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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 tau^2 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
Endoscopic Endonasal Pituitary Sacrifice for Selected Complex Tumors with Retrochiasmatic and Retroclival Extension: Surgical Anatomy, Step-by-Step Operative Technique and Case Series
No full textBackground: Tumors located in the retrochiasmatic region with extension to the third ventricle might be difficult to access when the pituitary-chiasmatic corridor is narrow. Similarly, tumor extension into the retroclival space poses a surgical challenge. Pituitary transposition techniques have been developed to gain additional access to the retroclival space. However, when preoperative pituitary function is already impaired or the risk for postoperative panhypopituitarism (PH) is considered particularly high, removal of the pituitary gland might be the preferred option. Objective: Aim of this study is to describe the relevant surgical anatomy, the operative steps and our clinical experience with the endoscopic endonasal pituitary sacrifice (EE-PS) technique. Methods: Anatomical dissections of five postmortem specimens were performed. In addition, a retrospective analysis of clinical data was performed to report clinical characteristics, indications, and outcomes. Results: After a standard endoscopic endonasal approach, a wide exposure of the sella turcica and anterior walls of the cavernous sinus (CS) is performed. The boundaries of the bony exposure are as follows: the lateral opticocarotid recesses laterally, the limbus sphenoidale superiorly, and the sellar floor inferiorly. After opening of the dura, the gland is mobilized off the medial walls of the CS ([Figs. 1A] and [2A]). The descending branches of the superior hypophyseal artery are coagulated and the stalk transected ([Fig. 1B] and [2B]). After removal of the gland, bilateral posterior clinoidectomy followed by drilling of the dorsum sellae is performed ([Figs. 1C] and [2C]). The dura is opened again to access the hypothalamic region, interpeduncular and prepontine cisterns ([Figs. 1D] and [2D]). A total of 13 patients underwent EE-PS. The cohort comprised 10 (77%) craniopharyngiomas, 2 (15%) teratomas, and 1 (8%) hemangioblastoma. Nine (69%) patients had partial or complete anterior gland dysfunction preoperatively while 6 (46%) had preoperative diabetes insipidus. Due to the specific tumor configuration, the chance of preserving endocrine function was estimated to be very low in patients with intact function. The main reasons for PS were impaired surgical accessibility to the retrochiasmatic and retroclival space. Ten patients (77%) had gross total tumor resection (GTR) and 3 (23%) had a near total resection. Two (15%) patients experienced a postoperative cerebrospinal fluid leak, requiring surgical revision. Illustrative case 1: A 15-year-old male with a craniopharyngioma and partial pituitary dysfunction. The lesion extended extensively to the retrochiasmatic and retroclival space ([Fig. 3A, B]), which justified EE-PS. GTR could be achieved without hypothalamic injury ([Fig. 3C, D]). Illustrative case 2: A 16-year-old male with a nongerminomatous germ cell tumor ([Fig. 4A]) and PH. Despite chemotherapy, a vital tumor portion remained in the hypothalamic region ([Fig. 4B]). Due to the very limited pituitarychiasmatic corridor and the narrow space between the chiasm and the dorsum sella, PS was deemed necessary to access the retrochiasmatic space. GTR was achieved with no complications ([Fig. 4C, D]). Conclusion:: When preoperative pituitary function is already impaired or the risk for postoperative PH is considered particularly high, PS is a feasible surgical option to improve visibility and accessibility to the retroclival and retrochiasmatic space, thus increasing tumor resectability. (Figure Presented)
238 Reduction in opiate administration in emergency department patients following implementation of alternatives to opiates program
No full textBackground and Objectives: The opioid overdose epidemic has worsened causing 80,000 deaths per year in the US. Alternatives to Opiates (ALTO) programs are pain management algorithms that support emergency department (ED) clinicians to treat pain using non-opiate medications, decreasing patient exposure to opiates. We developed an ALTO program to reduce administration of opiate medications within 9 EDs of a regional health system. We targeted a 30% reduction in morphine milliequivalents (MME) administered in the ED per hour of length of stay (LOS).
Methods: A multi-disciplinary group developed an ALTO program using existing practice patterns and available literature and implemented a “Quicklist” in the electronic medical record to organize orders for non-opiate analgesics, allowing for greater ease of ordering. The ALTO program was implemented with preceding education, in the form of text resources and in-person forums, provided to ED clinicians and nursing staff. The program was implemented in November 2019. Feedback regarding the program was communicated at 4-month intervals via email. All 9 EDs participated in implementation and maintenance of the ALTO program and have an annual volume of nearly 450,000 patient visits. We calculated the total number of MMEs per encounter using standard conversion factors as well as the total number of ED LOS hours during the study period. These were used to calculate the MME per hour of ED LOS, which was then compared between the 36-month baseline period and the 47-month post-implementation period.
Results: In the 36-month period prior to ALTO implementation there were 4,937,743?MME administered system-wide to patients across 7,890,174 total ED LOS hours for an average of 0.63?MME administered per hour of ED LOS. In the 47-month period post-ALTO implementation there were 4,330,151?MME administered over 10,169,620 total ED LOS hours for an average of 0.43?MME administered per hour of ED LOS. These results demonstrate a 31.7% decrease in opiates administered as measured in MME per hour of ED LOS.
Conclusion: The ALTO program was associated with a decrease in opiate administration across a regional health system with a large annual patient volume. Standardized opiate administration as measured by MME per hour of ED LOS can help account for variables including fluctuations in volume and boarding. Continued program education is needed as is further study on associated patient-centered outcomes
P3.12D.07 Divarasib Versus Adagrasib or Sotorasib in Pretreated KRAS G12C+ Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)
No full textIntroduction: KRAS G12C mutations occur in approximately 12% of patients with NSCLC. Patients with advanced/metastatic KRAS G12C+ NSCLC who have previously received standard-of-care therapies (platinum-based chemotherapy, immunotherapy, or a combination of both) have a poor prognosis. Adagrasib and sotorasib are oral, selective KRAS G12C inhibitors with accelerated FDA and conditional EMA approvals for the treatment of patients with previously treated advanced/metastatic KRAS G12C+ NSCLC. However, an unmet need remains for more effective treatments with acceptable safety and tolerability profiles to improve patient outcomes. Divarasib is an oral, selective, KRAS G12C inhibitor previously shown to be 5-20 times as potent and ≤50 times as selective for KRAS G12C in vitro as adagrasib and sotorasib. Divarasib monotherapy (≤400mg once daily [QD]) previously demonstrated encouraging antitumor activity and an acceptable safety profile in patients with advanced/metastatic KRAS G12C+ solid tumors, including NSCLC (confirmed objective response rate [ORR]: 56.4%, 95% CI 39.6-72.2; progression-free survival [PFS]: 13.7 months, 95% CI 8.1-not estimable, in patients with NSCLC; 400mg dose). The observed adverse events were mostly low grade, manageable, and reversible. The phase 3 trial presented here will evaluate the efficacy and safety of divarasib versus adagrasib or sotorasib in patients with previously treated KRAS G12C+ advanced/metastatic NSCLC. Methods: This phase 3, randomized, active control, open-label multicenter study (EudraCT: 2024-510908-37-00) will enroll patients aged ≥18 years with histologically/cytologically confirmed, unresectable, advanced/metastatic (stage IIIC or IV) NSCLC harboring a KRAS G12C mutation (Figure). Patients must have experienced disease progression on ≥1 prior systemic therapy in the metastatic setting, have measurable disease per RECIST v1.1, and Eastern Cooperative Oncology Group performance status (ECOG PS) 0/1. Prior KRAS inhibitor therapy is not permitted. Patients will be randomized 1:1 to receive divarasib or either adagrasib or sotorasib (based on local approval status and investigator’s choice) until disease progression, intolerable adverse events, consent withdrawal, death, or study termination. Tumor assessments will occur at screening, every six weeks for the initial 48 weeks, and every nine weeks thereafter. The primary endpoint is PFS per RECIST v1.1. Secondary endpoints include: overall survival; patient-reported outcomes (time to confirmed deterioration of cough [EORTC QLQ-LC13], dyspnea, or physical functioning [both EORTC QLQ-C30]); ORR and duration of response per RECIST v1.1; and safety. [Formula presented] Keywords: Advanced NSCLC, Divarasib, KRAS G12C+ NSCL
Is 70% Achievable? Hospital-Level Variation in Rates of Cardiac Rehabilitation Use Among Medicare Beneficiaries
No full textBACKGROUND: Despite national goals to enroll 70% of cardiac rehabilitation (CR)-eligible patients, enrollment remains low.
OBJECTIVES: The purpose of this study was to evaluate how the treating hospital influences CR enrollment nationally.
METHODS: We included Fee-for-Service Medicare beneficiaries aged ≥66 years who were hospitalized for acute myocardial infarction, coronary artery bypass grafting, percutaneous coronary intervention, or heart valve repair/replacement. We examined: 1) a risk-standardized model to assess comparative hospital rates; 2) a linear regression model to identify hospital factors associated with rates of risk-standardized CR; and 3) a hierarchical generalized linear model to calculate the hospital median OR.
RESULTS: At 3,420 hospitals, we identified 264,970 eligible patients. A minority of hospitals (n = 1,446; 38%) performed cardiac surgery, but these hospitals cared for the majority (n = 242,875; 92%) of all eligible patients. Subsequent analyses were limited to these hospitals. The median risk-standardized CR enrollment rate was low (22%) and varied 10-fold across hospitals (10th, 90th percentile: 3%, 42%). Factors associated with higher hospital performance were Midwest location, higher number of hospital beds, directly affiliated CR program, and \u3c1 mile distance between the hospital and closest CR facility. The national hospital median OR was 2.1.
CONCLUSIONS: The treating hospital plays a key role in facilitating CR enrollment after discharge. Fewer than 1% of U.S. hospitals achieved a risk-standardized CR enrollment rate of \u3e70%. Hospitals with cardiac surgery capability care for more than 90% of all CR-eligible patients and may be a logical place to focus improvement efforts
Does implementation of office based addiction treatment by a nurse care manager increase the duration of OUD treatment in primary care? A secondary analysis of the PROUD randomized control trial
No full textBACKGROUND: Implementation of office-based addiction treatment (OBAT) by nurse care managers increases overall use of OUD medication, but it is unknown whether it increases treatment duration among treated patients.
METHODS: The Primary Care Opioid Use Disorders Treatment (PROUD) trial was a pragmatic, cluster-randomized trial testing whether implementation of OBAT increased OUD treatment in 12 primary care clinics in 6 systems. One of 2 clinics per system was randomized to implement OBAT (intervention), the other, usual care (UC). We evaluated treatment duration for the 3 years after nurses began seeing patients at clinics randomized to intervention vs. UC. The primary sample included patients newly initiating OUD medication; the secondary sample included patients with ongoing OUD medication. The primary outcome was percentage of days with OUD medications after treatment initiation, modeled using linear generalized estimating equations (GEE). Modified Poisson GEE models assessed secondary outcomes (≥80 % of days covered, ≥6 months on treatment).
RESULTS: In adjusted analyses, the mean difference between intervention and UC in percent days treated was 6.3 % (95 % CI -9.6 %, 22.1 %) in the primary sample and 2.3 % (95 % CI -36.4 %, 31.8 %) in the secondary sample. There was no significant difference in treatment duration between intervention and UC patients in either primary or secondary outcomes.
CONCLUSIONS: Implementation of OBAT in this trial did not measurably increase duration of medication treatment among those treated for OUD compared to UC, suggesting that benefits of OBAT, at least in this trial, largely reflect increases in treatment access
Response to ritlecitinib with or without narrow-band ultraviolet B add-on therapy in patients with active nonsegmental vitiligo: Results from a phase 2b extension study
No full textBACKGROUND: Ritlecitinib demonstrated efficacy in a phase 2b trial of nonsegmental vitiligo.
OBJECTIVE: To evaluate the efficacy and tolerability of ritlecitinib with add-on narrow-band ultraviolet B (nbUVB) phototherapy in patients with nonsegmental vitiligo.
METHODS: Following a 24-week, placebo-controlled, dose-ranging period, patients received ritlecitinib 200 mg for 4 weeks then 50 mg for 20 weeks, with or without nbUVB phototherapy 2x/week. Missing data were handled using last observation carried forward and observed case (OC).
RESULTS: Forty-three patients received ritlecitinib + nbUVB and 187 received ritlecitinib-monotherapy. Nine patients receiving ritlecitinib + nbUVB discontinued due to nbUVB group-specific efficacy criteria requiring \u3e10% improvement in % change from baseline (% change from baseline) in Total-Vitiligo Area Scoring Index at week 12. At week 24, mean % change from baseline in Facial-VASI score was -57.0 vs -51.5 (last observation carried forward; P = .158) and -69.6 vs -55.1 (OC; P = .009), for ritlecitinib + nbUVB vs ritlecitinib-monotherapy, respectively. Mean % change from baseline in Total-Vitiligo Area Scoring Index at week 24 was -29.4 vs -21.2 (last observation carried forward; P = .043) and -46.8 vs -24.5 (OC; P \u3c .001), respectively. nbUVB addition to ritlecitinib was well tolerated with no new safety signals.
LIMITATIONS: Exploratory analysis; discontinuation criterion applied only to the ritlecitinib + nbUVB group; small sample size.
CONCLUSION: Ritlecitinib alone and with nbUVB therapy improved facial and total body repigmentation and was well tolerated. Adding nbUVB may improve ritlecitinib efficacy
Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel in Participants With Moderate-to-Severe Acne: The Patient Journey
No full textINTRODUCTION: Topical clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (CAB) gel is the only fixed-dose, triple-combination formulation approved for acne treatment. In 3 clinical studies of participants with moderate-to-severe acne, CAB demonstrated superior efficacy to vehicle and component dyads, with good safety and tolerability. Detailed efficacy/safety data from individual clinical study participants are presented.
METHODS: In two phase 3 (NCT04214652, NCT04214639) randomized, double-blind, 12-week studies, participants aged at least 9 years with moderate-to-severe acne were randomized to once-daily CAB or vehicle gel. Descriptive data - including lesion count changes, treatment success (at least 2-grade reduction from baseline in Evaluator\u27s Global Severity Score and clear/almost clear skin), compliance, treatment-emergent adverse events (AEs), and cutaneous safety/tolerance assessments - were summarized from 6 CAB-treated cases.
RESULTS: By week 12, all cases achieved \u3e70% lesion reductions, 4/6 achieved treatment success, and 1/6 achieved a 2-grade reduction in severity. All cases were compliant with CAB treatment. No cases reported serious AEs. Transient increases occurred on cutaneous safety and tolerability assessments, with scores generally decreasing back to/below baseline levels by week 12.
CONCLUSIONS: In two phase 3 clinical trials, fixed-dose, triple-combination CAB demonstrated good efficacy/safety. All 6 CAB-treated cases achieved substantial (\u3e70%) lesion reductions, with 5/6 achieving treatment success or 2-grade reduction in severity by week 12. Transient cutaneous safety/tolerability severity increases generally resolved to baseline values by week 12. These clinical study cases reinforce the importance of patient education regarding adherence, expectations, and AEs