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Physician-Reported Barriers and Facilitators to Thyroid Hormone Deprescribing in Older Adults
No full textBACKGROUND: Thyroid hormone is one of the most commonly prescribed medications in the United States. Misuse of and overtreatment with thyroid hormone is common in older adults and can lead to cardiovascular and skeletal adverse events. Even though deprescribing can reduce inappropriate care, no studies have yet explored specific barriers and facilitators to guide thyroid hormone deprescribing in older adults (defined as discontinuation of thyroid hormone when initiated without an appropriate indication or dose reduction in those overtreated).
METHODS: We conducted semi-structured interviews with 19 endocrinologists, geriatricians, and primary care physicians who prescribe thyroid hormone. Interviews were completed between July 2020 and December 2021 via two-way video conferencing. We used both an inductive and deductive content analysis guided by the Theoretical Domains Framework to evaluate transcribed and coded participant responses. Thematic analysis characterized themes related to barriers and facilitators to thyroid hormone deprescribing practices in older adults.
RESULTS: The most commonly reported barriers to thyroid hormone deprescribing were related to patient-level factors, followed by physician- and system-level factors. Patient factors included patients\u27 perceived need for thyroid hormone use and patient anxiety/concerns about potential side effects related to thyroid hormone dose reduction, patient lack of knowledge, and misinformation regarding deprescribing. Physician- and system-level barriers included clinic visit time constraints, physician inertia, physician lack of knowledge about deprescribing, perceived lack of sufficient patient follow-up, and electronic health record limitations. The most prominent physician-reported facilitators to thyroid hormone deprescribing were effective physician-to-patient communication, and positive physician-patient relationship, including patients\u27 trust in their treating physician.
CONCLUSION: Barriers and facilitators to thyroid hormone deprescribing in older adults were reported at multiple levels including patient-, physician-, and system-level factors. Interventions to improve thyroid hormone deprescribing in older adults should aim to improve patient education and expectations, increase multidisciplinary physician awareness, and overcome physician inertia
Icodec ONWARDS: A Review of the First Once-Weekly Diabetes Treatment for Nurse Practitioners and Physician Assistants
No full textBACKGROUND: Diabetes management is challenged by the complexity of treatment regimens and the need for frequent injections, affecting patient adherence and quality of life. Insulin icodec, a once-weekly basal insulin analog, represents a significant innovation, potentially simplifying diabetes care and improving outcomes.
OBJECTIVES: This review aims to evaluate the safety, efficacy, and clinical implications of insulin icodec for individuals with type 1 and type 2 diabetes, highlighting its potential to affect current treatment paradigms.
DATA SOURCES: A review was conducted comparing once-weekly insulin icodec with daily basal insulin analogs using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to ensure transparent reporting of systematic reviews. A search was performed in the following databases: PubMed, Google Scholar, Embase, and ClinicalTrials.gov, focusing on efficacy and safety outcomes.
CONCLUSIONS: Insulin icodec has demonstrated effective glycemic management and a safety profile comparable to daily basal insulins. Its extended half-life and steady-state glucose-lowering effect have the potential to reduce the burden of daily injections and improve patient adherence.
IMPLICATIONS FOR PRACTICE: The introduction of once-weekly insulin icodec represents an advancement in diabetes care. For front-line clinicians, this innovation aligns with the need for more straightforward medication regimens. Coupled with continuous glucose monitoring systems, it enables a more personalized and efficient approach to diabetes management, with the potential to improve patient satisfaction and clinical outcomes. This underscores the impact of integrating such advancements into practice, highlighting the role of nurse practitioners and physician assistants in adopting these innovations to optimize patient care
Twenty-year Trend of Mortality from Concomitant Sepsis and Acute Myocardial Infarction (Type 1 or Type 2) in the United States
No full textTemporary Amniotic Membrane Graft Placement for Treatment of Refractory Macular Holes
No full textPURPOSE: To report two patient cases demonstrating the management of refractory macular holes through the application of temporary thin amniotic membrane grafts, followed by subsequent graft removal upon achieving hole closure.
METHODS: Comprehensive chart and literature review was conducted utilizing the PubMed database.
RESULTS: We describe two patients who underwent repeat pars plana vitrectomy for treatment of refractory macular holes. In both cases, the epi-retinal placement of a thin amniotic membrane graft (AMG) was done to achieve hole closure. Following a period of retinal stabilization, the amniotic membranes were removed due to the healthy appearance of the outer retinal layers and the ellipsoid zone, ultimately resulting in an improved final visual acuity in both patients.
CONCLUSION: This case series demonstrates a new approach of using a temporary AMG to close refractory macular holes. After graft removal, both patients reported enhanced visual acuity and subjective visual improvement, accompanied by the stable closure of macular holes on serial OCT scans
The Impact of Single-Port Robotic Surgery: A Survey among Urology Residents and Fellows in the United States
No full textOur aim was to investigate the perception and future expectations of Single-Port (SP) surgery among urology trainees in the United States. A 34-item online survey was distributed to urological residency and fellowship programs across the US, covering demographic profiles, SP training opportunities, perceived educational impact, and future perspectives. Descriptive analysis and multivariable linear regression were used to assess predictors of SP adoption. 201 surveys were completed (28.6% completion rate). Among institutions with an SP platform, about 50% have used it regularly for over 2 years, though often in less than 50% of procedures. While robotic simulators are commonly available, only 17% offer both multi-port and SP simulators, and structured pre-clinical SP training is limited. Approximately 30% of respondents expressed concerns over limited hands-on experience and a steeper learning curve with SP. Around 40% felt that their robotic surgery exposure was negatively impacted by SP\u27s introduction. SP surgery\u27s benefits are seen mostly in the immediate post-operative period and a significant number of respondents foresee a major role for SP in urology. However, proficiency in SP surgery is not seen as crucial for career advancement or job opportunities. Academic job aspirations, SP platform availability, and SP surgery workload are predictors of future SP implementation. Trainees increasingly recognize the clinical benefits of SP procedures but express concerns about the potential negative impact on hands-on experience. Training programs should more systematically integrate SP technology into curricula. There is a correlation between training in high-volume SP centers and future SP adoption
Genetic Relationships and Biological Pathways Underlying Suicidality and Comorbid Mental Disorders: A Comprehensive Cross-Phenotype Analysis
No full textBACKGROUND: The co-occurrence of mental disorders and suicidality are frequently seen in epidemiology. One explanation lies in shared genetic liabilities, hence we aimed to investigate the phenotypic and genetic associations between multiple mental disorders and different levels of suicidality.
METHODS: Using UK Biobank (UKB) European individual data, we first evaluated the phenotypic and polygenic relationships between 12 mental disorders and gradient scales of suicidality (spanning suicidal ideation, suicide attempts, and suicidal death). Second, we used existing genome-wide association study (GWAS) summary statistics to estimate genetic correlations and to identify pleiotropic genes using a combination of statistical genetics tools. Summary statistics were accessed from: 1) the Psychiatric Genomics Consortium (major depressive disorder [MDD], bipolar disorder [BD], anxiety disorders [ANX], obsessive-compulsive disorder [OCD], anorexia nervosa [AN], autism spectrum disorder [ASD], attention deficit hyperactivity disorder [ADHD], schizophrenia [SCZ], cannabis use disorder [CUD], and post-traumatic stress disorder [PTSD]), 2) the Million Veterans Program (alcohol use disorder [AUD] and opioid use disorder [OUD]), and 3) their joint analysis (suicidality). Third, using shared genetic liabilities as instrument, we evaluated evidence for causal relationship between mental disorders and suicidality by structural equation models and Mendelian randomizations. Last, we accessed the All of Us (AoU) diverse cohort data for replication in non-European populations.
RESULTS: For UKB, 150,861 eligible individuals were retained after standard GWAS quality control. Eight out 12 mental disorders (MDD, BD, ANX, AUD, OCD, AN, ASD and ADHD) showed both significant phenotypic and polygenic correlations with gradient suicidality (false discovery rate \u3c 0.05). Among them, the impact of MDD and BD on suicidality were the most obvious (for MDD: OR=5.78 and 1.26 for phenotypic and polygenic level; for BD: OR=12.98 and 1.14 for phenotypic and polygenic level). Using GWAS summary statistics, we also observed positive global genetic correlations between those 8 mental disorders and suicidality (rg ranging from 0·25 to 0·68, p \u3c 0.001). Across pairs of suicidality and mental disorders, we identified 23 functional genes (including novel ones like BPTF, NOL11 and CACNG5) shared by five or more pairs. These genes were significantly enriched in two Gene Ontology sets: developmental process and regulation of biological process. We also identified unique genes within each pair which were enriched in different pathways (e.g., glutamatergic synapse for suicidality-MDD, negative regulation of biological process for suicidality-BD, and actin cytoskeleton for suicidality-AUD). Causal models indicated potential causality from genetic diatheses of MDD, BD, AUD, ADHD, and ASD to risk of suicidality. Multiple cross-phenotype associations with suicidality were also replicated in AoU African and Asian populations (e.g., p \u3c 0.05 for MDD and BD polygenic associations).
DISCUSSION: This study underscores the urgent need to address the shared and distinct genetic architecture of suicidality and related mental conditions. The combination of longitudinal population-level biobanks and disease-ascertained GWAS are warranted to enhance our understanding of their relationships. Our findings will provide insights into future suicide prevention and management among individuals with and without mental disorders.
DISCLOSURE: Nothing to disclose
Upstaging from cT1 to pT2 in Triple Negative and Her2 Positive Breast Cancer: an Opportunity to Identify cT1 Breast Cancer Patients for whom Neoadjuvant Chemotherapy Should be Considered
No full textIntroduction: The use of neoadjuvant chemotherapy (NAC) is considered for all subtypes of breast cancer (BC) ≥T2 or \u3eN0. In triple negative (TN) and Her2 positive (Her2+) BC cases, this decision is also driven by the availability of adjuvant therapies for patients with residual disease post NAC, which have been shown to impact survival. Primary surgery is the standard approach for cT1N0 TN and Her2+ BC. However, pathologic stage may be discordant with clinical stage, revealing pT2 or higher that would have benefited from NAC had they been identified as cT2. We aim to define the rate of cT1 to pT2 upstaging at our institution in TN or Her2 + BC undergoing primary surgery. Secondarily, we aim to identify any clinicopathologic factors that may predict cT1 to pT2 upstaging to better identify cT1 cases in which NAC should be considered. Methods: Our institutional IRB approved prospective breast cancer database was queried for all cT1N0 TN or Her2+ cases undergoing primary surgery from 2016 to 2021. Patient demographics, clinical characteristics, tumor biology, and clinical/pathologic staging were recorded. Univariate odds ratios and corresponding 95% Confidence intervals were assessed using logistic regression to examine associations with pT2. All analyses were performed using SAS 9.4. Results: We identified 335 cases, 38 were excluded by defined criteria, leaving 297 for analysis. Based on diagnostic breast imaging, 17 were cT1a, 91 were cT1b, and 189 were cT1c. Forty cases (13.5%) were upstaged from cT1 to pT2. Of these 40, 34 (85%) were cT1c, 27 (66%) of these cT1c cases were ≥ 15 mm based on preoperative imaging. On univariate analysis, the only significant predictor of pT2 upstaging for the entire population was size (\u3c 0.001). Biology, breast density and imaging modality were not significnt predictors of pT2 upstaging. Using a threshold for cT1 cases of \u3c 15 mm rather than ≤20 mm for primary surgery in our population would have resulted in a 4.4% pT2 upstage rate. Conclusions: Improved identification of the cT1 TN or Her2+ BC cases that are likely to upstage to pT@ is critical, as it has the potential to significantly affect survival outcomes due to the known benefit of NAC for T2 cases. In our population, utilizing a cT1 size threshold of \u3c 15 mm for upfront surgery would result in a lower rate of upstage to pT2 (4.4% versus 13.5%). This highlights the importance of consideration of NAC for cT1c cases ≥15 mm as it may have significant clinical implications on patient outcomes. Further studies to better predict T-stage in cT1c cases ≥15mm are needed
Atezolizumab in patients (pts) with tumor mutational burden (TMB)–high tumors from the TAPISTRY trial
No full textBackground: Studies have suggested that pts with TMB-high tumors could derive clinical benefit from atezolizumab, a PD-L1 inhibitor; however, these studies used inconsistent TMB cutoffs. We report efficacy and safety data of atezolizumab in adult and pediatric pts with TMB-high advanced/metastatic solid tumors from Cohort D of the TAPISTRY trial (NCT04589845), using two TMB cutoffs: ≥13 mutations [mut]/Mb and ≥16 mut/Mb. Methods: TAPISTRY is a phase II, global, open-label, multicohort basket trial evaluating the efficacy and safety of multiple therapies in pretreated pts with advanced/metastatic solid tumors. Pts in Cohort D had advanced unresectable/metastatic, PD-L1 inhibitor-naïve, TMB-high (≥13 mut/Mb) solid tumors. Atezolizumab was given every 21 days, at 1200 mg in pts ≥18 years old, and at ≥15 mg/kg (up to 1200 mg) in pts \u3c18 years old. Tumor responses were assessed per RECIST v1.1. Primary endpoint: objective response rate (ORR) by independent review committee (IRC) in pts with TMB ≥16 mut/Mb. Secondary endpoints included ORR by IRC in pts with TMB ≥13 mut/Mb, duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety. Results: At data cut-off (Nov 9, 2023), 150 pts with TMB ≥13 mut/Mb were enrolled. In the safety-evaluable population (n = 148), median age was 63 years (range 11–86); 56% of pts were male, and 56% had received ≥2 prior lines of therapy (median 2; range 0–14). The efficacy-evaluable population included 129 pts with TMB ≥13 mut/Mb (TMB ≥16 mut/Mb; n = 111); the most common tumor types were colorectal (n = 40; 31%), breast, and gastroesophageal cancer (n = 11 each; 9%). Key outcomes are presented (Table). After a median follow-up of 9.8 months, ORR by IRC was comparable between pts with TMB ≥16 mut/Mb (22.5%) and pts with TMB ≥13 mut/Mb (20.2%). Responses were seen across a variety of tumor types. DoR 6- and 12-month event-free rates were 79% and 72%, respectively. Median PFS was short, suggesting fast disease progression in non-responders. Fatigue (22%) and anemia (20%) were the most common adverse events. Safety of atezolizumab was consistent with its known profile. Conclusions: Atezolizumab was well tolerated and led to antitumor activity in pts with TMB-high solid tumors. Responses were seen across a variety of tumor types. Clinical trial information: NCT04589845
Longitudinal tissue-based evaluation of TIGIT expression in patients with pancreatic cancer: Effect of expression with advancing clinical stages and across racial groups
No full textBackground: While ground has been gained, pancreatic ductal adenocarcinoma (PDAC) continues to have a low 5-year survival of 13%. This is owed partially to a lack of early detection biomarkers and resistance to standard therapeutic options. TIGIT, an immune checkpoint receptor, is a marker of T-cell exhaustion and plays a key role in the inhibition of anti-tumor immune responses. TIGIT inhibitors are being explored in clinical trials in PDAC. Here we evaluate TIGIT expression in a cohort of PDAC patients and correlate level and intensity of expression with clinical parameters. We also examine changes in expression as the disease progresses from primary to metastatic disease. Methods: We performed RNAscope in situ hybridization (ISH) with a probe specific for human TIGIT mRNA on 82 formalin-fixed paraffin-embedded (FFPE) tissue samples. The cohort of tissue samples included 9 biopsies, 67 primary resections and 6 metastatic lesions. We evaluated the total TIGIT expression (%) as well as the intensity of TIGIT expression (% of cells with 3+ punctae, signifying putative immune cells), and compared these values between samples. Utilizing linear regression for continuous outcomes and logistic regression for binary outcomes, we tested for associations between TIGIT expression and clinical covariates. Results: Staining analysis showed that TIGIT expression did not differ significantly between racial groups. The mean percentage of TIGIT positive cells was 64.0%. High expression of TIGIT was associated with more advanced clinical stage (p \u3c 0.05). Evaluation of three longitudinal samples from the same patient revealed decreased TIGIT expression from the initial biopsy (41.6%) to resection (33.4%) and metastasis (2.8%). In these specimens, 3+ TIGIT expression also declined (2.1%, 1.2% and 0.02%, respectively). Conclusions: Anti-TIGIT therapy has potential to reverse immune suppression and, with other therapeutic modalities, may provide survival benefit. Here we demonstrate that increased TIGIT expression correlates with more advanced stage at diagnosis and also present data demonstrating that overall TIGIT expression, as detected by RNAscope ISH, may decrease as PDAC progresses to metastasis. As such, anti-TIGIT therapy may have important implications for evading an important mechanism of cancer progression
800.22 Transcatheter vs. Surgical Valve Replacement in Severe Aortic Stenosis with Small Annulus: A Meta-Analytical Review of Two-Year Outcomes
No full textBackground: The optimal approach for severe aortic stenosis (AS) patients with small aortic annulus (SAA) remains uncertain when comparing transcatheter (TAVR) and surgical aortic valve replacement (SAVR). Methods: We conducted a pooled analysis of data from observational studies and randomized controlled trials that compared TAVR and SAVR in patients with severe aortic stenosis and small aortic annulus. The key endpoints evaluated were all-cause mortality, stroke, and myocardial infarction over a 2-year follow-up period. We used inverse variance method with Paule-Mandel estimator for tauˆ2 and Hartung-Knapp adjustment for random effects model accounting for small study effect and heterogeneity in the current analysis. All analysis was carried out using R version 4.0.3. Results: The meta-analysis incorporated data from three studies, evaluating a total of 279 TAVR and 231 SAVR patients with severe aortic stenosis and small aortic annulus. The analysis demonstrated no significant difference in all-cause mortality at 2 years follow-up, with a pooled risk ratio of 0.82 (95% CI [0.56; 1.21]), and no heterogeneity (I2 = 0%) [Figure, PANEL A]. The risk of stroke was comparable between TAVR and SAVR, with a risk ratio of 1.34 (95% CI [0.06; 28.44]) and moderate heterogeneity (I2 = 59%) [Figure, PANEL B]. Myocardial infarction was also comparable between TAVR and SAVR, yielding a risk ratio of 0.66 (95% CI [0.10; 4.15]) with no detected heterogeneity (I2 = 0%) [Figure, PANEL C]. Conclusion: In patients with severe aortic stenosis and small aortic annulus, TAVR and SAVR reported comparable results in all-cause mortality, stroke, and myocardial infarction at 2 years. Selection of valve replacement therapy should be individualized, considering these findings. [Formula presented