol previously developed at our institution (available on request). This project was undertaken as a quality improvement initiative and as such was exempt from formal review by our institutional review board. However, all patients signed a waiver acknowledging that SMS texting is not a secure communications technology. A single research telephone was used for physician-patient communication to further ensure privacy.

Patients who qualified for the intervention study were recruited on the postpartum unit following delivery. Those who agreed to participate were provided with electronic blood pressure monitors (CVS Pharmacy automatic blood pressure monitor and Omron 3 Series upper arm blood pressure monitor) prior to discharge and instructed on their use. Patients were told to expect their first text message reminder to send in their blood pressure the day after discharge; an example of a text reminder is “Good morning. Please send us a blood pressure reading by 12 pm.” Patients were enrolled for 7 days post discharge and were interviewed regarding their experience at the end of their 7-day enrollment. As this was primarily a feasibility and quality improvement study, patients were also instructed to continue to follow up with the standard of care at the hypertension clinic visit.

For each of the 7 days following discharge from the hospital, patients received a standard text message in the morning and afternoon reminding them to text their blood pressure to the research telephone by a specific time. Reported blood pressures were reviewed and a standard response was sent by the study obstetrician based on an algorithm consistent with the institution’s postpartum hypertension protocol. Patients were sent reminders at all time points whether or not they had texted any BPs.

The ACOG Hypertension in Pregnancy guidelines recommend monitoring blood pressure at 72 hours postpartum (inpatient or outpatient) and again 7 to 10 days postpartum in women diagnosed with a hypertensive disorder of pregnancy [6]. We measured our ability to meet these guidelines by identifying how many patients texted blood pressures on post-discharge days 1 or 2 and post-discharge days 5, 6, or 7, as most patients were discharged home on postpartum day 2 or 3.

Strategies to enhance patient engagement were modified based on patient interviews and results from the immediately preceding cycle (for example, Cycle 1 interview information and results were used to make changes in Cycle 2), as well as studies on telemonitoring adherence in other populations [18]. The program ended after 6 cycles, as the study team felt there was sufficient promise to design an expanded platform suitable for a larger study.

Results

Overall

At the patient level, we received at least 1 blood pressure during the requested time frame from 27 of the 32 patients enrolled (84%). Nearly 65% of patients (20/32) texted at least 1 blood pressure reading on at least 5 out of the 7 days enrolled. 

By Cycle

Cycle 1 - Basic

Cycle 1 tested our basic hypothesis that patients would take their blood pressure at home and transmit the results by text message: 5 of 7 patients responded to our reminders, each transmitting blood pressures on at least 5 of the 7 days requested.

Four severe-range blood pressures, defined as systolic blood pressure ≥ 160 mm Hg or diastolic blood pressure ≥ 110 [6], were sent to the physician responder, two times each in 2 patients. All four “at risk” severe blood pressures were addressed within 24 hours of the text message. No medications were initiated, as elevated blood pressures were not persistent and patients were asymptomatic.

Cycle 2 - Education

Patients in Cycle 1 reported during their follow-up interview that they became more aware of the possible morbidity associated with persistent postpartum hypertension as the cycle progressed. Therefore, Cycle 2 tested our hypothesis that focused education would improve patient engagement.

All five patients in this cohort sent in at least one blood pressure during the cycle period. All transmitted at least one blood pressure text on post-discharge day 1 or 2. Four of the five patients (80%) also sent in at least one blood pressure on day 5, 6, or 7.

There were no significantly elevated blood pressures sent to the physician responder.

Cycle 3 - Personalization

Patients in Cycle 2 reported during their interview that they felt the text message responses from the provider were too automated. Cycle 3 tested our hypothesis that added personalization, with patient and infant names included in the messages, would improve engagement.

Three of five patients in this cohort sent at least one blood pressure text on post-discharge day 1 or 2 (60%). Only one patient (20%) also sent in at least one blood pressure on day 5, 6, or 7.

One significantly elevated blood pressure was sent to the physician responder. This blood pressure was addressed within 24 hours of the text message. No medications were initiated, as elevated blood pressures were not persistent and patients were asymptomatic.

Cycle 4 - Response Timing

Patients in Cycle 3 had lower response rates than previous cycles and noted that they wanted more flexibility in the time to respond, as their schedules were unpredictable with a newborn at home. Although they enjoyed the personalized aspect, they did not feel it influenced their responses, which is evidenced by the low response rate on days 5, 6, or 7. Therefore, Cycle 4 tested our hypothesis that allowing patients to commit to a time of their choice for receiving the reminder texts would improve their response rate.

All five patients enrolled in this cohort sent in at least one blood pressure. We received at least one blood pressure text on post-discharge day 1 or 2 from all five patients in this cycle (100%). Three of the five patients (60%) also sent in at least one blood pressure on day 5, 6, or 7.

Five severely elevated blood pressures were sent to the physician responder, all from a single patient. This patient had been discharged home on hydrochlorothiazide 12.5 mg for persistently elevated blood pressures while in the hospital after being diagnosed with severe preeclampsia. All five “at risk” blood pressures were addressed within 24 hours of the text message. On her fifth day of remote surveillance, 5 mg of amlodipine was added to her daily regimen for blood pressures ranging from 150–170/90–110 mm Hg. Her blood pressure at her 6-week postpartum visit was 120/60 mm Hg and she had seen her primary care doctor in the interim for further hypertension management.

Cycle 5 - Snooze and Countdown

Although most of the patients enrolled in Cycle 4 stated that they were very busy in the immediate postpartum period and not always able to respond in a timely fashion, allowing patients to receive the reminder text at their own designated convenient time did not increase engagement. Patients reported that while they always carried their cell phones, they did not always carry their blood pressure cuff, limiting their ability to send in a reading at the time of the reminder. Additionally, patients reported feeling less motivated to continue texting blood pressures towards the end of the cycle. Cycle 5 tested our hypothesis that patient engagement would improve if reminder text messages were sent closer to the morning or evening deadline. Patients were provided with the opportunity to request “snooze” response if they did have their cuff accessible. Additionally, standard responses were accompanied by a countdown message. For example, “Your blood pressure looks good. Four more days of checking your blood pressure to go.”

All five enrolled in this cohort sent in at least one blood pressure, and all (100%) transmitted at least one blood pressure text on post-discharge day 1 or 2 and on day 5, 6, or 7. Only two “snooze” requests were made over the course of the arm by a single patient, who responded both times after the additional reminder.

Four severely elevated blood pressures were sent to the physician responder, all from a single patient. This patient was diagnosed with preeclampsia with severe features on delivery admission, and her blood pressures normalized prior to discharge. All four “at risk” blood pressures were addressed within 24 hours of the text message. Due to persistently elevated diastolic blood pressures ranging from 110–120 mm Hg, she was started on hydrochlorothiazide 12.5 mg on day 6 of the cycle and monitored for additional days following cycle completion with improved blood pressures.

Cycle 6 - Snooze and Support Person

The patients in Cycle 5 were overall satisfied with their experience and did not provide any suggestions for change. However, we sought to see if integrating support persons into the protocol would affect engagement. Cycle 6 tested our hypothesis that patients would be more engaged if they had a self-identified support person reminding them to text their blood pressures. Patients provided the name of a support person to contact if a morning blood pressure was not received. Additionally, patients received the same “snooze” option as in Cycle 5. A total of five patients were enrolled in this cohort; one patient enrolled in the trial but did not send in any blood pressures despite daily reminders to both her and her support buddy. Only 2 additional buddy notifications were required in patients who did not send in a morning blood pressure reading and both times a subsequent blood pressure was sent. Two “snooze” requests were made over the course of the cycle by a single patient, who responded both times after the reminder.

Four of five patients in this cohort sent at least one blood pressure text on post-discharge day 1 or 2 (80%). Three patients (60%) also sent in at least one blood pressure on day 5, 6, or 7.

There were no significantly elevated blood pressures sent to the physician responder and no medications were initiated.

Post-Cycle Interviews

Overall, patients reported satisfaction with the text messaging system in their post-cycle interviews. The convenience of the intervention was acknowledged by many, including one patient who commented that “this was a lot better than having to pay for the bus and waiting for hours in some waiting room.” One patient also reported that the increased awareness was important, stating that “when [she] got home and realized that [her blood pressure] was still high, [she] did her own research and learned more about hypertension and preeclampsia.” Others reported that they still checked their blood pressure after the cycle, and “would have went longer than a week if they had asked me to.”

Discussions

Our results suggest that remote blood pressure monitoring via text message communication engages patients and shows promise as a convenient and effective means of hypertension surveillance in the immediate postpartum period, in accordance to ACOG guidelines. Additionally, we were able to test this monitoring system using inexpensive, rapid-cycle validation techniques. Although these techniques are insufficiently controlled and of inadequate statistical power for definitive results, they were able to provide quick evidence toward a pragmatic and workable solution to an important clinical problem within the specific clinical context of our practice, though the results are likely to generalize to other settings. We found varied compliance based on the different engagement strategies, and although no single cycle proved superior, overall patient participation was good and provides a basis for different texting options in future work. Developing a method that both engages patients and is streamlined for providers is critical to our ability to translate this recommendation into practice. Although we did not specifically test how the system works from a provider’s point of view, the study obstetricians believe that this would help and can be fit within the existing workflows of the practices at most institutions.

This rapid-cycle intervention study provides several additional lessons, as we were able to rapidly implement this on our unit and test several hypotheses related to patient engagement. Most patients found the text messaging system to be a convenient way to communicate with their obstetrician. Even when patients had prenatal care at other institutions and delivered at our hospital without a prior patient/physician relationship (n = 5), we were able to engage them in text messaging. However, there was some evidence of patient drop out over the course of the week, as patients were more likely to text in blood pressure in the first few days of the cycle than the last few days (Figure 2).

Other telemedicine interventions have been studied in maternity care and have had inconsistent results. The Cochrane review on telephone support for women during pregnancy and up to 6 weeks after birth found that interventions were mainly aimed at smoking cessation, breastfeeding continuation, preterm birth, and postpartum depression [19]. To date, none of the randomized trials in pregnancy or the postpartum period have focused on postpartum hypertension. The results of our interventions are encouraging and support the use of text messaging in obstetrical care, particularly in the postpartum period. While text messaging cannot provide all the information that can be obtained in a doctor’s visit, such as physical exam, urine dipsticks, and review of symptoms, it can identify the minority of patients that may need to be seen in the office based on the severity of their blood pressures.

While some cases of postpartum preeclampsia occur in the absence of peripartum disease, most readmitted patients are diagnosed with preeclampsia prior to delivery and readmission is due to worsening or persistence of disease and therefore, potentially preventable. These patients are the primary target of our intervention, as remote hypertension surveillance provides an opportunity to start or adjust medications and minimize both patient inconvenience and hospital cost of a readmission.

However, our feasibility study has some limitations. Despite overall patient satisfaction, acceptability, and compliance with text message monitoring of hypertension, the small sample size and qualitative nature of our cycles merits further pursuit and follow-up studies prior to implementation. Overall, we had only a small number of elevated blood pressures requiring intervention; however, this underscores the need to identify patients most at risk for persistent or delayed hypertension and the importance of developing a method of follow-up that engages all patients. Additionally, as patients were asked to both text in blood pressure values and also present for office visits, and therefore acted as their own control, it is not surprising that more patients were compliant with the simple texting method than standard of care; however, even when comparing texting compliance to historical attendance in our clinic of only 30%, our results remain promising.

While our results are encouraging, we believe it is important to test text messaging surveillance and patient compliance in a larger trial prior to implementing within the broader community. This study provides critical data to support the development of a HIPAA-compliant, automated monitoring system that can provide timely responses to patient texts using a provider derived response to blood pressure values. Future work includes the development of an automated hypertension tool as well as a randomized controlled trial to more rigorously compare office blood pressure visits to remote text message surveillance. If effective, use of text messaging technology may allow for an improved patient partnership and more robust follow-up data, especially in patients with less than optimal compliance, as well as the ability to improve maternal care and decrease morbidity and mortality.

Corresponding author: Adi Hirshberg, MD, Dept. of Maternal-Fetal Medicine, 2 Silverstein, 3400 Spruce St., Philadelphia, PA 19104, [email protected].

Funding/support: Supported by a Penn Medicine Innovation Accelerator grant.

Financial disclosures. None reported.

From the Maternal and Child Health Research Program, Department of Obstetrics and Gynecology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA (Dr. Hirshberg, Dr. Srinivas); Hospital of the University of Pennsylvania, Department of Nursing, Department of Obstetrics and Gynecology, Philadelphia, PA (Ms. Bittle); Penn Medicine Center for Health Care Innovation, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA (Mr. Vandertuyn, Ms. Mahraj, Dr. Asch, Mr. Rosin); and the Department of Family Medicine, University of Washington, Seattle, WA (Dr. Bennett).

Abstract

• Objective: To investigate engagement with a bidirectional text messaging system as an alternative to in-person follow-up for postpartum women with hypertensive disorders.
• Methods: We utilized rapid-cycle innovation processes to implement postpartum SMS text messaging follow-up in women with hypertensive disorders who delivered between September–December 2014. Patients were given electronic blood pressure cuffs and education before discharge. Standard texts reminded patients to send blood pressures daily on each of the 7 days post discharge. The study obstetrician sent text message responses based on a pre-specified management algorithm. Ability to meet ACOG guidelines was defined as receiving at least 1 reading on post-discharge days 1 or 2 and days 5, 6, or 7.
• Results: We enrolled 32 patients. Six (19%) returned for usual care office blood pressure checks. We received at least 1 blood pressure from 27 (84%) participants. Nearly 20 (65%) texted readings on 5 of the 7 days. 27 (84%) texted at least one reading on day 1 or 2, and 21 (66%) texted at least one pressure on day 5, 6, or 7 (P = 0.001 vs. usual care). Two patients required medications and none were readmitted for hypertension. Patients reported preference for home testing and text messaging over return visits.
• Conclusion: Remote blood pressure monitoring via text messaging is a patient-centered method for postpartum hypertension surveillance. Further testing is needed prior to widespread adoption within the broader obstetric community.

Key words: postpartum hypertension, remote monitoring, text-based intervention.

Hypertensive disease is a leading cause of maternal morbidity and mortality [1,2] and the leading cause of obstetric readmissions, accounting for 27% of obstetric readmissions in the United States in 2009 [3]. The majority of patients readmitted with hypertension have a diagnosis of hypertensive disorder of pregnancy on initial admission for delivery, indicating that these readmissions are the result of disease persistence or progression in contrast to new-onset disease. Peak blood pressure in these patients usually occurs 3 to 6 days postpartum [4–6] and is typically unaccompanied by warning symptoms. For these reasons, identifying patients who are at risk for persistent disease and being proactive in their postpartum care may decrease postpartum stroke and seizure. The recent Hypertension in Pregnancy guidelines provided by the American College of Obstetricians and Gynecologists (ACOG) recommend monitoring blood pressure for at least 72 hours postpartum (inpatient or outpatient) and again 7 to 10 days after delivery in women in whom a hypertensive disease of pregnancy is diagnosed [6].

Although there is a clear need for effective and reliable blood pressure surveillance for high-risk women soon after delivery, significant obstacles exist. Our own high-risk blood pressure transition clinic, which occurred every other week and was staffed by maternal-fetal medicine specialists, had an average attendance of only 30% over a 2-year period. Moreover, all of the hypertension-related readmissions occurred in the first 7 days post discharge, which was before the scheduled clinic visit for approximately 50% of patients. Phone call reminders were also found to be an ineffective strategy, as the women did not answer or return voice messages left by the practice. In fact, a postpartum unit quality improvement project validated that follow-up phone calls after discharge from the postpartum unit were less effective than text messaging when reminding women of their blood pressure follow-up appointment at the clinic [7].

As an alternative to in-person visits or traditional voice telephonic communication, mobile phone “Short Message Service” (SMS) text messaging has been used successfully in health care for appointment reminders, result reporting, support of medication and treatment adherence, and dosage adjustment [8–13]. As of 2014, 90% of American adults own a cell phone and over 79% of those send and receive text messages [14]. Among a young population, which is at high risk for hypertensive disorders of pregnancy, data further reveals a preference for text messaging over live calls [15]. Among low-income women under age 30, the rates of cell phone use and text communication are very high [14,15], making text-based surveillance a promising and more patient-centered strategy for a broad population.

We report the results of rapid-cycle innovation and implementation of active, remote surveillance of hypertension with new text message communication strategies in the first 7 days post-discharge. We chose a Plan-Do-Study-Act cycle approach, in which small tests are performed and studied and changes made to accelerate improvement, in order to enhance our ability to acquire blood pressure data [16,17]. The goals of the work were to (1) assess patient engagement using a remote method of blood pressure monitoring, (2) increase ascertainment of postpartum blood pressure data and obtain at least once daily blood pressure readings on all patients on post discharge days 1–2 and 5–7, which is in accordance with the recommended guidelines [6] for blood pressure surveillance, and (3) address all “at risk” severe range blood pressure readings within a short time interval and prior to the need for readmission. We describe a program of remote blood pressure monitoring and communication via text message designed to increase patient engagement and participation, thereby having the potential to result in earlier interventions, reduce readmissions, and decrease overall morbidity.

Methods

We performed a series of 6 rapid-cycle innovation devel-opment and implementation interventions with a cohort of women with chronic hypertension (CHTN), gestational hypertension (GHTN), or preeclampsia (with and without severe features and superimposed) who delivered at our institution between 20 September 2014 and 14 December 2014. All patients were > 18 years old, able to speak and read English, had a hypertension diag-nosis listed above, and had access to a cell phone with unlimited text messaging capabilities. Patients received standard postpartum care and were continued or started on antihypertensive medications based on a standardized postpartum hypertension protocol previously developed at our institution (available on request). This project was undertaken as a quality improvement initiative and as such was exempt from formal review by our institutional review board. However, all patients signed a waiver acknowledging that SMS texting is not a secure communications technology. A single research telephone was used for physician-patient communication to further ensure privacy.

Patients who qualified for the intervention study were recruited on the postpartum unit following delivery. Those who agreed to participate were provided with electronic blood pressure monitors (CVS Pharmacy automatic blood pressure monitor and Omron 3 Series upper arm blood pressure monitor) prior to discharge and instructed on their use. Patients were told to expect their first text message reminder to send in their blood pressure the day after discharge; an example of a text reminder is “Good morning. Please send us a blood pressure reading by 12 pm.” Patients were enrolled for 7 days post discharge and were interviewed regarding their experience at the end of their 7-day enrollment. As this was primarily a feasibility and quality improvement study, patients were also instructed to continue to follow up with the standard of care at the hypertension clinic visit.

For each of the 7 days following discharge from the hospital, patients received a standard text message in the morning and afternoon reminding them to text their blood pressure to the research telephone by a specific time. Reported blood pressures were reviewed and a standard response was sent by the study obstetrician based on an algorithm consistent with the institution’s postpartum hypertension protocol. Patients were sent reminders at all time points whether or not they had texted any BPs.

The ACOG Hypertension in Pregnancy guidelines recommend monitoring blood pressure at 72 hours postpartum (inpatient or outpatient) and again 7 to 10 days postpartum in women diagnosed with a hypertensive disorder of pregnancy [6]. We measured our ability to meet these guidelines by identifying how many patients texted blood pressures on post-discharge days 1 or 2 and post-discharge days 5, 6, or 7, as most patients were discharged home on postpartum day 2 or 3.

Strategies to enhance patient engagement were modified based on patient interviews and results from the immediately preceding cycle (for example, Cycle 1 interview information and results were used to make changes in Cycle 2), as well as studies on telemonitoring adherence in other populations [18]. The program ended after 6 cycles, as the study team felt there was sufficient promise to design an expanded platform suitable for a larger study.

Results

Overall

At the patient level, we received at least 1 blood pressure during the requested time frame from 27 of the 32 patients enrolled (84%). Nearly 65% of patients (20/32) texted at least 1 blood pressure reading on at least 5 out of the 7 days enrolled. 

By Cycle

Cycle 1 - Basic

Cycle 1 tested our basic hypothesis that patients would take their blood pressure at home and transmit the results by text message: 5 of 7 patients responded to our reminders, each transmitting blood pressures on at least 5 of the 7 days requested.

Four severe-range blood pressures, defined as systolic blood pressure ≥ 160 mm Hg or diastolic blood pressure ≥ 110 [6], were sent to the physician responder, two times each in 2 patients. All four “at risk” severe blood pressures were addressed within 24 hours of the text message. No medications were initiated, as elevated blood pressures were not persistent and patients were asymptomatic.

Cycle 2 - Education

Patients in Cycle 1 reported during their follow-up interview that they became more aware of the possible morbidity associated with persistent postpartum hypertension as the cycle progressed. Therefore, Cycle 2 tested our hypothesis that focused education would improve patient engagement.

All five patients in this cohort sent in at least one blood pressure during the cycle period. All transmitted at least one blood pressure text on post-discharge day 1 or 2. Four of the five patients (80%) also sent in at least one blood pressure on day 5, 6, or 7.

There were no significantly elevated blood pressures sent to the physician responder.

Cycle 3 - Personalization

Patients in Cycle 2 reported during their interview that they felt the text message responses from the provider were too automated. Cycle 3 tested our hypothesis that added personalization, with patient and infant names included in the messages, would improve engagement.

Three of five patients in this cohort sent at least one blood pressure text on post-discharge day 1 or 2 (60%). Only one patient (20%) also sent in at least one blood pressure on day 5, 6, or 7.

One significantly elevated blood pressure was sent to the physician responder. This blood pressure was addressed within 24 hours of the text message. No medications were initiated, as elevated blood pressures were not persistent and patients were asymptomatic.

Cycle 4 - Response Timing

Patients in Cycle 3 had lower response rates than previous cycles and noted that they wanted more flexibility in the time to respond, as their schedules were unpredictable with a newborn at home. Although they enjoyed the personalized aspect, they did not feel it influenced their responses, which is evidenced by the low response rate on days 5, 6, or 7. Therefore, Cycle 4 tested our hypothesis that allowing patients to commit to a time of their choice for receiving the reminder texts would improve their response rate.

All five patients enrolled in this cohort sent in at least one blood pressure. We received at least one blood pressure text on post-discharge day 1 or 2 from all five patients in this cycle (100%). Three of the five patients (60%) also sent in at least one blood pressure on day 5, 6, or 7.

Five severely elevated blood pressures were sent to the physician responder, all from a single patient. This patient had been discharged home on hydrochlorothiazide 12.5 mg for persistently elevated blood pressures while in the hospital after being diagnosed with severe preeclampsia. All five “at risk” blood pressures were addressed within 24 hours of the text message. On her fifth day of remote surveillance, 5 mg of amlodipine was added to her daily regimen for blood pressures ranging from 150–170/90–110 mm Hg. Her blood pressure at her 6-week postpartum visit was 120/60 mm Hg and she had seen her primary care doctor in the interim for further hypertension management.

Cycle 5 - Snooze and Countdown

Although most of the patients enrolled in Cycle 4 stated that they were very busy in the immediate postpartum period and not always able to respond in a timely fashion, allowing patients to receive the reminder text at their own designated convenient time did not increase engagement. Patients reported that while they always carried their cell phones, they did not always carry their blood pressure cuff, limiting their ability to send in a reading at the time of the reminder. Additionally, patients reported feeling less motivated to continue texting blood pressures towards the end of the cycle. Cycle 5 tested our hypothesis that patient engagement would improve if reminder text messages were sent closer to the morning or evening deadline. Patients were provided with the opportunity to request “snooze” response if they did have their cuff accessible. Additionally, standard responses were accompanied by a countdown message. For example, “Your blood pressure looks good. Four more days of checking your blood pressure to go.”

All five enrolled in this cohort sent in at least one blood pressure, and all (100%) transmitted at least one blood pressure text on post-discharge day 1 or 2 and on day 5, 6, or 7. Only two “snooze” requests were made over the course of the arm by a single patient, who responded both times after the additional reminder.

Four severely elevated blood pressures were sent to the physician responder, all from a single patient. This patient was diagnosed with preeclampsia with severe features on delivery admission, and her blood pressures normalized prior to discharge. All four “at risk” blood pressures were addressed within 24 hours of the text message. Due to persistently elevated diastolic blood pressures ranging from 110–120 mm Hg, she was started on hydrochlorothiazide 12.5 mg on day 6 of the cycle and monitored for additional days following cycle completion with improved blood pressures.

Cycle 6 - Snooze and Support Person

The patients in Cycle 5 were overall satisfied with their experience and did not provide any suggestions for change. However, we sought to see if integrating support persons into the protocol would affect engagement. Cycle 6 tested our hypothesis that patients would be more engaged if they had a self-identified support person reminding them to text their blood pressures. Patients provided the name of a support person to contact if a morning blood pressure was not received. Additionally, patients received the same “snooze” option as in Cycle 5. A total of five patients were enrolled in this cohort; one patient enrolled in the trial but did not send in any blood pressures despite daily reminders to both her and her support buddy. Only 2 additional buddy notifications were required in patients who did not send in a morning blood pressure reading and both times a subsequent blood pressure was sent. Two “snooze” requests were made over the course of the cycle by a single patient, who responded both times after the reminder.

Four of five patients in this cohort sent at least one blood pressure text on post-discharge day 1 or 2 (80%). Three patients (60%) also sent in at least one blood pressure on day 5, 6, or 7.

There were no significantly elevated blood pressures sent to the physician responder and no medications were initiated.

Post-Cycle Interviews

Overall, patients reported satisfaction with the text messaging system in their post-cycle interviews. The convenience of the intervention was acknowledged by many, including one patient who commented that “this was a lot better than having to pay for the bus and waiting for hours in some waiting room.” One patient also reported that the increased awareness was important, stating that “when [she] got home and realized that [her blood pressure] was still high, [she] did her own research and learned more about hypertension and preeclampsia.” Others reported that they still checked their blood pressure after the cycle, and “would have went longer than a week if they had asked me to.”

Discussions

Our results suggest that remote blood pressure monitoring via text message communication engages patients and shows promise as a convenient and effective means of hypertension surveillance in the immediate postpartum period, in accordance to ACOG guidelines. Additionally, we were able to test this monitoring system using inexpensive, rapid-cycle validation techniques. Although these techniques are insufficiently controlled and of inadequate statistical power for definitive results, they were able to provide quick evidence toward a pragmatic and workable solution to an important clinical problem within the specific clinical context of our practice, though the results are likely to generalize to other settings. We found varied compliance based on the different engagement strategies, and although no single cycle proved superior, overall patient participation was good and provides a basis for different texting options in future work. Developing a method that both engages patients and is streamlined for providers is critical to our ability to translate this recommendation into practice. Although we did not specifically test how the system works from a provider’s point of view, the study obstetricians believe that this would help and can be fit within the existing workflows of the practices at most institutions.

This rapid-cycle intervention study provides several additional lessons, as we were able to rapidly implement this on our unit and test several hypotheses related to patient engagement. Most patients found the text messaging system to be a convenient way to communicate with their obstetrician. Even when patients had prenatal care at other institutions and delivered at our hospital without a prior patient/physician relationship (n = 5), we were able to engage them in text messaging. However, there was some evidence of patient drop out over the course of the week, as patients were more likely to text in blood pressure in the first few days of the cycle than the last few days (Figure 2).

Other telemedicine interventions have been studied in maternity care and have had inconsistent results. The Cochrane review on telephone support for women during pregnancy and up to 6 weeks after birth found that interventions were mainly aimed at smoking cessation, breastfeeding continuation, preterm birth, and postpartum depression [19]. To date, none of the randomized trials in pregnancy or the postpartum period have focused on postpartum hypertension. The results of our interventions are encouraging and support the use of text messaging in obstetrical care, particularly in the postpartum period. While text messaging cannot provide all the information that can be obtained in a doctor’s visit, such as physical exam, urine dipsticks, and review of symptoms, it can identify the minority of patients that may need to be seen in the office based on the severity of their blood pressures.

While some cases of postpartum preeclampsia occur in the absence of peripartum disease, most readmitted patients are diagnosed with preeclampsia prior to delivery and readmission is due to worsening or persistence of disease and therefore, potentially preventable. These patients are the primary target of our intervention, as remote hypertension surveillance provides an opportunity to start or adjust medications and minimize both patient inconvenience and hospital cost of a readmission.

However, our feasibility study has some limitations. Despite overall patient satisfaction, acceptability, and compliance with text message monitoring of hypertension, the small sample size and qualitative nature of our cycles merits further pursuit and follow-up studies prior to implementation. Overall, we had only a small number of elevated blood pressures requiring intervention; however, this underscores the need to identify patients most at risk for persistent or delayed hypertension and the importance of developing a method of follow-up that engages all patients. Additionally, as patients were asked to both text in blood pressure values and also present for office visits, and therefore acted as their own control, it is not surprising that more patients were compliant with the simple texting method than standard of care; however, even when comparing texting compliance to historical attendance in our clinic of only 30%, our results remain promising.

While our results are encouraging, we believe it is important to test text messaging surveillance and patient compliance in a larger trial prior to implementing within the broader community. This study provides critical data to support the development of a HIPAA-compliant, automated monitoring system that can provide timely responses to patient texts using a provider derived response to blood pressure values. Future work includes the development of an automated hypertension tool as well as a randomized controlled trial to more rigorously compare office blood pressure visits to remote text message surveillance. If effective, use of text messaging technology may allow for an improved patient partnership and more robust follow-up data, especially in patients with less than optimal compliance, as well as the ability to improve maternal care and decrease morbidity and mortality.

Corresponding author: Adi Hirshberg, MD, Dept. of Maternal-Fetal Medicine, 2 Silverstein, 3400 Spruce St., Philadelphia, PA 19104, [email protected].

Funding/support: Supported by a Penn Medicine Innovation Accelerator grant.

Financial disclosures. None reported.

From the Maternal and Child Health Research Program, Department of Obstetrics and Gynecology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA (Dr. Hirshberg, Dr. Srinivas); Hospital of the University of Pennsylvania, Department of Nursing, Department of Obstetrics and Gynecology, Philadelphia, PA (Ms. Bittle); Penn Medicine Center for Health Care Innovation, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA (Mr. Vandertuyn, Ms. Mahraj, Dr. Asch, Mr. Rosin); and the Department of Family Medicine, University of Washington, Seattle, WA (Dr. Bennett).

Abstract

• Objective: To investigate engagement with a bidirectional text messaging system as an alternative to in-person follow-up for postpartum women with hypertensive disorders.
• Methods: We utilized rapid-cycle innovation processes to implement postpartum SMS text messaging follow-up in women with hypertensive disorders who delivered between September–December 2014. Patients were given electronic blood pressure cuffs and education before discharge. Standard texts reminded patients to send blood pressures daily on each of the 7 days post discharge. The study obstetrician sent text message responses based on a pre-specified management algorithm. Ability to meet ACOG guidelines was defined as receiving at least 1 reading on post-discharge days 1 or 2 and days 5, 6, or 7.
• Results: We enrolled 32 patients. Six (19%) returned for usual care office blood pressure checks. We received at least 1 blood pressure from 27 (84%) participants. Nearly 20 (65%) texted readings on 5 of the 7 days. 27 (84%) texted at least one reading on day 1 or 2, and 21 (66%) texted at least one pressure on day 5, 6, or 7 (P = 0.001 vs. usual care). Two patients required medications and none were readmitted for hypertension. Patients reported preference for home testing and text messaging over return visits.
• Conclusion: Remote blood pressure monitoring via text messaging is a patient-centered method for postpartum hypertension surveillance. Further testing is needed prior to widespread adoption within the broader obstetric community.

Key words: postpartum hypertension, remote monitoring, text-based intervention.

Hypertensive disease is a leading cause of maternal morbidity and mortality [1,2] and the leading cause of obstetric readmissions, accounting for 27% of obstetric readmissions in the United States in 2009 [3]. The majority of patients readmitted with hypertension have a diagnosis of hypertensive disorder of pregnancy on initial admission for delivery, indicating that these readmissions are the result of disease persistence or progression in contrast to new-onset disease. Peak blood pressure in these patients usually occurs 3 to 6 days postpartum [4–6] and is typically unaccompanied by warning symptoms. For these reasons, identifying patients who are at risk for persistent disease and being proactive in their postpartum care may decrease postpartum stroke and seizure. The recent Hypertension in Pregnancy guidelines provided by the American College of Obstetricians and Gynecologists (ACOG) recommend monitoring blood pressure for at least 72 hours postpartum (inpatient or outpatient) and again 7 to 10 days after delivery in women in whom a hypertensive disease of pregnancy is diagnosed [6].

Although there is a clear need for effective and reliable blood pressure surveillance for high-risk women soon after delivery, significant obstacles exist. Our own high-risk blood pressure transition clinic, which occurred every other week and was staffed by maternal-fetal medicine specialists, had an average attendance of only 30% over a 2-year period. Moreover, all of the hypertension-related readmissions occurred in the first 7 days post discharge, which was before the scheduled clinic visit for approximately 50% of patients. Phone call reminders were also found to be an ineffective strategy, as the women did not answer or return voice messages left by the practice. In fact, a postpartum unit quality improvement project validated that follow-up phone calls after discharge from the postpartum unit were less effective than text messaging when reminding women of their blood pressure follow-up appointment at the clinic [7].

As an alternative to in-person visits or traditional voice telephonic communication, mobile phone “Short Message Service” (SMS) text messaging has been used successfully in health care for appointment reminders, result reporting, support of medication and treatment adherence, and dosage adjustment [8–13]. As of 2014, 90% of American adults own a cell phone and over 79% of those send and receive text messages [14]. Among a young population, which is at high risk for hypertensive disorders of pregnancy, data further reveals a preference for text messaging over live calls [15]. Among low-income women under age 30, the rates of cell phone use and text communication are very high [14,15], making text-based surveillance a promising and more patient-centered strategy for a broad population.

We report the results of rapid-cycle innovation and implementation of active, remote surveillance of hypertension with new text message communication strategies in the first 7 days post-discharge. We chose a Plan-Do-Study-Act cycle approach, in which small tests are performed and studied and changes made to accelerate improvement, in order to enhance our ability to acquire blood pressure data [16,17]. The goals of the work were to (1) assess patient engagement using a remote method of blood pressure monitoring, (2) increase ascertainment of postpartum blood pressure data and obtain at least once daily blood pressure readings on all patients on post discharge days 1–2 and 5–7, which is in accordance with the recommended guidelines [6] for blood pressure surveillance, and (3) address all “at risk” severe range blood pressure readings within a short time interval and prior to the need for readmission. We describe a program of remote blood pressure monitoring and communication via text message designed to increase patient engagement and participation, thereby having the potential to result in earlier interventions, reduce readmissions, and decrease overall morbidity.

Methods

We performed a series of 6 rapid-cycle innovation devel-opment and implementation interventions with a cohort of women with chronic hypertension (CHTN), gestational hypertension (GHTN), or preeclampsia (with and without severe features and superimposed) who delivered at our institution between 20 September 2014 and 14 December 2014. All patients were > 18 years old, able to speak and read English, had a hypertension diag-nosis listed above, and had access to a cell phone with unlimited text messaging capabilities. Patients received standard postpartum care and were continued or started on antihypertensive medications based on a standardized postpartum hypertension protocol previously developed at our institution (available on request). This project was undertaken as a quality improvement initiative and as such was exempt from formal review by our institutional review board. However, all patients signed a waiver acknowledging that SMS texting is not a secure communications technology. A single research telephone was used for physician-patient communication to further ensure privacy.

Patients who qualified for the intervention study were recruited on the postpartum unit following delivery. Those who agreed to participate were provided with electronic blood pressure monitors (CVS Pharmacy automatic blood pressure monitor and Omron 3 Series upper arm blood pressure monitor) prior to discharge and instructed on their use. Patients were told to expect their first text message reminder to send in their blood pressure the day after discharge; an example of a text reminder is “Good morning. Please send us a blood pressure reading by 12 pm.” Patients were enrolled for 7 days post discharge and were interviewed regarding their experience at the end of their 7-day enrollment. As this was primarily a feasibility and quality improvement study, patients were also instructed to continue to follow up with the standard of care at the hypertension clinic visit.

For each of the 7 days following discharge from the hospital, patients received a standard text message in the morning and afternoon reminding them to text their blood pressure to the research telephone by a specific time. Reported blood pressures were reviewed and a standard response was sent by the study obstetrician based on an algorithm consistent with the institution’s postpartum hypertension protocol. Patients were sent reminders at all time points whether or not they had texted any BPs.

The ACOG Hypertension in Pregnancy guidelines recommend monitoring blood pressure at 72 hours postpartum (inpatient or outpatient) and again 7 to 10 days postpartum in women diagnosed with a hypertensive disorder of pregnancy [6]. We measured our ability to meet these guidelines by identifying how many patients texted blood pressures on post-discharge days 1 or 2 and post-discharge days 5, 6, or 7, as most patients were discharged home on postpartum day 2 or 3.

Strategies to enhance patient engagement were modified based on patient interviews and results from the immediately preceding cycle (for example, Cycle 1 interview information and results were used to make changes in Cycle 2), as well as studies on telemonitoring adherence in other populations [18]. The program ended after 6 cycles, as the study team felt there was sufficient promise to design an expanded platform suitable for a larger study.

Results

Overall

At the patient level, we received at least 1 blood pressure during the requested time frame from 27 of the 32 patients enrolled (84%). Nearly 65% of patients (20/32) texted at least 1 blood pressure reading on at least 5 out of the 7 days enrolled. 

By Cycle

Cycle 1 - Basic

Cycle 1 tested our basic hypothesis that patients would take their blood pressure at home and transmit the results by text message: 5 of 7 patients responded to our reminders, each transmitting blood pressures on at least 5 of the 7 days requested.

Four severe-range blood pressures, defined as systolic blood pressure ≥ 160 mm Hg or diastolic blood pressure ≥ 110 [6], were sent to the physician responder, two times each in 2 patients. All four “at risk” severe blood pressures were addressed within 24 hours of the text message. No medications were initiated, as elevated blood pressures were not persistent and patients were asymptomatic.

Cycle 2 - Education

Patients in Cycle 1 reported during their follow-up interview that they became more aware of the possible morbidity associated with persistent postpartum hypertension as the cycle progressed. Therefore, Cycle 2 tested our hypothesis that focused education would improve patient engagement.

All five patients in this cohort sent in at least one blood pressure during the cycle period. All transmitted at least one blood pressure text on post-discharge day 1 or 2. Four of the five patients (80%) also sent in at least one blood pressure on day 5, 6, or 7.

There were no significantly elevated blood pressures sent to the physician responder.

Cycle 3 - Personalization

Patients in Cycle 2 reported during their interview that they felt the text message responses from the provider were too automated. Cycle 3 tested our hypothesis that added personalization, with patient and infant names included in the messages, would improve engagement.

Three of five patients in this cohort sent at least one blood pressure text on post-discharge day 1 or 2 (60%). Only one patient (20%) also sent in at least one blood pressure on day 5, 6, or 7.

One significantly elevated blood pressure was sent to the physician responder. This blood pressure was addressed within 24 hours of the text message. No medications were initiated, as elevated blood pressures were not persistent and patients were asymptomatic.

Cycle 4 - Response Timing

Patients in Cycle 3 had lower response rates than previous cycles and noted that they wanted more flexibility in the time to respond, as their schedules were unpredictable with a newborn at home. Although they enjoyed the personalized aspect, they did not feel it influenced their responses, which is evidenced by the low response rate on days 5, 6, or 7. Therefore, Cycle 4 tested our hypothesis that allowing patients to commit to a time of their choice for receiving the reminder texts would improve their response rate.

All five patients enrolled in this cohort sent in at least one blood pressure. We received at least one blood pressure text on post-discharge day 1 or 2 from all five patients in this cycle (100%). Three of the five patients (60%) also sent in at least one blood pressure on day 5, 6, or 7.

Five severely elevated blood pressures were sent to the physician responder, all from a single patient. This patient had been discharged home on hydrochlorothiazide 12.5 mg for persistently elevated blood pressures while in the hospital after being diagnosed with severe preeclampsia. All five “at risk” blood pressures were addressed within 24 hours of the text message. On her fifth day of remote surveillance, 5 mg of amlodipine was added to her daily regimen for blood pressures ranging from 150–170/90–110 mm Hg. Her blood pressure at her 6-week postpartum visit was 120/60 mm Hg and she had seen her primary care doctor in the interim for further hypertension management.

Cycle 5 - Snooze and Countdown

Although most of the patients enrolled in Cycle 4 stated that they were very busy in the immediate postpartum period and not always able to respond in a timely fashion, allowing patients to receive the reminder text at their own designated convenient time did not increase engagement. Patients reported that while they always carried their cell phones, they did not always carry their blood pressure cuff, limiting their ability to send in a reading at the time of the reminder. Additionally, patients reported feeling less motivated to continue texting blood pressures towards the end of the cycle. Cycle 5 tested our hypothesis that patient engagement would improve if reminder text messages were sent closer to the morning or evening deadline. Patients were provided with the opportunity to request “snooze” response if they did have their cuff accessible. Additionally, standard responses were accompanied by a countdown message. For example, “Your blood pressure looks good. Four more days of checking your blood pressure to go.”

All five enrolled in this cohort sent in at least one blood pressure, and all (100%) transmitted at least one blood pressure text on post-discharge day 1 or 2 and on day 5, 6, or 7. Only two “snooze” requests were made over the course of the arm by a single patient, who responded both times after the additional reminder.

Four severely elevated blood pressures were sent to the physician responder, all from a single patient. This patient was diagnosed with preeclampsia with severe features on delivery admission, and her blood pressures normalized prior to discharge. All four “at risk” blood pressures were addressed within 24 hours of the text message. Due to persistently elevated diastolic blood pressures ranging from 110–120 mm Hg, she was started on hydrochlorothiazide 12.5 mg on day 6 of the cycle and monitored for additional days following cycle completion with improved blood pressures.

Cycle 6 - Snooze and Support Person

The patients in Cycle 5 were overall satisfied with their experience and did not provide any suggestions for change. However, we sought to see if integrating support persons into the protocol would affect engagement. Cycle 6 tested our hypothesis that patients would be more engaged if they had a self-identified support person reminding them to text their blood pressures. Patients provided the name of a support person to contact if a morning blood pressure was not received. Additionally, patients received the same “snooze” option as in Cycle 5. A total of five patients were enrolled in this cohort; one patient enrolled in the trial but did not send in any blood pressures despite daily reminders to both her and her support buddy. Only 2 additional buddy notifications were required in patients who did not send in a morning blood pressure reading and both times a subsequent blood pressure was sent. Two “snooze” requests were made over the course of the cycle by a single patient, who responded both times after the reminder.

Four of five patients in this cohort sent at least one blood pressure text on post-discharge day 1 or 2 (80%). Three patients (60%) also sent in at least one blood pressure on day 5, 6, or 7.

There were no significantly elevated blood pressures sent to the physician responder and no medications were initiated.

Post-Cycle Interviews

Overall, patients reported satisfaction with the text messaging system in their post-cycle interviews. The convenience of the intervention was acknowledged by many, including one patient who commented that “this was a lot better than having to pay for the bus and waiting for hours in some waiting room.” One patient also reported that the increased awareness was important, stating that “when [she] got home and realized that [her blood pressure] was still high, [she] did her own research and learned more about hypertension and preeclampsia.” Others reported that they still checked their blood pressure after the cycle, and “would have went longer than a week if they had asked me to.”

Discussions

Our results suggest that remote blood pressure monitoring via text message communication engages patients and shows promise as a convenient and effective means of hypertension surveillance in the immediate postpartum period, in accordance to ACOG guidelines. Additionally, we were able to test this monitoring system using inexpensive, rapid-cycle validation techniques. Although these techniques are insufficiently controlled and of inadequate statistical power for definitive results, they were able to provide quick evidence toward a pragmatic and workable solution to an important clinical problem within the specific clinical context of our practice, though the results are likely to generalize to other settings. We found varied compliance based on the different engagement strategies, and although no single cycle proved superior, overall patient participation was good and provides a basis for different texting options in future work. Developing a method that both engages patients and is streamlined for providers is critical to our ability to translate this recommendation into practice. Although we did not specifically test how the system works from a provider’s point of view, the study obstetricians believe that this would help and can be fit within the existing workflows of the practices at most institutions.

This rapid-cycle intervention study provides several additional lessons, as we were able to rapidly implement this on our unit and test several hypotheses related to patient engagement. Most patients found the text messaging system to be a convenient way to communicate with their obstetrician. Even when patients had prenatal care at other institutions and delivered at our hospital without a prior patient/physician relationship (n = 5), we were able to engage them in text messaging. However, there was some evidence of patient drop out over the course of the week, as patients were more likely to text in blood pressure in the first few days of the cycle than the last few days (Figure 2).

Other telemedicine interventions have been studied in maternity care and have had inconsistent results. The Cochrane review on telephone support for women during pregnancy and up to 6 weeks after birth found that interventions were mainly aimed at smoking cessation, breastfeeding continuation, preterm birth, and postpartum depression [19]. To date, none of the randomized trials in pregnancy or the postpartum period have focused on postpartum hypertension. The results of our interventions are encouraging and support the use of text messaging in obstetrical care, particularly in the postpartum period. While text messaging cannot provide all the information that can be obtained in a doctor’s visit, such as physical exam, urine dipsticks, and review of symptoms, it can identify the minority of patients that may need to be seen in the office based on the severity of their blood pressures.

While some cases of postpartum preeclampsia occur in the absence of peripartum disease, most readmitted patients are diagnosed with preeclampsia prior to delivery and readmission is due to worsening or persistence of disease and therefore, potentially preventable. These patients are the primary target of our intervention, as remote hypertension surveillance provides an opportunity to start or adjust medications and minimize both patient inconvenience and hospital cost of a readmission.

However, our feasibility study has some limitations. Despite overall patient satisfaction, acceptability, and compliance with text message monitoring of hypertension, the small sample size and qualitative nature of our cycles merits further pursuit and follow-up studies prior to implementation. Overall, we had only a small number of elevated blood pressures requiring intervention; however, this underscores the need to identify patients most at risk for persistent or delayed hypertension and the importance of developing a method of follow-up that engages all patients. Additionally, as patients were asked to both text in blood pressure values and also present for office visits, and therefore acted as their own control, it is not surprising that more patients were compliant with the simple texting method than standard of care; however, even when comparing texting compliance to historical attendance in our clinic of only 30%, our results remain promising.

While our results are encouraging, we believe it is important to test text messaging surveillance and patient compliance in a larger trial prior to implementing within the broader community. This study provides critical data to support the development of a HIPAA-compliant, automated monitoring system that can provide timely responses to patient texts using a provider derived response to blood pressure values. Future work includes the development of an automated hypertension tool as well as a randomized controlled trial to more rigorously compare office blood pressure visits to remote text message surveillance. If effective, use of text messaging technology may allow for an improved patient partnership and more robust follow-up data, especially in patients with less than optimal compliance, as well as the ability to improve maternal care and decrease morbidity and mortality.

Corresponding author: Adi Hirshberg, MD, Dept. of Maternal-Fetal Medicine, 2 Silverstein, 3400 Spruce St., Philadelphia, PA 19104, [email protected].

Funding/support: Supported by a Penn Medicine Innovation Accelerator grant.

Financial disclosures. None reported.

Nurse Jackie is an amazing woman: She’s a fantastically competent and compassionate ER nurse who will do anything for her patients, and she is far better than the caricature ER docs she works with who all care more about their designer shoes and designer egos then about their jobs. She’s a wife – at least in the early episodes – and mother to two adorable girls with a life that includes Mommy and Me tap dancing classes. She somehow juggles it all.

In her fictional life as the star of a Showtime series, “Jackie Peyton” – played by actress Edie Falco, formerly known for her role as Tony Soprano’s wife, Carmela – manages even more: She does it all while popping pain pills by the handful throughout the work day and snorting whatever there is to snort. The interesting thing about Jackie is that her drug habit never interferes with her ability to function. There are no episodes where she makes mistakes or falls asleep. She doesn’t get too wired and is rarely irritable, and she certainly doesn’t pass out from overdoses. She shows up at work on time and never falls off her tightrope of responsibilities in the busy All Saints Hospital ER of New York City.

Without the drugs, she gets ill, but with them, she just functions. And she doesn’t just hold her own with a busy life; she also juggles the secret life of what it takes to get her daily fix, including daily lunchtime sex with the hospital pharmacist, who provides her with pain medicines for her aching back and doesn’t initially know that she’s married with children.

By Season 6, her personal life has broken down, and her daughter Grace, now an angry teenager with her own difficulties and secret life, notes that mom Jackie is incredibly good at hiding her drug use, and that no one can tell when she’s using.

With each season, Jackie’s personal life unwinds a little more, but it’s not because of the effects constant pill-popping has on her behavior; it’s because of the difficulties she has obtaining the drugs. If she could go to the store and buy large amounts of oxycontin and whatever else she takes, she’d have no problem. Her cauldron, however, is filled with constant lies and deception and the secret lives she lives to obtain drugs and to avoid boiling in her own self-made addictive mess.

Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Care,” which was released last fall (Baltimore: Johns Hopkins University Press).

Nurse Jackie is an amazing woman: She’s a fantastically competent and compassionate ER nurse who will do anything for her patients, and she is far better than the caricature ER docs she works with who all care more about their designer shoes and designer egos then about their jobs. She’s a wife – at least in the early episodes – and mother to two adorable girls with a life that includes Mommy and Me tap dancing classes. She somehow juggles it all.

In her fictional life as the star of a Showtime series, “Jackie Peyton” – played by actress Edie Falco, formerly known for her role as Tony Soprano’s wife, Carmela – manages even more: She does it all while popping pain pills by the handful throughout the work day and snorting whatever there is to snort. The interesting thing about Jackie is that her drug habit never interferes with her ability to function. There are no episodes where she makes mistakes or falls asleep. She doesn’t get too wired and is rarely irritable, and she certainly doesn’t pass out from overdoses. She shows up at work on time and never falls off her tightrope of responsibilities in the busy All Saints Hospital ER of New York City.

Without the drugs, she gets ill, but with them, she just functions. And she doesn’t just hold her own with a busy life; she also juggles the secret life of what it takes to get her daily fix, including daily lunchtime sex with the hospital pharmacist, who provides her with pain medicines for her aching back and doesn’t initially know that she’s married with children.

By Season 6, her personal life has broken down, and her daughter Grace, now an angry teenager with her own difficulties and secret life, notes that mom Jackie is incredibly good at hiding her drug use, and that no one can tell when she’s using.

With each season, Jackie’s personal life unwinds a little more, but it’s not because of the effects constant pill-popping has on her behavior; it’s because of the difficulties she has obtaining the drugs. If she could go to the store and buy large amounts of oxycontin and whatever else she takes, she’d have no problem. Her cauldron, however, is filled with constant lies and deception and the secret lives she lives to obtain drugs and to avoid boiling in her own self-made addictive mess.

Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Care,” which was released last fall (Baltimore: Johns Hopkins University Press).

Nurse Jackie is an amazing woman: She’s a fantastically competent and compassionate ER nurse who will do anything for her patients, and she is far better than the caricature ER docs she works with who all care more about their designer shoes and designer egos then about their jobs. She’s a wife – at least in the early episodes – and mother to two adorable girls with a life that includes Mommy and Me tap dancing classes. She somehow juggles it all.

In her fictional life as the star of a Showtime series, “Jackie Peyton” – played by actress Edie Falco, formerly known for her role as Tony Soprano’s wife, Carmela – manages even more: She does it all while popping pain pills by the handful throughout the work day and snorting whatever there is to snort. The interesting thing about Jackie is that her drug habit never interferes with her ability to function. There are no episodes where she makes mistakes or falls asleep. She doesn’t get too wired and is rarely irritable, and she certainly doesn’t pass out from overdoses. She shows up at work on time and never falls off her tightrope of responsibilities in the busy All Saints Hospital ER of New York City.

Without the drugs, she gets ill, but with them, she just functions. And she doesn’t just hold her own with a busy life; she also juggles the secret life of what it takes to get her daily fix, including daily lunchtime sex with the hospital pharmacist, who provides her with pain medicines for her aching back and doesn’t initially know that she’s married with children.

By Season 6, her personal life has broken down, and her daughter Grace, now an angry teenager with her own difficulties and secret life, notes that mom Jackie is incredibly good at hiding her drug use, and that no one can tell when she’s using.

With each season, Jackie’s personal life unwinds a little more, but it’s not because of the effects constant pill-popping has on her behavior; it’s because of the difficulties she has obtaining the drugs. If she could go to the store and buy large amounts of oxycontin and whatever else she takes, she’d have no problem. Her cauldron, however, is filled with constant lies and deception and the secret lives she lives to obtain drugs and to avoid boiling in her own self-made addictive mess.

Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Care,” which was released last fall (Baltimore: Johns Hopkins University Press).

It’s 7:30 on a Tuesday evening, and you will be on call until 8 o’clock the next morning. You have already been in the office 9 hours. Usual start time is 8 a.m., but that extra hour at home is a perk you have earned by being on call tonight.

A quick glance at the schedule screen suggests that if nothing ugly crops up, you will finish seeing your last patient and be out the door and on your way home by 8:15 p.m. The phone has been quiet for the last half hour, but as you are making your quickstep transition between exam rooms, the nurse tells you that the receptionist has received a call from a very anxious mother who has just discovered that her 6-year-old has a fever of 103° F. The child didn’t eat any dinner and is now complaining that he has a sore throat. The mother is worried because the child had a couple of febrile seizures when he was a toddler, and she has heard of several cases of strep in his class at school.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics including “How to Say No to Your Toddler.” Email him at [email protected].

It’s 7:30 on a Tuesday evening, and you will be on call until 8 o’clock the next morning. You have already been in the office 9 hours. Usual start time is 8 a.m., but that extra hour at home is a perk you have earned by being on call tonight.

A quick glance at the schedule screen suggests that if nothing ugly crops up, you will finish seeing your last patient and be out the door and on your way home by 8:15 p.m. The phone has been quiet for the last half hour, but as you are making your quickstep transition between exam rooms, the nurse tells you that the receptionist has received a call from a very anxious mother who has just discovered that her 6-year-old has a fever of 103° F. The child didn’t eat any dinner and is now complaining that he has a sore throat. The mother is worried because the child had a couple of febrile seizures when he was a toddler, and she has heard of several cases of strep in his class at school.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics including “How to Say No to Your Toddler.” Email him at [email protected].

It’s 7:30 on a Tuesday evening, and you will be on call until 8 o’clock the next morning. You have already been in the office 9 hours. Usual start time is 8 a.m., but that extra hour at home is a perk you have earned by being on call tonight.

A quick glance at the schedule screen suggests that if nothing ugly crops up, you will finish seeing your last patient and be out the door and on your way home by 8:15 p.m. The phone has been quiet for the last half hour, but as you are making your quickstep transition between exam rooms, the nurse tells you that the receptionist has received a call from a very anxious mother who has just discovered that her 6-year-old has a fever of 103° F. The child didn’t eat any dinner and is now complaining that he has a sore throat. The mother is worried because the child had a couple of febrile seizures when he was a toddler, and she has heard of several cases of strep in his class at school.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics including “How to Say No to Your Toddler.” Email him at [email protected].

LAS VEGAS – Contrary to what some recent studies suggest, patients with complicated appendicitis may benefit from immediate surgery, with shorter hospital stays and fewer postoperative complications.

According to findings from a large database review, delaying the surgery for a complicated case is likely to result in worse patient outcomes, Matthew Symer, MD, said at the Association for Academic Surgery/Society of University Surgeons Academic Surgical Congress.

decade3d/Thinkstock

[email protected]

On Twitter @Alz_Gal

LAS VEGAS – Contrary to what some recent studies suggest, patients with complicated appendicitis may benefit from immediate surgery, with shorter hospital stays and fewer postoperative complications.

According to findings from a large database review, delaying the surgery for a complicated case is likely to result in worse patient outcomes, Matthew Symer, MD, said at the Association for Academic Surgery/Society of University Surgeons Academic Surgical Congress.

decade3d/Thinkstock

[email protected]

On Twitter @Alz_Gal

LAS VEGAS – Contrary to what some recent studies suggest, patients with complicated appendicitis may benefit from immediate surgery, with shorter hospital stays and fewer postoperative complications.

According to findings from a large database review, delaying the surgery for a complicated case is likely to result in worse patient outcomes, Matthew Symer, MD, said at the Association for Academic Surgery/Society of University Surgeons Academic Surgical Congress.

decade3d/Thinkstock

[email protected]

On Twitter @Alz_Gal

SNOWMASS, COLO. – The indication for primary prophylactic implantable cardioverter-defibrillator therapy in patients with nonischemic heart failure is likely to be downgraded in the next iteration of the ACC/AHA heart failure guidelines as a consequence of the negative results of the DANISH trial, William T. Abraham, MD, predicted at the Annual Cardiovascular Conference at Snowmass.

In addition to outlining where the guideline recommendations for implantable cardioverter-defibrillator (ICD) therapy stand today, and how they’re likely to change in response to the DANISH findings, he highlighted the latest patient selection criteria for cardiac resynchronization therapy (CRT), which have grown considerably more complicated over time.

Bruce Jancin/Frontline Medical News

[email protected]

SNOWMASS, COLO. – The indication for primary prophylactic implantable cardioverter-defibrillator therapy in patients with nonischemic heart failure is likely to be downgraded in the next iteration of the ACC/AHA heart failure guidelines as a consequence of the negative results of the DANISH trial, William T. Abraham, MD, predicted at the Annual Cardiovascular Conference at Snowmass.

In addition to outlining where the guideline recommendations for implantable cardioverter-defibrillator (ICD) therapy stand today, and how they’re likely to change in response to the DANISH findings, he highlighted the latest patient selection criteria for cardiac resynchronization therapy (CRT), which have grown considerably more complicated over time.

Bruce Jancin/Frontline Medical News

[email protected]

SNOWMASS, COLO. – The indication for primary prophylactic implantable cardioverter-defibrillator therapy in patients with nonischemic heart failure is likely to be downgraded in the next iteration of the ACC/AHA heart failure guidelines as a consequence of the negative results of the DANISH trial, William T. Abraham, MD, predicted at the Annual Cardiovascular Conference at Snowmass.

In addition to outlining where the guideline recommendations for implantable cardioverter-defibrillator (ICD) therapy stand today, and how they’re likely to change in response to the DANISH findings, he highlighted the latest patient selection criteria for cardiac resynchronization therapy (CRT), which have grown considerably more complicated over time.

Bruce Jancin/Frontline Medical News

[email protected]

Your first patient of the day is a 2½-year-old who has a runny nose and a cough. His mother has brought him in because his cough is more frequent and persistent than she is accustomed to hearing. He is happy and playful, and has a low-grade fever. You notice that he is slightly tachypneic, and you hear fine wheezes scattered throughout his lung fields. You also recall that at age 6 months, he was diagnosed with bronchiolitis but was never hospitalized.

Will you give him antibiotics and send him home with a nebulizer? Just the nebulizer? Just the antibiotics? Neither? We can debate those answers for hours, and you can plead for more information before you commit to an answer. But let’s skip over the question about what you are going to do and focus on what you are going to say. I want to know what diagnosis you are going to share with this mother.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics including “How to Say No to Your Toddler.” Email him at [email protected].

Your first patient of the day is a 2½-year-old who has a runny nose and a cough. His mother has brought him in because his cough is more frequent and persistent than she is accustomed to hearing. He is happy and playful, and has a low-grade fever. You notice that he is slightly tachypneic, and you hear fine wheezes scattered throughout his lung fields. You also recall that at age 6 months, he was diagnosed with bronchiolitis but was never hospitalized.

Will you give him antibiotics and send him home with a nebulizer? Just the nebulizer? Just the antibiotics? Neither? We can debate those answers for hours, and you can plead for more information before you commit to an answer. But let’s skip over the question about what you are going to do and focus on what you are going to say. I want to know what diagnosis you are going to share with this mother.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics including “How to Say No to Your Toddler.” Email him at [email protected].

Your first patient of the day is a 2½-year-old who has a runny nose and a cough. His mother has brought him in because his cough is more frequent and persistent than she is accustomed to hearing. He is happy and playful, and has a low-grade fever. You notice that he is slightly tachypneic, and you hear fine wheezes scattered throughout his lung fields. You also recall that at age 6 months, he was diagnosed with bronchiolitis but was never hospitalized.

Will you give him antibiotics and send him home with a nebulizer? Just the nebulizer? Just the antibiotics? Neither? We can debate those answers for hours, and you can plead for more information before you commit to an answer. But let’s skip over the question about what you are going to do and focus on what you are going to say. I want to know what diagnosis you are going to share with this mother.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics including “How to Say No to Your Toddler.” Email him at [email protected].

MIAMI – Ask patients about their hair during a general dermatology examination, recommend supplements backed by peer-reviewed studies when appropriate, and watch for a new trend – man bun traction alopecia.

These and other clinical pearls on hair loss come courtesy of Wendy E. Roberts, MD.

“Hair loss can be scary,” but if physicians diagnose the underlying cause and treat early, a number of existing and upcoming treatments can be effective, said Dr. Roberts, a dermatologist in private practice in Rancho Mirage, Calif. “Timing is very critical.”

Suggest supplements backed by science

Given the millions of online searches, it’s apparent that people continue to look for the latest solutions to treat or prevent further hair loss. But as with many “treatments” and “cures” touted online, caution is warranted – not every claim is backed by solid research, she said. “Go with supplements that do have peer review literature.”

For this reason, Dr. Roberts suggests considering the following three supplements for patients with hair loss:

• Nutrafol – “What I like about this supplement is it has ashwagandha, an Indian herb that reduces stress,” she said.

• Viviscal – This supplement has the marine extract AminoMar, which includes shark cartilage and oyster extract powder.

• Vitalize Hair – Its active ingredient, Redensyl, contains two molecules, Dr. Roberts said, one to boost metabolism of the hair follicle and the other to increase hair volume over time.

Application of platelet rich plasma is another option showing promise for hair loss. It works by activating hair bulb cells. “It kind of whispers to the hair: ‘Be young again.’ Many times it comes in at the original hair color – tell your patients to be prepared to see their hair color from childhood.” Dr. Roberts said.

Man bun alert

There is a new consideration in male hair loss based on changing hairstyles. “One thing that is trending: man bun traction alopecia. We see a lot of this in Southern California where I practice,” Dr. Roberts said. She showed meeting attendees the photo of a man with a tight hair bun whose hairline was starting to recede.

EzumeImages/Thinkstock

Basics to remember: differential diagnosis

When a patient presents with hair loss, things to consider in a differential diagnosis include chemical hair treatments, hairstyles that can cause traction alopecia, and behaviors such as compulsive hair pulling. Trichotillomania is on the increase. It affects approximately 2% of the population, but 90% of those are women, Dr. Roberts said. To diagnose, “look at the scalp and lower area near the nape of neck, especially in younger patients.”

She suggested that dermatologists show male patients the Norwood Scale illustrations of hair loss. The illustrations can help them understand when their hair loss is progressing over time, she added. For female patients with hair loss, the Ludwig Scale for hair loss in women can be very illustrative.

In the work-up of the patient, conduct a physical exam and consider overall health and nutritional status. Ask about family history as well, because relatives are the best window for insight into hair loss caused by genetics and aging, Dr. Roberts said.

Review patient medications. Older patients, in particular, often take multiple medications, which increases the likelihood for interactions or side effects leading to hair loss.

In addition, she had a few specific recommendations. “When you have male patient with hair loss taking Propecia [finasteride], talk to them about the dangers of exposure to a female partner and pregnancy in particular.” Also ask patients to bring in any supplements they are taking. Watch out for keratin supplements in patients with renal disease, she added, because elevated levels can be associated with kidney problems.

In terms of laboratory testing, consider checking for thyroid function, hormonal imbalance, and anemia. “The most overlooked is hemoglobin levels,” Dr. Roberts said, although anemia can cause hair loss in some patients.

Dr. Roberts is a speaker, consultant, investigator for and/or receives honoraria from Allergan, Colorescience, Galderma, Lytera, MDRejuvena, Restorsea, SkinMedica, Theraplex, Top MD Skincare, Valeant Pharmaceutical International, and Viviscal.

[email protected]

MIAMI – Ask patients about their hair during a general dermatology examination, recommend supplements backed by peer-reviewed studies when appropriate, and watch for a new trend – man bun traction alopecia.

These and other clinical pearls on hair loss come courtesy of Wendy E. Roberts, MD.

“Hair loss can be scary,” but if physicians diagnose the underlying cause and treat early, a number of existing and upcoming treatments can be effective, said Dr. Roberts, a dermatologist in private practice in Rancho Mirage, Calif. “Timing is very critical.”

Suggest supplements backed by science

Given the millions of online searches, it’s apparent that people continue to look for the latest solutions to treat or prevent further hair loss. But as with many “treatments” and “cures” touted online, caution is warranted – not every claim is backed by solid research, she said. “Go with supplements that do have peer review literature.”

For this reason, Dr. Roberts suggests considering the following three supplements for patients with hair loss:

• Nutrafol – “What I like about this supplement is it has ashwagandha, an Indian herb that reduces stress,” she said.

• Viviscal – This supplement has the marine extract AminoMar, which includes shark cartilage and oyster extract powder.

• Vitalize Hair – Its active ingredient, Redensyl, contains two molecules, Dr. Roberts said, one to boost metabolism of the hair follicle and the other to increase hair volume over time.

Application of platelet rich plasma is another option showing promise for hair loss. It works by activating hair bulb cells. “It kind of whispers to the hair: ‘Be young again.’ Many times it comes in at the original hair color – tell your patients to be prepared to see their hair color from childhood.” Dr. Roberts said.

Man bun alert

There is a new consideration in male hair loss based on changing hairstyles. “One thing that is trending: man bun traction alopecia. We see a lot of this in Southern California where I practice,” Dr. Roberts said. She showed meeting attendees the photo of a man with a tight hair bun whose hairline was starting to recede.

EzumeImages/Thinkstock

Basics to remember: differential diagnosis

When a patient presents with hair loss, things to consider in a differential diagnosis include chemical hair treatments, hairstyles that can cause traction alopecia, and behaviors such as compulsive hair pulling. Trichotillomania is on the increase. It affects approximately 2% of the population, but 90% of those are women, Dr. Roberts said. To diagnose, “look at the scalp and lower area near the nape of neck, especially in younger patients.”

She suggested that dermatologists show male patients the Norwood Scale illustrations of hair loss. The illustrations can help them understand when their hair loss is progressing over time, she added. For female patients with hair loss, the Ludwig Scale for hair loss in women can be very illustrative.

In the work-up of the patient, conduct a physical exam and consider overall health and nutritional status. Ask about family history as well, because relatives are the best window for insight into hair loss caused by genetics and aging, Dr. Roberts said.

Review patient medications. Older patients, in particular, often take multiple medications, which increases the likelihood for interactions or side effects leading to hair loss.

In addition, she had a few specific recommendations. “When you have male patient with hair loss taking Propecia [finasteride], talk to them about the dangers of exposure to a female partner and pregnancy in particular.” Also ask patients to bring in any supplements they are taking. Watch out for keratin supplements in patients with renal disease, she added, because elevated levels can be associated with kidney problems.

In terms of laboratory testing, consider checking for thyroid function, hormonal imbalance, and anemia. “The most overlooked is hemoglobin levels,” Dr. Roberts said, although anemia can cause hair loss in some patients.

Dr. Roberts is a speaker, consultant, investigator for and/or receives honoraria from Allergan, Colorescience, Galderma, Lytera, MDRejuvena, Restorsea, SkinMedica, Theraplex, Top MD Skincare, Valeant Pharmaceutical International, and Viviscal.

[email protected]

MIAMI – Ask patients about their hair during a general dermatology examination, recommend supplements backed by peer-reviewed studies when appropriate, and watch for a new trend – man bun traction alopecia.

These and other clinical pearls on hair loss come courtesy of Wendy E. Roberts, MD.

“Hair loss can be scary,” but if physicians diagnose the underlying cause and treat early, a number of existing and upcoming treatments can be effective, said Dr. Roberts, a dermatologist in private practice in Rancho Mirage, Calif. “Timing is very critical.”

Suggest supplements backed by science

Given the millions of online searches, it’s apparent that people continue to look for the latest solutions to treat or prevent further hair loss. But as with many “treatments” and “cures” touted online, caution is warranted – not every claim is backed by solid research, she said. “Go with supplements that do have peer review literature.”

For this reason, Dr. Roberts suggests considering the following three supplements for patients with hair loss:

• Nutrafol – “What I like about this supplement is it has ashwagandha, an Indian herb that reduces stress,” she said.

• Viviscal – This supplement has the marine extract AminoMar, which includes shark cartilage and oyster extract powder.

• Vitalize Hair – Its active ingredient, Redensyl, contains two molecules, Dr. Roberts said, one to boost metabolism of the hair follicle and the other to increase hair volume over time.

Application of platelet rich plasma is another option showing promise for hair loss. It works by activating hair bulb cells. “It kind of whispers to the hair: ‘Be young again.’ Many times it comes in at the original hair color – tell your patients to be prepared to see their hair color from childhood.” Dr. Roberts said.

Man bun alert

There is a new consideration in male hair loss based on changing hairstyles. “One thing that is trending: man bun traction alopecia. We see a lot of this in Southern California where I practice,” Dr. Roberts said. She showed meeting attendees the photo of a man with a tight hair bun whose hairline was starting to recede.

EzumeImages/Thinkstock

Basics to remember: differential diagnosis

When a patient presents with hair loss, things to consider in a differential diagnosis include chemical hair treatments, hairstyles that can cause traction alopecia, and behaviors such as compulsive hair pulling. Trichotillomania is on the increase. It affects approximately 2% of the population, but 90% of those are women, Dr. Roberts said. To diagnose, “look at the scalp and lower area near the nape of neck, especially in younger patients.”

She suggested that dermatologists show male patients the Norwood Scale illustrations of hair loss. The illustrations can help them understand when their hair loss is progressing over time, she added. For female patients with hair loss, the Ludwig Scale for hair loss in women can be very illustrative.

In the work-up of the patient, conduct a physical exam and consider overall health and nutritional status. Ask about family history as well, because relatives are the best window for insight into hair loss caused by genetics and aging, Dr. Roberts said.

Review patient medications. Older patients, in particular, often take multiple medications, which increases the likelihood for interactions or side effects leading to hair loss.

In addition, she had a few specific recommendations. “When you have male patient with hair loss taking Propecia [finasteride], talk to them about the dangers of exposure to a female partner and pregnancy in particular.” Also ask patients to bring in any supplements they are taking. Watch out for keratin supplements in patients with renal disease, she added, because elevated levels can be associated with kidney problems.

In terms of laboratory testing, consider checking for thyroid function, hormonal imbalance, and anemia. “The most overlooked is hemoglobin levels,” Dr. Roberts said, although anemia can cause hair loss in some patients.

Dr. Roberts is a speaker, consultant, investigator for and/or receives honoraria from Allergan, Colorescience, Galderma, Lytera, MDRejuvena, Restorsea, SkinMedica, Theraplex, Top MD Skincare, Valeant Pharmaceutical International, and Viviscal.

[email protected]