Associations between habitual sleep characteristics and cardiometabolic disease risk in corporate executives.

OBJECTIVES: Corporate executive job demands may lead to poor sleep habits, increasing their risk for cardiometabolic disease. This study aimed to describe and explore associations between objectively measured habitual sleep characteristics and cardiometabolic disease risk of corporate executives, while accounting for occupational, psychological, and lifestyle factors. METHODS: Habitual sleep was measured using wrist-worn actigraphy and a sleep diary over seven consecutive days in 61 (68.3% men) corporate executives aged 46.4 ± 8.7years. A composite cardiometabolic disease risk score was determined using body mass index, waist circumference, blood pressure and fasting glucose and lipid concentrations. Prediction models were built using a backward stepwise selection approach to explore associations between sleep characteristics and cardiometabolic disease risk factors adjusting for occupational, psychological, and lifestyle covariates. RESULTS: Average total sleep time was 6.60 ± 0.75 hours, with 51.7% of participants reporting poor sleep quality and 26.2% extending their weekend sleep. Adjusted models showed that lower sleep efficiency (ß = -0.25, 95%CI: -0.43; -0.08, P = .006), shorter weekday total sleep time (ß = -1.37, 95% CI: -2.41, -0.32; P = .011) and catch-up sleep (ß = 0.84, 95%CI: 0.08, 1.60, P = .002) were associated with higher cardiometabolic disease risk scores. Adjusted models also found that shorter average time-in-bed (ß=-2.00, 95%CI: -3.76; -0.18, P = .031), average total sleep time (ß=1.98, 95%CI: -3.70; -0.25, P = .025) and weekday total sleep time (ß = -2.13, 95%CI: -3.56; -0.69, P = .025) as well as catch-up sleep (ß = 1.67, 95% CI: 0.52; 2.83; P = .012) were all associated with a higher body mass index. CONCLUSION: Corporate executives who compromise sleep duration during the working week may increase their risk for obesity and future cardiometabolic disease.

Sustained Cognitive Improvement in Alzheimer's Disease Patients Following a Precision Medicine Protocol: Case Series.

Arguably, the most important parameter in treating cognitive decline associated with Alzheimer's disease is the length of time in which improvement, if achieved at all, is sustained. However, monotherapies such as donepezil and memantine are associated with a more rapid decline than no treatment in patients over multi-year follow-ups. Furthermore, anti-amyloid antibody treatment, which at best simply slows decline, is associated with accelerated cerebral atrophy, resulting in earlier dementia-associated brain volumes for those treated at the MCI stage than untreated patients. In contrast, a precision medicine approach, in which the multiple potential drivers of cognitive decline are identified for each patient and then targeted with a personalized protocol (such as ReCODE), has led to documented improvements in patients with cognitive decline, but long-term follow-up (>5 years) has not been reported previously. Therefore, here, we report sustained cognitive improvement, in some cases for over a decade, in patients treated with a precision medicine protocol-something that has not been reported in patients treated with anti-cholinesterase, glutamate receptor inhibitory, anti-amyloid, or other therapeutic methods. These case studies warrant long-term cohort studies to determine how frequently such sustained cognitive improvements occur in patients treated with precision medicine protocols.

Legal Implications of Psychiatric Assessment for Medical Aid in Dying.

In recent years, several jurisdictions have passed legislation to permit medical aid in dying (MAID) worldwide, with considerable expansion in the availability of this practice. MAID has been defined as the practice of a clinician prescribing lethal drugs in response to a direct request from the patient, with a shared understanding that the patient intends to use the medication to bring about the patient's death. Wider legalization of MAID has prompted debates and legal controversies regarding the extent to which MAID should be available and its application for people experiencing mental illness as the primary indication. This article examines shifting attitudes of professional medical organizations toward MAID. We discuss the existing statutory provisions for psychiatric assessment for MAID in the United States and the implications on such assessments should MAID be expanded to include mental illness as the primary indication. This article also assesses legal disputes concerning MAID regulations and explores the role of psychiatric experts in the practice of MAID.

Advanced Care Planning in Chronic Kidney Disease: Qualitative Impact of the MY WAY Intervention.

CONTEXT: Despite recommendations for shared decision-making and advanced care planning (ACP) for people with chronic kidney disease (CKD), such conversations are infrequent. The MY WAY educational and patient coaching intervention aimed to promote high-quality ACP. OBJECTIVES: This qualitative substudy sought to gain participant feedback on the MY WAY ACP coaching intervention, and how it impacted their wishes, perceptions of kidney care, and factors that helped them reflect on ACP. METHODS: We conducted semi-structured interviews with participants from the intervention arm of the MY WAY study about their prior experience with ACPs in the context of CKD, impressions of the MY WAY intervention, and outcomes of the MY WAY intervention. We conducted a qualitative thematic analysis of transcribed interviews. RESULTS: Among 15 intervention participants, the following major themes emerged: 1) Patients with CKD approach ACP with varied experiences; 2) Patients felt the MY WAY coaching intervention supported ACP by reinforcing values; and 3) Patients found the coaching intervention focused on end of life, but not necessarily on decision making regarding CKD. CONCLUSION: Participants perceived the coaching intervention to have high utility in facilitating ACP, but had a limited impact on CKD-specific decision-making. These findings suggest that the coach plays a crucial role in comfort with ACP conversations and that ACP readiness and engagement may not correlate with treatment preferences or understanding of CKD treatment decisions.

Spatiotemporal changes in imaging features associated with diffuse idiopathic skeletal hyperostosis (DISH).

OBJECTIVES: The purpose of our study was to characterise spatiotemporal features of disease progression in people with diffuse idiopathic skeletal hyperostosis (DISH), early-phase DISH, and those not meeting either criterion who had repeated CT scans of the thoracic spine. METHODS: A retrospective study was designed in collaboration with the Rochester Epidemiology Project to evaluate completeness of ectopic bridging across the thoracic spine and corresponding disease status over an average of 2.7 years (range from 0.2 to 15.0 years) in a cohort of 83 female and 74 male individuals. RESULTS: Over 15% of individuals displayed changes in imaging features over time that resulted in a revised diagnosis along the continuum of DISH. Early-phase DISH was marked by new involvement of previously unaffected motion segments, estimated to occur over 2.1 years. Advanced presentations of DISH were marked by increased prevalence of complete bridging (average two of three available motion segments), estimated to occur over 2.6-2.9 years. Localised nodules of ectopic mineralisation external to and within the intervertebral disc were regularly observed in early-phase DISH. CONCLUSIONS: This is the first characterisation of spatiotemporal features across all phases of DISH, indicating that progression of DISH is characterised by distinct features at different phases along the disease continuum. Localised nodules of mineralisation in the spinal ligaments and within the intervertebral discs coincident with early phases of the disease may be a key factor in the pathogenesis of DISH.

The Forensic Mental Health Implications of Social Media Challenges.

Children and adults are increasingly spending time on social networking sites where they may be exposed to social media challenges. These challenges, which are essentially dares or competitions, often involve participants recording themselves performing various activities to create a short video which they then share online. Many social media challenges may be considered relatively benign, but others may involve behaviors or tasks that lead to adverse outcomes, including injury and death. In this article, the authors describe different types of social media challenges, susceptibility to risk-taking among social media users, and the potential criminal and civil legal aspects of these challenges. This article focuses on the forensic mental health implications of social media challenges, including considerations for forensic psychiatrists and other mental health professionals who may become involved in court cases related to these challenges.

Silhouette showcards confirm altered obesity-associated body image perception in international cohort study of African-origin populations.

OBJECTIVES: Given the increasing prevalence of obesity and need for effective interventions, there is a growing interest in understanding how an individual's body image can inform obesity prevention and management. This study's objective was to examine the use of silhouette showcards to measure body size perception compared with measured body mass index, and assess body size dissatisfaction, in three different African-origin populations spanning the epidemiological transition. An ancillary objective was to investigate associations between body size perception and dissatisfaction with diabetes and hypertension. SETTING: Research visits were completed in local research clinics in respective countries. PARTICIPANTS: Seven hundred and fifty-one African-origin participants from the USA and the Republic of Seychelles (both high-income countries), and Ghana (low/middle-income country). PRIMARY AND SECONDARY OUTCOME MEASURES: Silhouette showcards were used to measure perceived body size and body size dissatisfaction. Objectively measured body size was measured using a scale and stadiometer. Diabetes was defined as fasting blood glucose ≥126 mg/dL and hypertension was defined as ≥130 mm Hg/80 mm Hg. RESULTS: Most women and men from the USA and Seychelles had 'Perceived minus Actual weight status Discrepancy' scores less than 0, meaning they underestimated their actual body size. Similarly, most overweight or obese men and women also underestimated their body size, while normal weight men and women were accurately able to estimate their body size. Finally, participants with diabetes were able to accurately estimate their body size and similarly desired a smaller body size. CONCLUSIONS: This study highlights that overweight and obese women and men from countries spanning the epidemiological transition were unable to accurately perceive their actual body size. Understanding people's perception of their body size is critical to implementing successful obesity prevention programmes across the epidemiological transition.

Associations between fears related to safety during sleep and self-reported sleep in men and women living in a low-socioeconomic status setting.

South Africans living in low socioeconomic areas have self-reported unusually long sleep durations (approximately 9-10 h). One hypothesis is that these long durations may be a compensatory response to poor sleep quality as a result of stressful environments. This study aimed to investigate whether fear of not being safe during sleep is associated with markers of sleep quality or duration in men and women. South Africans (n = 411, 25-50 y, 57% women) of African-origin living in an urban township, characterised by high crime and poverty rates, participated in this study. Participants are part of a larger longitudinal cohort study: Modelling the Epidemiologic Transition Study (METS)-Microbiome. Customised questions were used to assess the presence or absence of fears related to feeling safe during sleep, and the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index were used to assess daytime sleepiness, sleep quality and insomnia symptom severity respectively. Adjusted logistic regression models indicated that participants who reported fears related to safety during sleep were more likely to report poor sleep quality (PSQI > 5) compared to participants not reporting such fears and that this relationship was stronger among men than women. This is one of the first studies outside American or European populations to suggest that poor quality sleep is associated with fear of personal safety in low-SES South African adults.

Comparison of two processing techniques on the sperm quality of semen contaminated with urine.

Urospermia in stallions can occur intermittently, consistently, or as an isolated event, and may result in reduced sperm quality which is often assumed to reduce fertility. Although sperm quality declines in urospermic ejaculates, fertility has not been assessed in mares bred with urine contaminated semen. The aims of this study were to compare sperm quality after simple dilution (SD), cushioned centrifugation (CC) alone, or cushioned centrifugation combined with a 40 % silane-coated silica solution (SC) in semen contaminated with 0, 20, or 40 % (v/v) urine. Sperm quality values tended to decrease as the percent urine increased within all treatments (SD, CC, SC) after 24 h of cooled storage. However, SC treated groups had higher sperm quality compared to SD and CC when exposed to 20 or 40 % (v/v) urine. Differences in pregnancy rates among treatment groups (SD with 0 or 40 % (v/v) urine, or 40 % (v/v) urine followed by SC) were unable to be detected.

Prevalence of diffuse idiopathic skeletal hyperostosis (DISH) and early-phase DISH across the lifespan of an American population.

OBJECTIVES: DISH is a common musculoskeletal disorder; however, the imaging features and disease continuum from early to advanced stages is poorly understood. The purpose of this study was to evaluate the prevalence of DISH and early-phase DISH in an American population and to assess the extent and pattern of ectopic mineralization across the thoracic spine. METHODS: Data were retrieved in collaboration with the Rochester Epidemiology Project. We conducted a retrospective image evaluation of a sample of individuals over 19 years of age with CT of the thoracic spine from a Northern US catchment area. Stratified random sampling by age and sex was used to populate the study. We examined the prevalence and extent of ectopic mineralization along the thoracic spine using previously established criteria. RESULTS: A total of 1536 unique images (766 female and 770 male individuals) including 16 710 motion segments were evaluated for imaging features of the continuum of DISH. Collectively, 40.5% of all motion segments evaluated displayed evidence of ectopic mineralization in the thoracic spine. The prevalence of early-phase DISH was 13.2% (10.4% of female and 15.8% of male individuals). The prevalence of established DISH was 14.2% (7.4% of female and 20.9% of male individuals). Remarkable heterogeneity was detected in individuals within each disease classification, based on the extent of the thoracic spine affected and degree of mineralization. CONCLUSIONS: The continuum of imaging features associated with DISH is detected in more than one in four adults and both sexes in an American population.

Effect of bimatoprost sustained-release intracameral implant on intraocular pressure and medication burden in patients with prior glaucoma surgery.

The present retrospective study evaluated intraocular pressure (IOP) and medication burden after bimatoprost sustained-release (bimatoprost SR, Durysta, Allergan) implantation in patients with glaucoma. A secondary objective was to examine an effect of bimatoprost SR in a subset of patients with prior minimally invasive and incisional glaucoma surgery. A retrospective chart review of 122 eyes that received bimatoprost SR by 6 glaucoma specialists at Wills Eye Hospital between March 2020 and September 2021 was performed. One hundred and eighteen eyes from 84 patients had a reduction in IOP (18.5±5.7mmHg vs. 16.0±5.4mmHg, P<0.01) and required fewer glaucoma medications (2.1±1.4 vs. 1.2±1.2, P<0.01) after bimatoprost SR implantation. In 41 eyes from 31 patients who previously underwent glaucoma surgery (including iStent, goniotomy, trabeculectomy, Xen Gel Stent, or tube shunt surgery), medication burden was decreased after bimatoprost SR implantation (1.9±1.3 vs. 1.0±1.0, P<0.001). These data suggest that bimatoprost SR is an efficacious treatment modality for glaucoma, even in post-surgical patients.

Barriers and Facilitators to Participation and Key Components of Sleep Health Programs: Perspectives for the Corporate Work Environment.

OBJECTIVE: The aim of the study is to explore the barriers and facilitators of participation and key components for sleep health programs designed for corporate work environments. METHODS: Semistructured interviews with corporate executives and occupational medicine specialists in the decision making and management of workplace health promotion programs (WHPP) within their companies were held before and during COVID-19. Interviews were transcribed verbatim and analyzed using thematic content analysis to identify themes. RESULTS: Barrier and facilitator themes emerging from the data include sleep health awareness, work culture, work-family balance, and confidentiality. Key components for sleep health programs included the following: identifying the need for a program, incorporating sleep health risk screening to WHPP, and promoting sleep health by raising awareness thereof. CONCLUSIONS: The identified barriers and facilitators to employee participation and key components of an ideal sleep health program provide guidance for further WHPP.

Echocardiographic Outcomes With Transcatheter Edge-to-Edge Repair for Degenerative Mitral Regurgitation in Prohibitive Surgical Risk Patients.

BACKGROUND: The CLASP IID randomized trial (Edwards PASCAL TrAnScatheter Valve RePair System Pivotal Clinical Trial) demonstrated the safety and effectiveness of the PASCAL system for mitral transcatheter edge-to-edge repair (M-TEER) in patients at prohibitive surgical risk with significant symptomatic degenerative mitral regurgitation (DMR). OBJECTIVES: This study describes the echocardiographic methods and outcomes from the CLASP IID trial and analyzes baseline variables associated with residual mitral regurgitation (MR) ≤1+. METHODS: An independent echocardiographic core laboratory assessed echocardiographic parameters based on American Society of Echocardiography guidelines focusing on MR mechanism, severity, and feasibility of M-TEER. Factors associated with residual MR ≤1+ were identified using logistic regression. RESULTS: In 180 randomized patients, baseline echocardiographic parameters were well matched between the PASCAL (n = 117) and MitraClip (n = 63) groups, with flail leaflets present in 79.2% of patients. Baseline MR was 4+ in 76.4% and 3+ in 23.6% of patients. All patients achieved MR ≤2+ at discharge. The proportion of patients with MR ≤1+ was similar in both groups at discharge but diverged at 6 months, favoring PASCAL (83.7% vs 71.2%). Overall, patients with a smaller flail gap were significantly more likely to achieve MR ≤1+ at discharge (adjusted OR: 0.70; 95% CI: 0.50-0.99). Patients treated with PASCAL and those with a smaller flail gap were significantly more likely to sustain MR ≤1+ to 6 months (adjusted OR: 2.72 and 0.76; 95% CI: 1.08-6.89 and 0.60-0.98, respectively). CONCLUSIONS: The study used DMR-specific echocardiographic methodology for M-TEER reflecting current guidelines and advances in 3-dimensional echocardiography. Treatment with PASCAL and a smaller flail gap were significant factors in sustaining MR ≤1+ to 6 months. Results demonstrate that MR ≤1+ is an achievable benchmark for successful M-TEER. (Edwards PASCAL TrAnScatheter Valve RePair System Pivotal Clinical Trial [CLASP IID]; NCT03706833).

"Diving in the deep-end and swimming": a mixed methods study using normalization process theory to evaluate a learning collaborative approach for the implementation of palliative care practices in hemodialysis centers.

BACKGROUND: Normalization Process Theory (NPT) is an implementation theory that can be used to explain how and why implementation strategies work or not in particular circumstances. We used it to understand the mechanisms that lead to the adoption and routinization of palliative care within hemodialysis centers. METHODS: We employed a longitudinal, mixed methods approach to comprehensively evaluate the implementation of palliative care practices among ten hemodialysis centers participating in an Institute for Healthcare Improvement Breakthrough- Series learning collaborative. Qualitative methods included longitudinal observations of collaborative activities, and interviews with implementers at the end of the study. We used an inductive and deductive approach to thematic analysis informed by NPT constructs (coherence, cognitive participation, collective action, reflexive monitoring) and implementation outcomes. The NoMAD survey, which measures NPT constructs, was completed by implementers at each hemodialysis center during early and late implementation. RESULTS: The four mechanisms posited in NPT had a dynamic and layered relationship during the implementation process. Collaborative participants participated because they believed in the value and legitimacy of palliative care for patients receiving hemodialysis and thus had high levels of cognitive participation at the start. Didactic Learning Sessions were important for building practice coherence, and sense-making was solidified through testing new skills in practice and first-hand observation during coaching visits by an expert. Collective action was hampered by limited time among team members and practical issues such as arranging meetings with patients. Reflexive monitoring of the positive benefit to patient and family experiences was key in shifting mindsets from disease-centric towards a patient-centered model of care. NoMAD survey scores showed modest improvement over time, with collective action having the lowest scores. CONCLUSIONS: NPT was a useful framework for understanding the implementation of palliative care practices within hemodialysis centers. We found a nonlinear relationship among the mechanisms which is reflected in our model of implementation of palliative care practices through a learning collaborative. These findings suggest that the implementation of complex practices such as palliative care may be more successful through iterative learning and practice opportunities as the mechanisms for change are layered and mutually reinforcing. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04125537 . Registered 14 October 2019 - Retrospectively registered.

Prevalence of obesity, hypertension and diabetes among people living with HIV in South Africa: a systematic review and meta-analysis.

BACKGROUND: HIV has become a manageable chronic condition due to the success and scale-up of antiretroviral therapy (ART). Globally, South Africa has the highest number of people living with HIV (PLHIV) and research evidence indicates that countries with the highest burden of PLHIV have a substantial burden of obesity, hypertension (HPT) and type 2 diabetes (T2D). We sought to summarize the burden of these three common NCDs among PLHIV in South Africa. METHODS: In this systematic review, multiple databases were searched for articles reporting on the prevalence of obesity, HPT, and T2D among PLHIV in South Africa published since journal inception until March 2022. A meta-analysis was conducted using random-effects models to obtain pooled prevalence estimates of the three NCDs. Heterogeneity was assessed using X2 test on Cochran's Q statistic. RESULTS: We included 32 studies, with 19, 22 and 18 studies reporting the prevalence of obesity, HPT, and T2D among PLHIV, respectively. The overall prevalence of obesity, HPT, and T2D was 23.2% [95% CI 17.6; 29.9], 25.5% [95% CI 15.6; 38.7], and 6.1% [95% CI 3.8; 9.7] respectively. The prevalence of obesity was significantly higher among women (P = 0.034) compared to men, however the prevalence of HPT and T2D did not differ by sex. The prevalence of each of the three NCDs did not differ significantly between rural, urban, and peri-urban areas. The prevalence of obesity and T2D was higher in studies conducted between 2013 and 2022 compared to studies conducted between 2000 and 2012, while the prevalence of HPT was higher between 2000 and 2012 compared to between 2013 and 2022. CONCLUSIONS: These findings suggest that South Africa is experiencing a syndemic of NCDs among people PLHIV highlighting the need to increase cost-effective interventions and management strategies that involve integrated HIV and NCD care in the South African setting.

Longitudinal White and Gray Matter Response to Precision Medicine-Guided Intervention for Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is a debilitating condition that is widely known to adversely affect gray matter (GM) and white matter (WM) tracts within the brain. Recently, precision medicine has shown promise in alleviating the clinical and gross morphological trajectories of patients with AD. However, regional morphological changes have not yet been adequately characterized. OBJECTIVE: Investigate regional morphological responses to a precision medicine-guided intervention with regards to white and gray matter in AD and mild cognitive impairment (MCI). METHODS: Clinical and neuroimaging data were compiled over a 9-month period from 25 individuals who were diagnosed with AD or MCI receiving individualized treatment plans. Structural T1-weighted MRI scans underwent segmentation and volumetric quantifications via Neuroreader. Longitudinal changes were calculated via annualized percent change of WM or GM ratios. RESULTS: Montreal Cognitive Assessment scores (p < 0.001) and various domains of the Computerized Neurocognitive Screening Vital Signs significantly improved from baseline to 9-month follow-up. There was regional variability in WM and GM atrophy or hypertrophy, but none of these observed changes were statistically significant after correction for multiple comparisons.

Longitudinal associations between self-reported sleep duration and cardiometabolic disease risk in corporate executives.

OBJECTIVE: This study aimed to determine the longitudinal associations between self-reported sleep duration and cardiometabolic disease (CMD) risk in corporate executives. METHODS: Self-reported sleep duration and lifestyle, occupational, psychological, and anthropometrical, blood pressure and blood marker variables were obtained from 1512 employees at annual health risk assessments in South Africa between 2016 and 2019. Gender-stratified linear mixed models, adjusting for age, lifestyle, occupational and psychological covariates were used to explore these longitudinal associations. RESULTS: Among women, shorter sleep duration was associated with higher body mass index (BMI) covarying for age only (ß with 95% confidence intervals: -0.19 [-0.36, -0.03]), age and occupational factors (-0.20 [-0.36, -0.03]) and age and psychological factors (-0.20 [-0.37, -0.03]). Among men, shorter sleep was associated with both BMI and waist circumference (WC) covarying for age only (BMI: -0.15 [-0.22; -0.08]; WC: -0.62 [-0.88; -0.37]); age and lifestyle factors (BMI: -0.12 [-0.21; -0.04]); WC: -0.016 [-0.92; -0.29], age and occupational factors (BMI: -0.20 [-0.22; 0.08]; WC: -0.62 [-0.88; -0.36]), and age and psychological factors (BMI: -0.15 [-0.22; -0.07]; WC: -0.59 [-0.86; -0.33]). Among men, shorter sleep was also longitudinally associated with higher CMD risk scores in models adjusted for age and lifestyle factors (CMD: -0.12 [-0.20; -0.04]) and age and psychological factors (CMD: -0.08 [-0.15; -0.01]). CONCLUSION: Corporate executives who report shorter sleep durations may present with poorer CMD risk profiles, independent of age, lifestyle, occupational and psychological factors. Addressing sleep health in workplace health programmes may help mitigate the development of CMD in such employees.

Precision Medicine Approach to Alzheimer's Disease: Rationale and Implications.

The neurodegenerative disease field has enjoyed extremely limited success in the development of effective therapeutics. One potential reason is the lack of disease models that yield accurate predictions and optimal therapeutic targets. Standard clinical trials have pre-determined a single treatment modality, which may be unrelated to the primary drivers of neurodegeneration. Recent proof-of-concept clinical trials using a precision medicine approach suggest a new model of Alzheimer's disease (AD) as a chronic innate encephalitis that creates a network insufficiency. Identifying and addressing the multiple potential contributors to cognitive decline for each patient may represent a more effective strategy. Here we review the rationale for a precision medicine approach in prevention and treatment of cognitive decline associated with AD. Results and implications from recent proof-of-concept clinical trials are presented. Randomized controlled trials, with much larger patient numbers, are likely to be significant to establishing precision medicine protocols as a standard of care for prevention and treatment of cognitive decline. Furthermore, combining this approach with the pharmaceutical approach offers the potential for enhanced outcomes. However, incorporating precision medicine approaches into everyday evaluation and care, as well as future clinical trials, would require fundamental changes in trial design, IRB considerations, funding considerations, laboratory evaluation, personalized treatment plans, treatment teams, and ultimately in reimbursement guidelines. Nonetheless, precision medicine approaches to AD, based on a novel model of AD pathophysiology, offer promise that has not been realized to date with monotherapeutic approaches.