The Impact of Nonpharmacological Interventions on Patient Experience, Opioid Use, and Health Care Utilization in Adult Cardiac Surgery Patients: Protocol for a Mixed Methods Study.

BACKGROUND: Despite pharmacological treatments, patients undergoing cardiac surgery experience severe anxiety and pain, which adversely affect outcomes. Previous work examining pediatric and nonsurgical adult patients has documented the effectiveness of inexpensive, nonpharmacological techniques to reduce anxiety and pain as well as health care costs and length of hospitalization. However, the impact of nonpharmacological interventions administered by a dedicated comfort coach has not been evaluated in an adult surgical setting. OBJECTIVE: This trial aims to assess whether nonpharmacological interventions administered by a trained comfort coach affect patient experience, opioid use, and health care utilization compared with usual care in adult cardiac surgery patients. This study has 3 specific aims: assess the effect of a comfort coach on patient experience, measure differences in inpatient and outpatient opioid use and postoperative health care utilization, and qualitatively evaluate the comfort coach intervention. METHODS: To address these aims, we will perform a prospective, randomized controlled trial of 154 adult cardiac surgery patients at Michigan Medicine. Opioid-naive patients undergoing first-time, elective cardiac surgery via sternotomy will be randomized to undergo targeted interventions from a comfort coach (intervention) versus usual care (control). The individualized comfort coach interventions will be administered at 6 points: preoperative outpatient clinic, preoperative care unit on the day of surgery, extubation, chest tube removal, hospital discharge, and 30-day clinic follow-up. To address aim 1, we will examine the effect of a comfort coach on perioperative anxiety, self-reported pain, functional status, and patient satisfaction through validated surveys administered at preoperative outpatient clinic, discharge, 30-day follow-up, and 90-day follow-up. For aim 2, we will record inpatient opioid use and collect postdischarge opioid use and pain-related outcomes through an 11-item questionnaire administered at the 30-day follow-up. Hospital length of stay, readmission, number of days in an extended care facility, emergency room, urgent care, and an unplanned doctor's office visit will be recorded as the primary composite endpoint defined as total days spent at home within the first 30 days after surgery. For aim 3, we will perform semistructured interviews with patients in the intervention arm to understand the comfort coach intervention through a thematic analysis. RESULTS: This trial, funded by Blue Cross Blue Shield of Michigan Foundation in 2019, is presently enrolling patients with anticipated manuscript submissions from our primary aims targeted for the end of 2020. CONCLUSIONS: Data generated from this mixed methods study will highlight effective nonpharmacological techniques and support a multidisciplinary approach to perioperative care during the adult cardiac surgery patient experience. This study's findings may serve as the foundation for a subsequent multicenter trial and broader dissemination of these techniques to other types of surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT04051021; https://clinicaltrials.gov/ct2/show/NCT04051021. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/21350.

Efficacy and safety of latanoprost versus travoprost in exfoliative glaucoma patients.

OBJECTIVE: To evaluate 24-hour intraocular pressure (IOP) efficacy of latanoprost versus travoprost, each given every evening, in exfoliative glaucoma patients. DESIGN: Prospective, observer-masked, crossover comparison. PARTICIPANTS: Forty patients with exfoliation glaucoma. METHODS: Patients with a pressure of >24 mmHg were randomized to latanoprost or travoprost for an 8-week treatment period after a 6-week medicine-free period. Patients were then switched to the opposite treatment for the second period. At untreated baseline and at the end of each treatment period the IOP was measured at 6 am, 10 am, 2 pm, 6 pm, 10 pm, and 2 am. MAIN OUTCOME MEASURE: Diurnal IOP. RESULTS: The mean 24-hour IOP was 25.1+/-2.5 mmHg at baseline, 17.8+/-2.1 mmHg on latanoprost, and 17.3+/-2.2 mmHg on travoprost (P = 0.001). Individual time points were similar between treatments, except at 6 pm when travoprost provided lower IOP (16.7+/-2.6 vs 17.9+/-2.5 mmHg, P<0.001). Adverse events showed more conjunctival hyperemia with travoprost (n = 15) than latanoprost (n = 6; P = 0.03). CONCLUSIONS: Latanoprost and travoprost both significantly reduce the 24-hour IOP from baseline in exfoliative glaucoma, but travoprost may demonstrate a greater hypotensive efficacy in the late afternoon.

The clinical impact and incidence of periocular pigmentation associated with either latanoprost or bimatoprost therapy.

PURPOSE: To evaluate the incidence and characteristics of periocular pigmentation with latanoprost versus bimatoprost. METHODS: A retrospective, active-controlled comparison of consecutive patients treated with latanoprost or bimatoprost for 12 months evaluating patients to determine the incidence, characteristics, and reversibility of periocular pigmentation. RESULTS: Periocular pigmentation was found in 1% patients treated with latanoprost and 6% patients treated with bimatoprost within 12 months of beginning treatment (p = 0.004). CONCLUSIONS: This study suggests that periocular pigmentation may develop after treatment with latanoprost or bimatoprost.

24-hour intraocular pressure control obtained with evening- versus morning-dosed travoprost in primary open-angle glaucoma.

PURPOSE: To evaluate the quality of 24-hour intraocular pressure (IOP) control between morning- and evening-dosed travoprost in primary open-angle glaucoma patients. DESIGN: Prospective, crossover, double-masked comparison. METHODS: After a 6-week medicine-free period, 33 patients were randomized to receive travoprost dosed in the morning or evening. After 8 weeks of treatment, a 24-hour IOP curve was performed at 6 am, 10 am, 2 pm, 6 pm, 10 pm, and 2 am. Patients were then treated with the opposite dosing regimen for another 8 weeks, after which the 24-hour IOP curve was repeated. MAIN OUTCOME MEASURES: Twenty-four-hour IOP. RESULTS: The untreated mean 24-hour IOP was 23.6+/-2.0 mmHg. There were no differences for mean 24-hour IOP between the morning (17.5+/-1.9 mmHg) and evening (17.3+/-1.9 mmHg) dosings (P = 0.7). At 10 am, the evening dosing provided a statistically lower IOP (17.2+/-2.1 mmHg) than the morning dosing (19.1+/-2.5 mmHg) (P = 0.02). Evening dosing demonstrated a statistically lower 24-hour fluctuation of IOP (3.2+/-1.0 mmHg) than morning dosing (4.0+/-1.5 mmHg) (P = 0.01). Safety was similar, with conjunctival hyperemia being the most common adverse event (n = 9 [27% for morning dosing] and n = 11 [33% for evening dosing], P = 0.6). CONCLUSIONS: This study suggests that both morning and evening dosings of travoprost provide effective 24-hour IOP reduction. However, the evening dosing of travoprost demonstrates slightly greater daytime efficacy, with a narrower range of 24-hour pressure.

24-hour intraocular pressure control with maximum medical therapy compared with surgery in patients with advanced open-angle glaucoma.

PURPOSE: The purpose of this study was to evaluate 24-hour intraocular pressure (IOP) control in patients with moderate to severe open-angle glaucoma treated by trabeculectomy and mitomycin C versus maximum tolerated medical therapy. DESIGN: Prospective observational study. PARTICIPANTS: Thirty surgical patients and 30 medically treated patients with advanced glaucoma. METHODS: Patients successfully treated with initial trabeculectomy or patients considered successfully treated on maximum tolerated medical therapy (2-4 medicines) were enrolled. We performed IOP measurements at 6 am, 10 am, 2 pm, 6 pm, 10 pm, and 2 am. Patients were matched by IOP +/- 1 mmHg at 10 am. MAIN OUTCOME MEASURES: A 24-hour IOP control. RESULTS: The surgical patients had a mean diurnal IOP of 12.1+/-2.2 versus 13.5+/-2.0 mmHg for the matched medically treated patients (P = 0.0001). The average maximum IOP for the surgical group was 13.4+/-2.3 and 16.3+/-3.2 mm Hg for the medical group (P<0.0001). The 24-hour range of IOP for the surgical group was 2.3+/-0.8 and 4.8+/-2.3 mmHg for the medical group (P<0.0001). Except at 10 am (P = 0.5), the surgical group had a statistically lower IOP at each measured time point. Eleven (37%) patients in the medically treated group, and none in the surgically treated group, had peak IOPs > or = 18 mmHg. The majority of peak IOPs (10 of 11) occurred outside of normal office hours. CONCLUSIONS: This study suggests that a well-functioning trabeculectomy provides a statistically lower mean, peak, and range of IOP for the 24-hour day than maximum tolerated medical therapy in advanced glaucoma patients.

24-Hour control with a latanoprost-timolol fixed combination vs timolol alone.

OBJECTIVE: To evaluate 24-hour intraocular pressure (IOP) control with an evening-dosed latanoprost-timolol maleate fixed combination vs timolol alone in patients with primary open-angle glaucoma. METHODS: After a medicine-free period, qualified patients were randomized to either placebo dosed in the morning with a latanoprost-timolol fixed combination dosed in the evening or timolol alone dosed twice daily for 8 weeks. Patients were then switched to the opposite treatment for 8 weeks. At baseline and at the end of each treatment period, patients underwent IOP measurements. RESULTS: Both treatments reduced the IOP from untreated baseline at each time point and for the 24-hour curve (P<.001). When treatments were compared, the latanoprost-timolol fixed combination decreased the IOP more than timolol alone at each time point and for the 24-hour curve (2.9 mm Hg), and provided a lower absolute IOP at each time point (P<.001) and for the range (fluctuation) in IOP (P = .003) and for the 24-hour curve. Several adverse effects were observed more often with the latanoprost-timolol fixed combination, including ocular stinging (P = .05), conjunctival hyperemia (P = .02), and ocular itching (P = .04). CONCLUSION: The evening-dosed latanoprost-timolol fixed combination may provide better IOP control than timolol alone over 24 hours and may demonstrate a narrower range of IOP fluctuation in patients with primary open-angle glaucoma.

Mean intraocular pressure and progression based on corneal thickness in primary open-angle glaucoma.

PURPOSE: The aim of this study was to evaluate the association of corneal thickness on the incidence of glaucomatous progression at individual levels of intraocular pressure. METHODS: A retrospective, noninterventional evaluation of patients with primary open-angle glaucoma who were either stable over 5 years or had glaucomatous progression before 5 years of follow-up was performed. Each patient had central thickness corneal measurements documented. RESULTS: We included 310 patients in this study. Patients with thicker (at least 0.571 mm, n = 77) and mid-range corneas (0.511-0.570 mm, n = 177) progressed in 14% (n = 11) and 18% (n = 31) of cases, respectively. The progression rate for patients with a mean pressure of less than 17 mmHg in both groups was 12%-13%. In contrast, the progression rate in patients with 18 mmHg or higher was 23% and 16% in the mid-range and thick corneal groups, respectively. In patients with thinner corneas (equal to or less than 0.510 mm, n = 56), the progression rate was 32% (n = 18). The progression rate was 60% (12 of 20) with mean pressures of at least 18 mmHg or higher, but 18% with mean pressures equal to or less than 17 mmHg. Univariant (P = 0.05), but not multivariant, analysis showed that corneal thickness was a risk factor for progression. CONCLUSIONS: This study suggests that the reduction of intraocular pressure helps to prevent progression in patients with primary open-angle glaucoma. However, for patients with thinner corneas, pressure reduction may potentially be of even greater importance to help avoid glaucomatous progression. Future study should clarify potential variables associated with thin corneas and glaucomatous progression.

Latanoprost 0.005% versus bimatoprost 0.03% in primary open-angle glaucoma patients.

OBJECTIVE: To evaluate latanoprost versus bimatoprost given each evening over the 24-hour diurnal curve. DESIGN: Double-masked, 2-center, crossover comparison. PARTICIPANTS: Forty-two of 44 patients with primary open-angle glaucoma (POAG) completed the study. METHODS: Consecutive patients were not treated during a baseline 24-hour curve after a glaucoma medicine-free period. They then were randomized to either latanoprost or bimatoprost for a 7-week treatment period. Diurnal curve intraocular pressures (IOPs) were measured at treatment period end at 2 am, 6 am, 10 am, 2 pm, 6 pm, and 10 pm. After the first treatment period, patients were changed to the opposite medicine without a medicine-free period. Diurnal curve measurements were performed again at the end of the second 7-week treatment period. MAIN OUTCOME MEASURE: The 24-hour diurnal IOP. RESULTS: On the last day of treatment, mean 24-hour IOPs were 17.3+/-2.8 mmHg for latanoprost and 16.7+/-2.4 mmHg for bimatoprost (P = 0.01). The 6 pm individual time point for IOP was statistically lower for bimatoprost after a Bonferroni correction (P = 0.008). The largest IOP difference at any time point was 0.9 mmHg at 6 pm. The most common side effect was conjunctival hyperemia, which occurred less with latanoprost (n = 6) than with bimatoprost (n = 15) (P = 0.004). Two patients had their treatments discontinued while on bimatoprost, one due to conjunctival hyperemia and the other due to ocular intolerance. CONCLUSION: This study indicates that the 24-hour diurnal IOP is statistically lower in POAG with bimatoprost, compared with latanoprost, among patients who tolerated bimatoprost. However, the IOP difference between groups was small and may not be clinically meaningful. In contrast, conjunctival hyperemia seems statistically greater with bimatoprost. The exact clinical importance of conjunctival hyperemia, if any, needs to be clarified further.

Twenty-four-hour control with latanoprost-timolol-fixed combination therapy vs latanoprost therapy.

OBJECTIVE: To evaluate the 24-hour efficacy and safety of the latanoprost-timolol maleate-fixed combination vs latanoprost therapy in patients with primary open-angle glaucoma. METHODS: A prospective, observer-masked, crossover, active-controlled, randomized comparison in which after a 6-week medicine-free period, patients were randomized to either latanoprost-timolol-fixed combination therapy or latanoprost therapy, both dosed once each evening, alone for 8 weeks. Patients were then switched to the opposite treatment for 8 weeks. At the end of the washout and treatment periods, a 24-hour diurnal curve was performed. RESULTS: The baseline untreated mean +/- SD diurnal curve in 37 patients who completed the study was 24.2 +/- 2.0 mm Hg. The mean diurnal curve was 19.2 +/- 2.6 mm Hg for those who received latanoprost therapy alone and 16.7 +/- 2.1 mm Hg for those who received the fixed combination therapy (P<.001). The fixed combination therapy also provided a lower absolute intraocular pressure level (1.5-2.9 mm Hg, P<.001) and a greater intraocular pressure reduction from the untreated baseline (P<.001). Stinging was statistically lower with latanoprost therapy alone (P = .04), but itching was statistically increased compared with the fixed combination therapy (P = .04). CONCLUSION: The result of this study suggests that the latanoprost-timolol-fixed combination compared with latanoprost therapy alone provides improved intraocular pressure reduction over the 24-hour diurnal curve and for each individual time point in patients with primary open-angle glaucoma.

Factors associated with long-term progression or stability in exfoliation glaucoma.

OBJECTIVE: To evaluate the effect of intraocular pressure (IOP) reduction on long-term progression or stability in patients with exfoliation glaucoma. DESIGN: Multicenter (Greece, Spain, Russia, and Hungary), retrospective analysis. METHODS: Medical record analysis of 167 patients with at least 5 years of follow-up, who were stable (n = 85) or whose condition had progressed (n = 82) after the beginning of the follow-up period. RESULTS: The mean +/- SD IOP was 18.1 +/- 2.6 mm Hg in the stable group and 20.1 +/- 4.3 mm Hg in the progressed group (P<.001). The mean +/- SD follow-up time was 6.1 +/- 2.3 years for the stable group and 3.4 +/- 1.7 years for the progressed group. The mean SD for each patient's average IOP was 2.9 mm Hg for the stable group and 4.6 mm Hg for the progressed group (P<.001). Twenty-eight percent of patients who had a mean IOP of 17 mm Hg or lower, 43% of those with an IOP of 18 to 19 mm Hg, and 70% of those with an IOP of 20 mm Hg or higher progressed. Progressed patients had statistically greater optic disc damage at baseline and more medication changes and trabeculectomies during follow-up than stable patients (P<.05). CONCLUSION: This study suggests that IOP reduction helps to prevent glaucoma progression in patients with exfoliation glaucoma, although it does not guarantee the prevention or worsening of the disease.

Can patients guess their intraocular pressure?

PURPOSE: To determine whether patients can guess their intraocular pressure (IOP). DESIGN: Patient survey. METHODS: We asked consecutive patients to guess their IOP and then indicate the IOP and the symptoms that allowed them to guess. RESULTS: Of 132 patients, 22 (17%) believed they could guess their IOP, usually based on a periocular symptom (n = 20, 91%). Nine of these patients (45%) correctly identified whether they were below or above the pressure indicated by the symptom. In two patients who required no symptoms to guess and in nine whose IOP was above their symptom threshold, the mean difference of the guessed IOP from the actual IOP did not differ (+/- 3.3 mm Hg) from that of control patients (+/- 2.1 mm Hg, n = 50; r =.19). CONCLUSIONS: Patients who believe they can guess their IOP appear as often inaccurate as accurate in assessing their IOP related to a symptom threshold and as accurate as patients who claim they cannot guess their IOP.

Dropout rates for intent-to-treat and per protocol analyses.

PURPOSE: To describe dropout rates for the intent-to-treat and per protocol analyses from prospective clinical trials. METHODS: Review of prospective multi-center parallel studies of 100 patients or more from 1996 onwards. RESULTS: We identified 33 articles (70 treatment arms) that fit the criteria for this study. No statistical differences in dropout rates were observed among drug classes for either the intent-to-treat (P =.075) or per protocol analyses (P =.40). A difference was observed in the percent dropout rate for the intent-to-treat analyses decreasing with the length of the study (P <.0001). This finding was not observed by the number of study visits (P =.44). However, a statistically greater percent dropout rate was observed for the per protocol analyses increasing with the length of the study (P =.034) and number of study visits (P =.01). No statistical differences were observed or with increasing sample size of the study for either the intent-to-treat or per protocol analyses (P >.05). CONCLUSIONS: Known discontinuation rates for per protocol and intent-to-treat analyses may help in planning sample sizes for future clinical trials.

Corneal punctate staining with latanoprost, bimatoprost, and travoprost in healthy subjects.

PURPOSE: To evaluate short-term conjunctival and corneal punctate staining with latanoprost, bimatoprost, and travoprost in healthy individuals. MATERIALS AND METHODS: A single centered, active-controlled, three-period crossover comparison that evaluated conjunctival and corneal punctate staining, by grade and individual stains, in healthy subjects after dosing for five days in one eye with latanoprost, bimatoprost, or travoprost. Staining was evaluated at 24-hour trough (Hour 0) and at Hour 1 after dosing. RESULTS: Twenty-eight subjects completed this study. This study found that there was no significant difference by ANOVA for the number of individual corneal punctate stains either at trough (latanoprost 22.6 +/- 25.4, bimatoprost 16.8 +/- 25.6, and travoprost 21.1 +/- 26.0 mm Hg) (P = 0.33) or at 1 hour after dosing (latanoprost 23.8 +/- 26.3 bimatoprost 18.2 +/- 25.2, and travoprost 26.1 +/- 26.1 mm Hg) (P = 0.75) among treatment groups. No significant differences existed among treatment groups in the study eye compared with the non-study eye or to the study eye at Hour 0 or Hour 1 or to the period initiation or baseline visits (P > 0.05). Several significantly different comparisons, inconsistent in nature, were observed for the nasal and temporal conjunctival staining between the treatment groups. There were no differences in unsolicited or solicited adverse events between groups. CONCLUSION: This study suggests that, in healthy subjects after short-term treatment, latanoprost, bimatoprost, and travoprost demonstrate generally similar ocular surface epithelial staining characteristics.

A persistency and economic analysis of latanoprost, bimatoprost, or beta-blockers in patients with open-angle glaucoma or ocular hypertension.

PURPOSE: The aim of this study was to evaluate differences in the persistency and treatment costs for latanoprost, bimatoprost, or beta-blockers in open-angle glaucoma or ocular hypertensive patients. METHODS: This study was a retrospective, multicenter, parallel, active-controlled comparison of patients who were prescribed with ocular hypotensive monotherapy between September 1996 and August 2002. RESULTS: 1,182 patients were included. The Kaplan Meier life table analysis showed that latanoprost was continued longest among the groups for the first year of therapy (p=0.02). A significant difference existed between groups in the final intraocular pressure for latanoprost (17.3+/-3.9, N=357), for bimatoprost (18.0+/-3.6, N=146), and for the beta-blockers (17.9+/-3.7, N=335) (p=<0.0001). The average number of visits was statistically higher for beta-blockers (3.3), compared to latanoprost (2.9) and bimatoprost (3.1) (p=0.01). Further, the mean number of medicine changes was greater for bimatoprost (0.45) and beta-blockers (0.47) than for latanoprost (0.27) (p=0.0008). The cost of visits and medications was lowest for beta-blockers ($119.3+/-$78.9) and highest for bimatoprost ($163.8+/-$51.2) (p<0.0001). CONCLUSIONS: Patients were more persistent with latanoprost and demonstrated lower intraocular pressure, fewer visits, and fewer medicine changes when compared to bimatoprost or beta-blocker therapy. In contrast, the beta-blocker group provided lower overall cost.