Research Spotlight

McCullough, P. A. (2019). “Treatment of Orthostatic Hypotension Due to Autonomic Dysfunction (Neurogenic Orthostatic Hypotension) in a Patient with Cardiovascular Disease and Parkinson’s Disease.” Cardiol Ther 8(1): 145-150.

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INTRODUCTION: The prevalence of neurogenic orthostatic hypotension (nOH) increases with age and is associated with autonomic failure in neurodegenerative diseases (e.g., Parkinson’s disease). Symptoms can interfere with daily activities that require standing or walking and can increase risk of falls and related morbidity. Many patients with nOH have or develop cardiovascular comorbidities that can predate nOH symptoms or may arise as a result of autonomic dysregulation. In this report, we describe a complicated case of a patient with cardiovascular disease and Parkinson’s disease who presented with orthostatic symptoms. CASE REPORT: A 78-year-old man with a history of coronary heart disease, class III heart failure, cardiac cachexia, long-standing persistent atrial fibrillation (AF), Hodgkin’s lymphoma, and Parkinson’s disease presented with weakness, dizziness, presyncope, fatigue, and inability to stand. Orthostatic blood pressure (BP) measurements revealed a seated BP of 120/70 mmHg that decreased to 60/40 mmHg upon standing, accompanied by a slight increase in heart rate from 70 to 74 beats per minute. He was diagnosed with nOH and prescribed droxidopa (titrated to 600 mg three times daily). Treatment with droxidopa improved the patient’s ability to stand and his orthostatic BP. CONCLUSION: Droxidopa is approved by the US Food and Drug Administration to treat symptomatic nOH and is not contraindicated in patients with cardiovascular conditions. In this case, treatment with droxidopa improved the patient’s orthostatic tolerance and, importantly, did not change the patient’s rate-controlled AF or his symptoms of class IV heart failure. Because symptoms associated with nOH can be detrimental to patient safety and mobility, it is critical to screen for and treat patients with nOH, even when there are cardiovascular comorbidities. FUNDING: Editorial support and article processing charges were funded by Lundbeck. Plain language summary available for this article.

Matza, L. S., J. E. Brazier, K. D. Stewart, L. Pinto, R. H. Bender, L. Kircik, J. Jordan, K. J. Kim, A. Mutebi, H. N. Viswanathan and A. Menter (2019). “Developing a preference-based utility scoring algorithm for the Psoriasis Area Severity Index (PASI).” J Med Econ Jun 4:1-20. [Epub ahead of print].

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Introduction. It is challenging to identify health state utilities associated with psoriasis because generic preference-based measures may not capture the impact of dermatological symptoms. The Psoriasis Area Severity Index (PASI) is one of the most commonly used psoriasis rating scales in clinical trials. The purpose of this study was to develop a utility scoring algorithm for the PASI. Methods. Forty health states were developed based on PASI scores of 40 clinical trial patients. Health states were valued in time trade-off interviews with UK general population participants. Regression models were conducted to crosswalk from PASI scores to utilities (e.g., OLS linear, random effects, mean, robust, spline, quadratic). Results A total of 245 participants completed utility interviews (51.4% female; mean age = 45.3y). Models predicting utility based on the four PASI location scores (head, upper limbs, trunk, lower limbs) had better fit/accuracy (e.g., R(2), mean absolute error [MAE]) than models using the PASI total score. Head/upper limb scores were more strongly associated with utility than trunk/lower limb. The recommended model is the OLS linear model based on the four PASI location scores (R(2) = 0.13; MAE =0.03). An alternative is recommended for situations when it is necessary to estimate utility based on the PASI total score. Conclusions. The recommended scoring algorithm may be used to estimate utilities based on PASI scores of any treatment group with psoriasis. Because the PASI is commonly used in psoriasis clinical trials, this scoring algorithm greatly expands options for quantifying treatment outcomes in cost-effectiveness analyses of psoriasis therapies. Results indicate that psoriasis of the head/upper limbs could be more important than trunk/lower limbs, suggesting reconsideration of the standard PASI scoring approach.

Mack, M. J. and G. W. Stone (2019). “Response to Letters re: The COAPT Trial.” Cardiovasc Revasc Med 20(6): 531-532.

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The COAPT trial was a landmark study that demonstrated for the first time that correction of secondary or functional mitral regurgitation (MR) results in significant clinical benefits in patients with heart failure. The addition of the MitraClip to maximally tolerated guideline-directed medical therapy (GDMT) resulted in a 47% reduction in hospitalization for heart failure, the primary endpoint at two years. In addition, there were significant 2-year improvements in survival, quality-of-life and exercise performance. We appreciate the great interest generated by the COAPT outcomes as reflected by the letters to the editor in this issue. They raise some salient points that we would like to address. Khan et al. note that in COAPT, there was significant up-titration of both beta-blockers and mineralocorticoid receptor antagonists (MRA) during follow-up in the device arm. The protocol intent was to maintain GDMT in both arms, and as reported, there were few major increases or reductions in medical therapy in both groups. However, MR reduction by the MitraClip increases cardiac output and blood pressure, enabling up-titration of medical therapy in some patients. These medication changes, which might be expected in real-world practice, may have contributed in small part to the therapeutic benefit in the device arm. However, we do not agree with the authors that a double-blinded sham-controlled study is required to mitigate this potential “bias” (which is actually a response to improved hemodynamics, not bias). The beta-blocker increase was transient (1-year timepoint only), and the MRA difference was small and not significant. Nitrate use at 1 and 2 years was actually more common in the control arm. These modest changes in medications cannot explain the marked absolute benefits of MR reduction observed in COAPT (number needed-to-treat 3 and 6 patients, respectively, to prevent one hospitalization and save one life within 2 years). Given these outcomes, it would be both unfeasible and unethical to conduct a sham-controlled study in which a group of patients meeting COAPT-eligibility criteria were not offered active treatment. (Excerpt from text, p. 531; no abstract available.)

Law, L. H., D. K. Wilson, S. M. St George, H. Kitzman and C. J. Kipp (2019). “Families Improving Together (FIT) for weight loss: a resource for translation of a positive climate-based intervention into community settings.” Transl Behav Med. Jun 5. [Epub ahead of print].

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Climate-based weight loss interventions, or those that foster a nurturing family environment, address important ecological influences typically ignored by the traditional biomedical treatments. Promoting a climate characterized by positive communication, autonomy support, and parental warmth supports adolescents in making healthy behavioral changes. In addition, encouraging these skills within the family may have additional benefits of improved family functioning and other mental and physical health outcomes. Although several programs have identified essential elements and established the evidence base for the efficacy of these interventions, few have offered resources for the translation of these constructs from theoretical concepts to tangible practice. This paper provides strategies and resources utilized in the Families Improving Together (FIT) for weight loss randomized controlled trial to create a warm, supportive climate characterized by positive communication within the parent-child relationship. Detailed descriptions of how Project FIT emphasized these constructs through facilitator training, intervention curriculum, and process evaluation are provided as a resource for clinical and community interventions. Researchers are encouraged to provide resources to promote translation of evidence-based interventions for programs aiming to utilize a positive climate-based family approach for lifestyle modification.

Kenedi, H., J. Campbell-Vance, J. Reynolds, M. Foreman, C. Dollaghan, D. Graybeal, A. M. Warren and M. Bennett (2019). “Implementation and Analysis of a Free Water Protocol in Acute Trauma and Stroke Patients.” Crit Care Nurse 39(3): e9-e17.

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BACKGROUND: Free water protocols allow patients who aspirate thin liquids and meet eligibility criteria to have access to water or ice according to specific guidelines. Limited research is available concerning free water protocols in acute care settings. OBJECTIVES: To compare rates of positive clinical outcomes and negative clinical indicators of a free water protocol in the acute care setting and to continue monitoring participants discharged into the hospital system’s rehabilitation setting. Positive clinical outcomes were diet upgrade, fewer days to diet upgrade, and fewer days in the study. Negative clinical indicators were pneumonia, intubation, and diet downgrade. METHODS: A multidisciplinary team developed and implemented a free water protocol. All eligible stroke and trauma patients (n = 104) treated over a 3-year period were randomly assigned to an experimental group with access to water and ice or a control group without such access. Trained study staff recorded data on positive outcomes and negative indicators; statistical analyses were conducted with blinding. RESULTS: No significant group differences in positive outcomes were found (all P values were > .40). Negative clinical indicators were too infrequent to allow for statistical comparison of the 2 groups. Statistical analyses could not be conducted on the small number (n = 15) of patients followed into rehabilitation, but no negative clinical indicators occurred in these patients. CONCLUSIONS: Larger-scale studies are needed to reach decisive conclusions on the positive outcomes and negative indicators of a free water protocol in the acute care setting.