Safety Evaluation in Iterative Development of Wearable Patches for Aripiprazole Tablets With Sensor: Pooled Analysis of Clinical Trials.

BACKGROUND: Wearable sensors in digital health may pose a risk for skin irritation through the use of wearable patches. Little is known about how patient- and product-related factors impact the risk of skin irritation. Aripiprazole tablets with sensor (AS, Abilify MyCite; Otsuka America Pharmaceutical, Inc) is a digital medicine system indicated for the treatment of patients with schizophrenia, bipolar I disorder, and major depressive disorder. AS includes aripiprazole tablets with an embedded ingestible event marker, a wearable sensor attached to the skin through a wearable patch, a smartphone app, and a web-based portal. To continuously improve the final product, successive iterations of wearable patches were developed, including raisin patch version 4 (RP4), followed by disposable wearable sensor version 5 (DW5), and then reusable wearable sensor version 2 (RW2). OBJECTIVE: This analysis pooled safety data from clinical studies in adult participants using the RP4, DW5, and RW2 wearable patches of AS and evaluated adverse events related to the use of wearable patches. METHODS: Safety data from 12 studies in adults aged 18-65 years from May 2010 to August 2020 were analyzed. All studies evaluated safety, with studies less than 2 weeks also specifically examining human factors associated with the use of the components of AS. Healthy volunteers or patients with schizophrenia, bipolar I disorder, or major depressive disorder were enrolled; those who were exposed to at least 1 wearable patch were included in the safety analysis. Adverse events related to the use of a wearable patch were evaluated. Abrasions, blisters, dermatitis, discoloration, erythema, irritation, pain, pruritus, rash, and skin reactions were grouped as skin irritation events (SIEs). All statistical analyses were descriptive. RESULTS: The analysis included 763 participants (mean [SD] age 42.6 [12.9] years; White: n=359, 47.1%; and male: n=420, 55%). Participants were healthy volunteers (n=269, 35.3%) or patients with schizophrenia (n=402, 52.7%), bipolar I disorder (n=57, 7.5%), or major depressive disorder (n=35, 4.6%). Overall, 13.6% (104/763) of the participants reported at least 1 SIE, all of which were localized to the wearable patch site. Incidence of ≥1 patch-related SIEs was seen in 18.1% (28/155), 14.2% (55/387), and 9.2% (28/306) of participants who used RP4, DW5, and RW2, respectively. Incidence of SIE-related treatment discontinuation was low, which is reported by 1.9% (3/155), 3.1% (12/387), and 1.3% (4/306) of participants who used RP4, DW5, and RW2, respectively. CONCLUSIONS: The incidence rates of SIEs reported as the wearable patch versions evolved from RP4 through RW2 suggest that information derived from reported adverse events may have informed product design and development, which could have improved both tolerability and wearability of successive products. TRIAL REGISTRATION: Clinicaltrials.gov NCT02091882, https://clinicaltrials.gov/study/NCT02091882; Clinicaltrials.gov NCT02404532, https://clinicaltrials.gov/study/NCT02404532; Clinicaltrials.gov NCT02722967, https://clinicaltrials.gov/study/NCT02722967; Clinicaltrials.gov NCT02219009, https://clinicaltrials.gov/study/NCT02219009; Clinicaltrials.gov NCT03568500, https://clinicaltrials.gov/study/NCT03568500; Clinicaltrials.gov NCT03892889, https://clinicaltrials.gov/study/NCT03892889.

How to Become a Mentor and Be Good at It.

Mentoring skills are key assets for academic medicine and allied health faculty. Mentors can influence and help to shape the careers of the next generation of health-care providers. Mentors are not only role models but they can also teach the intricacies of professionalism, ethics, values, and the art of medicine. A mentor can be a teacher, a counselor, or an advocate. Mentors can enhance their own leadership skills, improve self-awareness, and increase professional credibility. This article will review the types of mentoring models, the benefits of mentoring, and the core and critical skills of mentoring.

The Use of Biologics in NFL Athletes: An Expert Consensus of NFL Team Physicians.

Background: There is a lack of published information outlining the use of biologics in National Football League (NFL) athletes and limited data to guide biologic treatment strategies. Purpose: To develop a consensus on the use of biologics among NFL team physicians. Study Design: Consensus statement. Methods: A working group of 6 experts convened a consensus process involving NFL team physicians using validated Delphi methodology. Physicians from 32 NFL teams as well as NFL London were invited to take part. This iterative process was used to define statements on the use of biologics in NFL athletes. A recent scoping review exploring biologics in professional athletes was used to inform the first of 3 rounds of surveys, with statements considered under 7 headings: biologics in general, challenges of treating NFL athletes, terminology/nomenclature, autologous blood products, cell-based therapies, guidance for NFL team physicians, and biologic research in the NFL. In addition to rating agreement, experts were encouraged to propose further items or modifications. Predefined criteria were used to refine item lists after each survey. For a consensus within the final round, defined a priori, items were included in the final information set if a minimum of 75% of respondents agreed and fewer than 10% disagreed. Results: Physicians from 26 NFL teams and NFL London responded to the initial invitation to participate in the Delphi process; 88.9% of participating team physicians completed the round 1 survey, with response rates of 87.5% in round 2 and 95.2% in round 3. After 3 rounds, 47 statements reached a consensus. A consensus was achieved that platelet-rich plasma has a positive impact on patellar tendinopathy and on symptoms in early osteoarthritis but not for other indications. NFL team physicians agreed that while cell therapies have the potential to improve symptoms, the misrepresentation of uncharacterized preparations as "stem cells" has contributed to the widespread use of unproven therapies. Conclusion: This study established an expert consensus on 47 statements relating to the use of biologics in NFL athletes. In addition to providing clinical guidance for the use of biologics in NFL athletes, this study identified key areas for future focus including the development of athlete education materials.

Traumatic rotator cuff tears with concomitant shoulder dislocation: tear characteristics and postsurgical outcomes.

BACKGROUND: Arthroscopic rotator cuff repair has been shown to have favorable outcomes following traumatic rotator cuff tear with concomitant shoulder dislocation. The aim of this study was to compare outcomes and tear characteristics between patients who underwent arthroscopic rotator cuff repair following traumatic tear with shoulder dislocation to those without dislocation. METHODS: A retrospective review of 226 consecutive patients with traumatic rotator cuff tears who underwent arthroscopic repair between 2013 and 2017 with a minimum of 1-year follow-up was performed. Patients with traumatic dislocations and concomitant rotator cuff tears were placed in the Dislocation & Tear cohort (DT cohort) and were matched 1:2 with a second cohort sustaining traumatic cuff tears without dislocation (T cohort). Primary outcomes were injury characteristics including tendon involvement and atrophy and tear size and thickness. Secondary outcomes were postoperative strength and range of motion (ROM) in forward flexion (FF), external rotation (ER), and internal rotation (IR); patient-reported outcomes including Subjective Shoulder Value, visual analog scale, and American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form; complications including repair failure (defined as symptomatic retear confirmed on postoperative magnetic resonance imaging), infection, adhesive capsulitis, and impingement; and rates of revision surgery. RESULTS: There were 18 patients in the DT Cohort and 36 patients in the T Cohort with no significant differences in time to final follow-up (50.4 ± 24.5 months vs. 49.0 ± 30.4 months, P = .73). The DT cohort displayed a larger mean tear size (34 ± 12 mm vs. 19 ± 12 mm, P = .01) and had greater infraspinatus involvement (78% vs. 36%, P = .004) and subscapularis involvement (72% vs. 39%, P = .02) than the T cohort. With regard to strength, postoperative ER strength was less likely to be 5/5 in the DT Cohort (53% vs. 94% of patients with 5/5 strength, P = .002) compared with the T cohort. With regard to ROM, the DT cohort had significantly lower preoperative FF (90° ± 55° vs. 149° ± 33°, P < .001), ER (36 ± 21° vs. 52° ± 14°, P = .02), and IR (5.4 ± 2.1 vs. 7.5 ± 1.2, P = .002) compared with the T cohort but had similar FF, ER, and IR outcomes postoperatively. There were no differences between the groups for complications and postoperative patient-reported outcomes. CONCLUSION: Traumatic rotator cuff tears with concomitant dislocations are associated with larger tear size and greater infraspinatus and subscapularis involvement than traumatic tears without dislocation. Arthroscopic repair of this injury is associated with lower preoperative ROM in FF, ER, and IR, as well as lower postoperative ER strength compared with traumatic tears without dislocation. Nonetheless, excellent patient-reported outcomes can be achieved following arthroscopic repair similar to patients without dislocation.

Brief Strategy Training in Aging: Near Transfer Effects and Mediation of Gains by Improved Self-Regulation.

A common approach to cognitive intervention for adults is memory strategy training, but limited work of this type has examined intervention effects in relation to self-regulation (e.g., strategy usage, memory beliefs) and few have established near transfer (training-related performance gain on untrained tasks related to the target task). The present research, Everyday Memory Clinic-Revised (EMC-R), examined whether relatively brief face-name association training, offering elements focused on self-regulation, can improve name recall, enhance memory self-regulation, and lead to near transfer. Participants were 122 healthy, well-educated middle-aged and older adults (51-90 years old) randomly assigned to a strategy training program (SO), a comparable program with a theoretical self-regulatory boost (SB), or a waitlist control group. Compared to the waitlist group, both groups of trainees demonstrated higher pretest-posttest improvements in name recall (target task), memory self-efficacy, and effective strategy use, as well as the near transfer of gains to nontrained associative tasks, a rare finding in strategy training research. Furthermore, changes in memory self-efficacy and strategy use fully mediated the effect of training on name recall. This innovative approach for brief memory intervention offers a model for successful training that can be easily disseminated via community centers and lifelong learning programs.

The Emerging Role of Telehealth for Concussion Clinical Care During the Coronavirus (COVID-19) Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has substantially altered the delivery of healthcare for providers and their patients. Patients have been reticent to seek care for many diseases and injuries including concussion due to fears of potential exposure to COVID-19. Moreover, because of social distancing recommendations and stay-at-home orders, patient screening, evaluation, and delivery of care have become less efficient or impossible to perform via in-person clinic visits. Consequently, there was a sudden need to shift healthcare delivery from primarily in-person visits to telehealth. This sudden shift in healthcare delivery brings with it both challenges and opportunities for clinical concussion care. This article is designed to discuss these challenges and opportunities and provide an experiential-based framework for providing concussion care via telehealth. We first provide an overview of a clinical concussion model utilized at concussion specialty clinics from 3 geographically disparate healthcare systems for in-person service delivery prior to COVID-19. We then discuss the creation of new clinical workflows to facilitate the continued provision of concussion specialty care using telehealth. Finally, we examine lessons learned during this healthcare delivery shift including limitations and potential barriers for telehealth for concussion care, as well as opportunities for expansion of concussion care in rural and underserved areas. We also discuss the need to empirically evaluate the comparative efficacy of telehealth and in-person concussion care moving forward.

Postoperative Use of Blood Flow Restriction in Orthopedics.

Blood flow restriction (BFR) therapy is being used more frequently for rehabilitation from orthopedic injuries. Several physiologic mechanisms of action, at local and systemic levels, have been proposed. Numerous studies have investigated the effects of BFR training in healthy athletes; however, limited clinical data exist supporting the use of BFR after surgery. Given that BFR training may facilitate muscle development using low-load resistance exercises, it offers a unique advantage for the post-surgical patient who cannot tolerate traditional high resistance training. [Orthopedics. 2021;44(6):e694-e698.].

The Impact of Naturalistic Age Stereotype Activation.

Almost self-fulfilling, commonly held negative stereotypes about old age and memory can impair older adults' episodic memory performance, due to age-based stereotype threat or self-stereotyping effects. Research studies demonstrating detrimental impacts of age stereotypes on memory performance are generally conducted in research laboratories or medical settings, which often underestimate memory abilities of older adults. To better understand the "real world" impact of negative age and memory stereotypes on episodic memory, the present research tested story recall performance of late middle-aged and older adults (N = 51) following a naturalistic age stereotype manipulation, wherein every day, newspaper-style materials (comics and puzzles) were either embedded with negative age and memory stereotype stimuli (stereotype group) or neutral stimuli (control group). Furthermore, all participants were tested in favorable, familiar environments. Potential moderators of the stereotype effects, e.g., metamemory beliefs, were assessed at baseline. Current memory evaluation and subjective age, as well as perceived stereotype threat and task-related anxiety, were assessed following the stereotype manipulation as potential mechanisms of the expected stereotype effects. Results suggested a contrast effect, as the stereotype group demonstrated superior story recall performance compared to the control group. Marginally significant moderation effects by age and perceived stereotype threat indicated that stereotype rejection was present for late middle-aged adults but not older adults, indicative of stereotype lift, and for individuals who reported low and average, but not high, levels of perceived stereotype threat. Additionally, a trend suggested more positive memory evaluation for those in the stereotype group who reported awareness of the stereotype stimuli than those who did not notice the stimuli. These results are consistent with other research demonstrating benefits to memory performance in adulthood based on motivational and contextual factors, such as using relevant memory materials and testing in favorable conditions. Moreover, the results of this study contribute to our understanding of individuals' responses to different types of stereotype stimuli, and the differential impact of stereotype manipulations that are subtle versus blatant. Individuals were motivated to counteract negative stereotype effects when conditions were supportive, stereotype presentations were naturalistic, and personal beliefs were positive.

Anatomic single vs. double-bundle ACL reconstruction: a randomized clinical trial-Part 1: clinical outcomes.

PURPOSE: Compare clinical outcomes of anatomic single-bundle (SB) to anatomic double-bundle (DB) anterior cruciate ligament reconstruction (ACLR). It was hypothesized that anatomic DB ACLR would result in better International Knee Documentation Committee Subjective Knee Form (IKDC-SKF) scores and reduced anterior and rotatory laxity compared to SB ACLR. METHODS: Active individuals between 14 and 50 years of age that presented within 12 months of injury were eligible to participate. Individuals with prior injury or surgery of either knee, greater than a grade 1 concomitant knee ligament injury, or ACL insertion sites less than 14 mm or greater than 18 mm were excluded. Subjects were randomized to undergo SB or DB ACLR with a 10 mm-wide quadriceps tendon autograft harvested with a patellar bone block and were followed for 24 months. The primary outcome measures included the IKDC-SKF and KT-1000 (side to side difference) and pivot shift tests. Other secondary outcomes included measures of sports activity and participation, range of motion (ROM) and re-injury. RESULTS: Enrollment in the study was suspended due to patellar fractures related to harvest of the patellar bone plug. At that time, 57 subjects had been randomized (29 DB) and two-year follow-up was attained from 51 (89.5%). At 24-month follow-up there were no between-group differences detected for the primary outcomes. Twenty-one (77.8%) DB's and 20 (83.3%) SB's reported returning to pre-injury sports 2 years after surgery (n.s) Three subjects (2 DB's, 5.3% of total) sustained a graft rupture and 5 individuals (4 SB's, 8.8% of total) had a subsequent meniscus injury. CONCLUSIONS: Due to the early termination of the study, there were no detectable differences in clinical outcome between anatomic SB and DB ACLR when performed with a quadriceps tendon autograft with a bone block in individuals with ACL insertion sites that range from 14 to 18 mm. LEVEL OF EVIDENCE: Level 2.

Anatomic single- and double-bundle ACL reconstruction both restore dynamic knee function: a randomized clinical trial-part II: knee kinematics.

PURPOSE: Compare side-to-side differences for knee kinematics between anatomic single-bundle (SB) and anatomic double-bundle (DB) ACLR during downhill running at 6 and 24 months post ACLR using high-accuracy dynamic stereo X-ray imaging. It was hypothesized that anatomic DB ACLR would better restore tibio-femoral kinematics compared to SB ACLR, based on comparison to the contralateral, uninjured knee. METHODS: Active individuals between 14 and 50 years of age that presented within 12 months of injury were eligible to participate. Individuals with prior injury or surgery of either knee, greater than a grade 1 concomitant knee ligament injury, or ACL insertion sites less than 14 mm or greater than 18 mm were excluded. Subjects were randomized to undergo SB or DB ACLR with a 10 mm-wide quadriceps tendon autograft harvested with a patellar bone block and were followed for 24 months. Dynamic knee function was assessed during treadmill downhill running using a dynamic stereo X-ray tracking system at 6 and 24 months after surgery. Three-dimensional tibio-femoral kinematics were calculated and compared between limbs (ACLR and uninjured contralateral) at each time point. RESULTS: Fifty-seven subjects were randomized (29 DB) and 2-year follow-up was attained from 51 (89.5%). No significant differences were found between SB and DB anatomic ACLR for any of the primary kinematic variables. CONCLUSIONS: Contrary to the study hypothesis, double-bundle reconstruction did not show superior kinematic outcomes compared to the single-bundle ACLR. While neither procedure fully restored normal knee kinematics, both anatomic reconstructions were similarly effective for restoring near-normal dynamic knee function. The findings of this study indicate both SB and DB techniques can be used for patients with average size ACL insertion sites. LEVEL OF EVIDENCE: Level I.

Rare Variant Double-Layered Lateral Meniscus Detected During Arthroscopy in a Young Gymnast After a Hyperextension Knee Injury: A Case Report.

CASE: A 15-year-old high-level gymnast sustained a hyperextension knee injury and was diagnosed with a lateral meniscus tear on advanced imaging. During arthroscopy, a redundant meniscus was encountered overlying an otherwise normal, intact lateral meniscus, consistent with a double-layer lateral meniscus. The redundant meniscus was resected, and the patient was able to return to gymnastics at her previous high level of competition. CONCLUSIONS: Abnormalities of the lateral meniscus may be poorly characterized or undetected on preoperative imaging studies. When the decision is made to proceed with surgery, a vigilant diagnostic arthroscopic examination can facilitate the detection and treatment of unanticipated pathology.

Own-age bias in face-name associations: Evidence from memory and visual attention in younger and older adults.

Successfully learning and remembering people's names is a challenging memory task for adults of all ages, and this already difficult social skill worsens with age, even in normative "healthy" aging. The own-age bias, a type of in-group bias, could affect the difficulty of this task across age. Past evidence supports an own-age bias in face processing, wherein individuals preferably attend to and better recognize faces of members of their own age group. However, the own-age bias has not been examined previously in relation to explicit face-name associative encoding and subsequent name retrieval, despite the importance of this social skill. Using behavioral and eye-tracking methodology, this cross-sectional research investigated the own-age bias for name memory (recognition and recall) and visual attention (fixation count, looking time, and normalized pupil size) when learning novel face-name pairs. Younger adult (n = 90) and older adult (n = 84) participants completed a face-name association task that tested name memory for younger and older female and male faces, while eye-tracking data were recorded. The visual attention variables taken from the eye-tracking data showed significant age-of-face effects at both encoding and retrieval, but no overall own-age bias in attention. Both younger and older participants showed an own-age bias in name recall with better memory for names paired with faces of their own age, as compared to other-aged faces. This cross-over effect for name memory suggests that memory for information with high social and affective relevance to the individual may be relatively spared in aging, despite overall age-related declines in memory performance.

Patellar Fractures After the Harvest of a Quadriceps Tendon Autograft With a Bone Block: A Case Series.

BACKGROUND: The quadriceps tendon is a versatile graft option, and the clinical implications of a quadriceps tendon harvest need to be further defined. PURPOSE: To review surgical considerations for the safe harvest of a quadriceps tendon autograft for anterior cruciate ligament (ACL) reconstruction, with a focus on the risk of patellar fractures. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A series of 57 patients underwent ACL reconstruction with a quadriceps tendon autograft with a patellar bone block from March 2011 to December 2012 at a single institution. Patients who sustained a patellar fracture were identified. The clinical course for each patient was reviewed with International Knee Documentation Committee (IKDC) subjective knee form scores through 2-year follow-up. RESULTS: The incidence of patellar fractures was 3.5% intraoperatively and 8.8% at 2 years. This included 2 intraoperative fractures, 1 fracture during strength testing, and 2 occult fractures detected on computed tomography (CT) performed 6 months postoperatively for research purposes in asymptomatic participants. For the 5 patients with a patellar fracture with 24-month follow-up, the IKDC scores were 91.95, 91.95, 100.00, 100.00, and 64.37. CONCLUSION: Careful consideration of the quadriceps tendon and patellar anatomy is needed to safely harvest the bone plug from the superior pole of the patella. The consequences of a quadriceps tendon autograft harvest, specifically with regard to the risks associated with fractures of the patella during the harvest, demand full consideration. Postoperative imaging with CT may identify abnormalities in patients who are otherwise asymptomatic.

Age differences in self-set goal effects for memory.

Research has shown that goal setting leads to gains in memory performance and memory self-efficacy across adulthood when goals are set by experimenters and accompanied by positive feedback. However, self-set memory goals have had less consistent impact. This research extended past studies on aging and memory goals to examine the impact of self-set goals using anchors to guide goal selection. Two trials of name, text, and list recall were administered to younger and older adults, comparing goal and no-goal groups. After baseline, participants assigned to the goal group set personal goals for memory gain on a second, post-goal trial for each of the three tasks. Anchoring for goal-setting was used to encourage the selection of realistic, yet challenging goals. Younger and older participants set comparable goals. Only younger adults showed a motivational response (higher gains across trials for goals than no goals), even though older adults reported being just as committed to their personal goals. Older adults may have failed to show reliable goal-related gains because no positive feedback was offered or because they were unable to activate effective strategies for improved performance.

False feedback and beliefs influence name recall in younger and older adults.

Feedback is an important self-regulatory process that affects task effort and subsequent performance. Benefits of positive feedback for list recall have been explored in research on goals and feedback, but the effect of negative feedback on memory has rarely been studied. The current research extends knowledge of memory and feedback effects by investigating face-name association memory and by examining the potential mediation of feedback effects, in younger and older adults, through self-evaluative beliefs. Beliefs were assessed before and after name recognition and name recall testing. Repeated presentation of false positive feedback was compared to false negative feedback and a no feedback condition. Results showed that memory self-efficacy declined over time for participants in the negative and no feedback conditions but was sustained for those receiving positive feedback. Furthermore, participants who received negative feedback felt older after testing than before testing. For name recall, the positive feedback group outperformed the negative feedback and no feedback groups combined, with no age interactions. The observed feedback-related effects on memory were fully mediated by changes in memory self-efficacy. These findings advance our understanding of how beliefs are related to feedback in memory and inform future studies examining the importance of self-regulation in memory.

Interval Throwing and Hitting Programs in Baseball: Biomechanics and Rehabilitation.

Baseball injuries from throwing and hitting generally occur as a consequence of the repetitive and high-energy motions inherent to the sport. Biomechanical studies have contributed to understanding the pathomechanics leading to injury and to the development of rehabilitation programs. Interval-based throwing and hitting programs are designed to return an athlete to competition through a gradual progression of sport-specific exercises. Proper warm-up and strict adherence to the program allows the athlete to return as quickly and safely as possible.