Efficacy and Safety of Transdermal Abaloparatide in Postmenopausal Women with Osteoporosis: A Randomized Study.

Anabolic therapies, recommended for patients at very high fracture risk, are administered subcutaneously (SC). The objective of this study was to evaluate the efficacy and safety of the abaloparatide microstructured transdermal system (abaloparatide-sMTS) as an alternative to the SC formulation. This phase 3, noninferiority study (NCT04064411) randomly assigned postmenopausal women with osteoporosis (N = 511) 1:1 to open-label abaloparatide administered daily via abaloparatide-sMTS or SC injection for 12 months. The primary comparison between treatment groups was the percentage change in lumbar spine bone mineral density (BMD) at 12 months, with a noninferiority margin of 2.0%. Secondary endpoints included percentage change in total hip and femoral neck BMD, bone turnover markers, dermatologic safety, and new clinical fracture incidence. At 12 months, percentage increase from baseline in lumbar spine BMD was 7.14% (SE: 0.46%) for abaloparatide-sMTS and 10.86% (SE: 0.48%) for abaloparatide-SC (treatment difference: -3.72% [95% confidence interval: -5.01%, -2.43%]). Percentage change in total hip BMD was 1.97% for abaloparatide-sMTS and 3.70% for abaloparatide-SC. Median changes from baseline at 12 months in serum procollagen type I N-terminal propeptide (s-PINP) were 52.6% for abaloparatide-sMTS and 74.5% for abaloparatide-SC. Administration site reactions were the most frequently reported adverse events (abaloparatide-sMTS, 94.4%; abaloparatide-SC, 70.5%). Incidence of serious adverse events was similar between groups. Mild or moderate skin reactions occurred with abaloparatide-sMTS with no identifiable risk factors for sensitization reactions. Few new clinical fractures occurred in either group. Noninferiority of abaloparatide-sMTS to abaloparatide-SC for percentage change in spine BMD at 12 months was not demonstrated; however, clinically meaningful increases from baseline in lumbar spine and total hip BMD were observed in both treatment groups. © 2023 Radius Health, Inc and The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Identifying and treating resistant hypertension in PRECISION: A randomized long-term clinical trial with aprocitentan.

The design and baseline data of the PRECISION study, which evaluates the effect of the dual endothelin receptor antagonist aprocitentan on blood pressure (BP) in patients with resistant hypertension (RHT) are presented. The study is a blinded, randomized, parallel-group Phase 3 study and its three-part design assesses the short-term and sustained long-term effects of aprocitentan on BP. Results are expected in 2022. Patients with uncontrolled BP (measured as unattended automated office BP) despite the use of three or more antihypertensive medications for at least 1 year were screened. They were switched to a single-tablet triple fixed combination antihypertensive therapy for at least 4 weeks before entering a single-blind placebo run-in period. The 4-week placebo run-in period further excluded placebo responders. The randomization period consisted of three sequential parts: (1) a 4-week double-blind part with aprocitentan 12.5 mg, 25 mg, or placebo (1:1:1 ratio); (2) a 32-week single-blind part with aprocitentan 25 mg; and (3) a 12-week randomized withdrawal part with aprocitentan 25 mg or placebo (1:1 ratio). The purpose was to demonstrate the BP lowering effect of aprocitentan in RHT (Part 1) and the persistence of this effect (Parts 2 and 3). Out of 1965 screened patients, 730 were randomized resulting in an overall inclusion failure rate of 62.8%. The most common reason for exclusion (44.4% of all screened patients) was failure to meet the BP inclusion criteria. These results underline the high proportion of pseudoresistant hypertension among patients referred for RHT.

Impact of First Eye versus Second Eye Cataract Surgery on Visual Function and Quality of Life.

PURPOSE: To compare the impact of first eye versus second eye cataract surgery on visual function and quality of life. DESIGN: Cohort study. PARTICIPANTS: A total of 328 patients undergoing separate first eye and second eye phacoemulsification cataract surgeries at 5 veterans affairs centers in the United States. Patients with previous ocular surgery, postoperative endophthalmitis, postoperative retinal detachment, reoperation within 30 days, dementia, anxiety disorder, hearing difficulty, or history of drug abuse were excluded. METHODS: Patients received complete preoperative and postoperative ophthalmic examinations for first eye and second eye cataract surgeries. Best-corrected visual acuity (BCVA) was measured 30 to 90 days preoperatively and postoperatively. Patients completed the National Eye Institute Visual Functioning Questionnaire (NEI-VFQ) 30 to 90 days preoperatively and postoperatively. The NEI-VFQ scores were calculated using a traditional subscale scoring algorithm and a Rasch-refined approach producing visual function and socioemotional subscale scores. MAIN OUTCOME MEASURES: Postoperative NEI-VFQ scores and improvement in NEI-VFQ scores comparing first eye versus second eye cataract surgery. RESULTS: Mean age was 70.4 years (±9.6 standard deviation [SD]). Compared with second eyes, first eyes had worse mean preoperative BCVA (0.55 vs. 0.36 logarithm of the minimum angle of resolution (logMAR), P < 0.001), greater mean BCVA improvement after surgery (-0.50 vs. -0.32 logMAR, P < 0.001), and slightly worse postoperative BCVA (0.06 vs. 0.03 logMAR, P = 0.039). Compared with first eye surgery, second eye surgery resulted in higher postoperative NEI-VFQ scores for nearly all traditional subscales (P < 0.001), visual function subscale (-3.85 vs. -2.91 logits, P < 0.001), and socioemotional subscale (-2.63 vs. -2.10 logits, P < 0.001). First eye surgery improved visual function scores more than second eye surgery (-2.99 vs. -2.67 logits, P = 0.021), but both first and second eye surgeries resulted in similar improvements in socioemotional scores (-1.62 vs. -1.51 logits, P = 0.255). CONCLUSIONS: Second eye cataract surgery improves visual function and quality of life well beyond levels achieved after first eye cataract surgery alone. For certain socioemotional aspects of quality of life, second eye cataract surgery results in comparable improvement to first eye cataract surgery.

Outcomes after cataract surgery in eyes with pseudoexfoliation: Results from the Veterans Affairs Ophthalmic Surgery Outcomes Data Project.

OBJECTIVE: To compare clinical outcomes of cataract surgery in eyes with and without pseudoexfoliation (PXF). DESIGN: Retrospective deidentified data analysis. PARTICIPANTS: A total of 123 PXF and 4776 non-PXF eyes of patients who underwent cataract surgery. METHODS: We compared data on visual acuity, Visual Function Questionnaire (VFQ)-based quality of life, and complications in PXF and non-PXF eyes from the Veterans Affairs (VA) Ophthalmic Surgery Outcomes Data Project across 5 VA medical centres. RESULTS: Pupillary expansion devices were used in 31 (25.2%) PXF cases and 398 (8.4%) non-PXF cases (p < 0.0001). Capsular tension rings were used in 6 (4.9%) PXF cases and 55 (1.2%) non-PXF cases (p < 0.004). The following complications occurred more frequently in PXF cases: zonular dehiscence without vitrectomy (4 [3.3%] PXF cases vs 40 [0.8%] non-PXF cases p = 0.02), persistent inflammation (28 [24.1%] vs 668 [14.5%]; p = 0.007), and persistent intraocular pressure elevation (5 [4.3%] vs 68 [1.5%]; p = 0.03). Best corrected visual acuity (BCVA) improved in both groups after 1 month, but 87 (83.7%) PXF cases achieved postoperative BCVA better than or equal to 20/40 compared to 3991 (93.8%) non-PXF cases (p = 0.0003). There was no significant difference in the postoperative composite VFQ scores between PXF (82.1 ± 16.9) and non-PXF cases (84.2 ± 16.8, p = 0.09). CONCLUSIONS: Several complications occurred more frequently in the PXF group compared to the non-PXF group, and fewer PXF cases achieved BCVA better than or equal to 20/40. Despite this, both groups experienced similar improvement in vision-related quality of life after cataract surgery.

American Society of Anesthesiologists classification in cataract surgery: Results from the Ophthalmic Surgery Outcomes Data Project.

PURPOSE: To explore the association of American Society of Anesthesiologists (ASA) classification with cataract surgery outcomes. SETTING: Five Veterans Affairs Medical Centers, United States. DESIGN: Retrospective observational cohort study. METHODS: The study analyzed the outcomes of cataract surgery cases. Corrected distance visual acuity (CDVA), unanticipated events, and vision-related quality of life (VRQL) were assessed using the National Eye Institute Visual Function Questionnaire (NEI-VFQ), comparing ASA classes I through IV. For some analyses, ASA classes I and II were designated as Group A and ASA classes III and IV were designated Group B. RESULTS: Of the 4923 cases, 875 (17.8%) were in Group A, 4032 (81.9%) were in Group B, and 16 (0.3%) had missing data. The mean CDVA and mean composite NEI-VFQ score improved after cataract surgery in both groups (P < .0001); however, Group A had a better mean postoperative CDVA and postoperative VFQ composite scores than Group B (P < .0001, both outcomes). A higher ASA class was associated with an increased risk for 2 unanticipated events; that is, clinically significant macular edema (CSME) (Group A: 4 [0.47%] versus Group B: 50 [1.28%]; adjusted odds ratio [OR], 3.02; 95% confidence interval [CI], 1.02-13.05; P = 0.04) and readmission to the hospital within 30 days (2 [0.23%] versus 56 [1.41%]; OR, 8.26; 95% CI, 1.71-148.62; P = .004) CONCLUSIONS: Among United States veterans, the ASA classification could be an important predictor of VRQL and visual outcomes. In this cohort, it was associated with an increased risk for 2 serious unanticipated events-CSME and readmission to the hospital-both costly, unwanted outcomes. FINANCIAL DISCLOSURE: Dr. Vollman is a consultant to Forsight Vision5. None of the authors has a financial or proprietary interest in any material or method mentioned.

Outcomes of cataract surgery with residents as primary surgeons in the Veterans Affairs Healthcare System.

PURPOSE: To explore visual outcomes, functional visual improvement, and events in resident-operated cataract surgery cases. SETTING: Veterans Affairs Ophthalmic Surgery Outcomes Database Project across 5 Veterans Affairs Medical Centers. DESIGN: Retrospective data analysis of deidentified data. METHODS: Cataract surgery cases with residents as primary surgeons were analyzed for logMAR corrected distance visual acuity (CDVA) and vision-related quality of life (VRQL) measured by the modified National Eye Institute Vision Function Questionnaire and 30 intraoperative and postoperative events. In some analyses, cases without events (Group A) were compared with cases with events (Group B). RESULTS: The study included 4221 cataract surgery cases. Preoperative to postoperative CDVA improved significantly in both groups (P < .0001), although the level of improvement was less in Group B (P = .03). A CDVA of 20/40 or better was achieved in 96.64% in Group A and 88.25% in Group B (P < .0001); however, Group B had a higher prevalence of preoperative ocular comorbidities (P < .0001). Cases with 1 or more events were associated with a higher likelihood of a postoperative CDVA worse than 20/40 (odds ratio, 3.82; 95% confidence interval, 2.92-5.05; P < .0001) than those who did not experience an event. Both groups had a significant increase in VRQL from preoperative levels (both P < .0001); however, the level of preoperative to postoperative VRQL improvement was significantly less in Group B (P < .0001). CONCLUSION: Resident-operated cases with and without events had an overall significant improvement in visual acuity and visual function compared with preoperatively, although this improvement was less marked in those that had an event. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned.

Cataract Surgery Outcomes in Glaucomatous Eyes: Results From the Veterans Affairs Ophthalmic Surgery Outcomes Data Project.

PURPOSE: To compare visual acuity outcomes, vision-related quality of life, and complications related to cataract surgery in eyes with and without glaucoma. DESIGN: Retrospective cohort study. METHODS: Cataract surgery outcomes in cases with and without glaucoma from the Veterans Affairs Ophthalmic Surgical Outcomes Data Project were compared. RESULTS: We identified 608 glaucoma cases and 4306 controls undergoing planned cataract surgery alone. After adjusting for age, pseudoexfoliation, small pupil, prior ocular surgery, and anterior chamber depth, we found that glaucoma cases were more likely to have posterior capsular tear with vitrectomy (odds ratio [OR] 1.8, P = .03) and sulcus intraocular lens placement (OR 1.65, P = .03) during cataract surgery. Glaucoma cases were more likely to have postoperative inflammation (OR 1.73, P < .0001), prolonged elevated intraocular pressure (OR 2.96, P = .0003), and additional surgery within 30 days (OR 1.92, P = .03). Mean best-corrected visual acuity (BCVA) and Visual Function Questionnaire (VFQ) scores significantly improved after cataract surgery in both groups (P < .0001), but there were larger improvements in BCVA (P = .01) and VFQ composite scores (P < .0001) in the nonglaucoma vs the glaucoma group. A total of 3621 nonglaucoma cases (94.1%) had postoperative BCVA 20/40 or better, compared to 466 glaucoma cases (89.6%) (P = .0003). CONCLUSIONS: Eyes with glaucoma are at increased risk for complications and have more modest visual outcomes after cataract surgery compared to eyes without glaucoma. Despite this, glaucoma patients still experience significant improvement in vision-related outcomes after cataract extraction. Further study is needed to explore potential factors that influence cataract surgery outcomes in glaucomatous eyes.

Functional Visual Improvement After Cataract Surgery in Eyes With Age-Related Macular Degeneration: Results of the Ophthalmic Surgical Outcomes Data Project.

PURPOSE: To determine if cataract surgery on eyes with AMD confers as much functional visual improvement as surgery on eyes without retinal pathology. METHODS: This is a retrospective analysis of 4924 cataract surgeries from the Veterans Healthcare Administration Ophthalmic Surgical Outcomes Data Project (OSOD). We included cases of eyes with AMD that had both preoperative and postoperative NEI-VFQ-25 questionnaires submitted and compared their outcomes with controls without retinal pathology. We excluded patients with other retinal pathologies (740 patients). The analyses compared changes in visual acuity and overall functional visual improvement and its subscales using t-tests, multivariate logistic regressions, and linear regression modeling. RESULTS: Preoperative and postoperative questionnaires were submitted by 58.3% of AMD and 63.8% of no retinal pathology cases (controls). Analysis of overall score showed that cataract surgery on eyes with AMD led to increased visual function (13.8 ± 2.4 NEI-VFQ units, P < 0.0001); however, increases were significantly less when compared with controls (-6.4 ± 2.9 NEI-VFQ units, P < 0.0001). Preoperative best-corrected visual acuity (preBCVA) in AMD was predictive of postoperative visual function (r = -0.38, P < 0.0001). In controls, postoperative visual function was only weakly associated with preBCVA (r = -0.075, P = 0.0002). Patients with AMD with vision of 20/40 or better had overall outcomes similar to controls (-2.2 ± 4.7 NEI-VFQ units, P = 0.37). CONCLUSIONS: Cataract surgery on eyes with AMD offers an increase in functional visual improvement; however, the amount of benefit is associated with the eye's preBCVA. For eyes with preBCVA of 20/40 or greater, the improvement is similar to that of patients without retinal pathology. However, if preBCVA is less than 20/40, the amount of improvement was shown to be significantly less and decreased with decreasing preBCVA.

Ocular blast injuries in mass-casualty incidents: the marathon bombing in Boston, Massachusetts, and the fertilizer plant explosion in West, Texas.

PURPOSE: To report the ocular injuries sustained by survivors of the April 15, 2013, Boston Marathon bombing and the April 17, 2013, fertilizer plant explosion in West, Texas. DESIGN: Multicenter, cross-sectional, retrospective, comparative case series. PARTICIPANTS: Seventy-two eyes of 36 patients treated at 12 institutions were included in the study. METHODS: Ocular and systemic trauma data were collected from medical records. MAIN OUTCOME MEASURES: Types and severity of ocular and systemic trauma and associations with mechanisms of injury. RESULTS: In the Boston cohort, 164 of 264 casualties were transported to level 1 trauma centers, and 22 (13.4%) required ophthalmology consultations. In the West cohort, 218 of 263 total casualties were transported to participating centers, of which 14 (6.4%) required ophthalmology consultations. Boston had significantly shorter mean distances to treating facilities (1.6 miles vs. 53.6 miles; P = 0.004). Overall, rigid eye shields were more likely not to have been provided than to have been provided on the scene (P<0.001). Isolated upper body and facial wounds were more common in West largely because of shattered windows (75.0% vs. 13.6%; P = 0.001), resulting in more open-globe injuries (42.9% vs. 4.5%; P = 0.008). Patients in Boston sustained more lower extremity injuries because of the ground-level bomb. Overall, 27.8% of consultations were called from emergency rooms, whereas the rest occurred afterward. Challenges in logistics and communications were identified. CONCLUSIONS: Ocular injuries are common and potentially blinding in mass-casualty incidents. Systemic and ocular polytrauma is the rule in terrorism, whereas isolated ocular injuries are more common in other calamities. Key lessons learned included educating the public to stay away from windows during disasters, promoting use of rigid eye shields by first responders, the importance of reliable communications, deepening the ophthalmology call algorithm, the significance of visual incapacitation resulting from loss of spectacles, improving the rate of early detection of ocular injuries in emergency departments, and integrating ophthalmology services into trauma teams as well as maintaining a voice in hospital-wide and community-based disaster planning.

Intraoperative floppy iris and prevalence of intraoperative complications: results from ophthalmic surgery outcomes database.

PURPOSE: To estimate the prevalence of untoward events during cataract surgery with the use of pupillary expansion devices and intraoperative floppy iris (IFIS). DESIGN: Retrospective analysis of 4923 cataract surgery cases from the Veterans Affairs Ophthalmic Surgical Outcomes Data Project. METHODS: Outcomes from 5 Veterans Affairs medical centers were analyzed, including use of alpha-blockers (both selective and nonselective), IFIS, intraoperative iris trauma, intraoperative iris prolapse, posterior capsular tear, anterior capsule tear, intraoperative vitreous prolapse, and use of pupillary expansion devices. P values were calculated using the χ(2) test. RESULTS: A total of 1254 patients (25.5%) took alpha-blockers preoperatively (selective, 587; nonselective, 627; both, 40). Of these 1254 patients, 428 patients (34.1%) had documented IFIS. However, 75.2% of patients with IFIS (428/569) had taken alpha-blockers preoperatively (P < .00001). A total of 430 patients (8.7%) had a pupillary expansion device used during their cataract surgery, of which 186 patients (43.4%) had IFIS (P < .0001). Eighty-six patients with IFIS had at least 1 intraoperative complication and 39 patients with IFIS had more than 1 intraoperative complication (P < .001). CONCLUSIONS: The use of either selective or nonselective alpha-antagonists preoperatively demonstrated a significant risk of IFIS. Nonselective alpha-antagonists caused IFIS at a higher prevalence than previously reported. This study did demonstrate statistically significant increased odds of surgical complications in patients with IFIS vs those without IFIS in all groups (those taking selective and nonselective alpha-antagonists and also those not taking medications).

Implementing a one-on-one peer support program for cancer survivors using a motivational interviewing approach: results and lessons learned.

Peer Connect matches cancer survivors and caregivers (guides) with those currently experiencing cancer-related issues seeking support (partners). Motivational interviewing (MI)-based communication skills are taught to provide patient-centered support. There is little guidance about MI-based applications with cancer survivors who may have multiple coping needs. This paper addresses the results and lessons learned from implementing Peer Connect. Thirteen cancer survivors and two caregivers received a 2-day MI, DVD-based training along with six supplemental sessions. Nineteen partners were matched with guides and received telephone support. Evaluation included guide skill assessment (Motivational Interviewing Treatment Integrity Code) and 6-month follow-up surveys with guides and partners. Guides demonstrated MI proficiency and perceived their training as effective. Guides provided on average of five calls to each partner. Conversation topics included cancer fears, family support needs, coping and care issues, and cancer-related decisions. Partners reported that guides provided a listening ear, were supportive, and nonjudgmental. Limited time availability of some guides was a challenge. MI can provide support for cancer survivors and caregivers without specific behavioral concerns (e.g., weight and smoking). An MI support model was both feasible and effective and can provide additional support outside of the medical system.

Telehealth practice recommendations for diabetic retinopathy, second edition.

Ocular telemedicine and telehealth have the potential to decrease vision loss from DR. Planning, execution, and follow-up are key factors for success. Telemedicine is complex, requiring the services of expert teams working collaboratively to provide care matching the quality of conventional clinical settings. Improving access and outcomes, however, makes telemedicine a valuable tool for our diabetic patients. Programs that focus on patient needs, consider available resources, define clear goals, promote informed expectations, appropriately train personnel, and adhere to regulatory and statutory requirements have the highest chance of achieving success.

Outcome of angle surgery in children with aphakic glaucoma.

PURPOSE: To investigate the outcome of trabeculotomy and/or goniotomy for pediatric aphakic glaucoma. METHODS: Retrospective chart review of consecutive children who had congenital cataract surgery between 1990 and 2006 and required goniotomy and/or trabeculotomy for aphakic glaucoma. Treatment success was defined as postoperative intraocular pressure of

Safety and efficacy of AIR inhaled insulin compared with subcutaneous insulin in patients having diabetes and asthma: A 12-month, randomized, noninferiority trial.

BACKGROUND: Long-term safety and efficacy of AIR((R)) inhaled insulin (Eli Lilly and Co., Indianapolis, IN) (AIR is a registered trademark of Alkermes, Inc., Cambridge, MA) in patients with diabetes and concomitant lung disease remain to be established. METHODS: This 1-year, randomized, open-label, active comparator, two-arm, parallel study compared the safety and efficacy of AIR insulin to subcutaneous (SC) insulin in patients having type 1 or type 2 diabetes and asthma. Patients with type 2 diabetes continued taking their prestudy oral antihyperglycemic medication. RESULTS: Change in hemoglobin A1C from baseline to end point was similar for the AIR insulin and SC insulin groups (-0.063 +/- 0.128% and -0.315 +/- 0.128% respectively, P = 0.105), but noninferiority failed to be achieved (the upper limit of the 95% confidence interval [-0.053, 0.555] was >0.4%). The total daily prandial dose increased more in the AIR insulin group than in the SC insulin group (0.150 U/kg and 0.044 U/kg, respectively, P = 0.002). Safety profiles were generally comparable between treatments. At end point, forced expiratory volume in 1 s (FEV(1))/forced vital capacity (FVC) postbronchodilator (-0.016 +/- 0.005 vs. 0.002 +/- 0.005, P = 0.006) and diffusing capacity of the lung for carbon monoxide (-1.214 +/- 0.325 mL/min/torr vs. -0.383 +/- 0.311 mL/min/torr, P = 0.028) both decreased more in the AIR insulin group than in the SC insulin group, but the differences were not present at follow-up. FEV(1) and FVC were similar between treatment groups at end point. Incidences of hypoglycemia were comparable between groups. Insulin antibody binding increased more in the AIR insulin group. Cough was the most common adverse event; however, there was no difference in incidence between the AIR insulin (15.3%) and SC insulin (12.4%) treatment groups (P = 0.572). CONCLUSIONS: In patients who have diabetes and asthma, AIR insulin demonstrated glycemic efficacy similar to SC insulin. Additionally, the safety profile of AIR insulin in patients with and without asthma is consistent.

An outbreak of postoperative gram-negative bacterial endophthalmitis associated with contaminated trypan blue ophthalmic solution.

We report 6 cases of postsurgical endophthalmitis due to gram-negative bacteria associated with contaminated trypan blue dye from a compounding pharmacy. Unopened trypan blue syringes yielded Pseudomonas aeruginosa and Burkholderia cepacia complex on culture, with pulsed-field gel electrophoresis patterns indistinguishable from patient isolates. Contamination of compounded medications should be considered when investigating outbreaks of postoperative endophthalmitis.