Coronary artery disease and outcomes following transcatheter aortic valve implantation.

BACKGROUND: Aortic stenosis is a life-limiting condition for which transcatheter aortic valve implantation (TAVI) is an established therapy. Coronary artery disease (CAD) is frequently found in this patient group and optimal management in these patients remains uncertain. OBJECTIVES: We sought to examine the association of coexistent CAD on mortality and hospital readmission in patients undergoing TAVI. METHODS: In this observational cohort study, we examined patients who underwent TAVI and segregated them by the presence of obstructive epicardial CAD. The primary outcome was 3-year mortality with secondary outcomes being readmission for (1) all-causes, (2) a MACE (Major Adverse Cardiovascular Event) composite endpoint and (3) acute coronary syndrome. Subsidiary outcomes included patient angina and breathlessness scores. RESULTS: 898 patients underwent TAVI, of which 488 (54.3%) had unobstructed coronary arteries and 410 (45.7%) had obstructive CAD. Overall, n=298 (33.2%) patients experienced the primary mortality endpoint with no significant difference when stratified according to CAD (n=160 (32.9%) vs n=136 (33.2%), HR 0.98, CI 0.78 to 1.24). After multivariate analysis, the presence of CAD had no effect on the primary outcome (HR 0.98, CI 0.68 to 1.40). There was no significant difference in readmission for any cause (n=181, 37.1% (CAD) vs n=169, 41.2% (no CAD), p=0.23), including no significant difference on readmission for MACE (n=48, 9.8% (CAD) vs n=45, 11.0% (no CAD), p=0.11). CAD at the time of TAVI also did not alter breathlessness or angina scores before/after TAVI (p>0.05). CONCLUSION: Coexistent CAD had no significant association with mortality, any-cause readmission or symptoms for patients undergoing TAVI in our cohort.

Aortic stenosis in the time of COVID-19: Development and outcomes of a rapid turnaround TAVI service.

The COVID-19 pandemic has resulted in the cancellation of many elective surgical procedures. This has led to reports of an increase in mortality for patients with non-Covid health conditions due to delayed definitive management. Patients with severe aortic stenosis have a high annual mortality if left untreated. These patients are at risk due to the reduced number of surgical aortic valve replacements and competition for intensive care facilities during the COVID-19 pandemic. This case series suggests that the minimally invasive transcatheter aortic valve implantation is safe to continue during the COVID-19 pandemic with adjustments to the patient pathway to minimize hospital stay and to reduce patient and staff exposure. This helps to reduce the delay of definitive treatment for patients with severe aortic stenosis.

Design and Preclinical Development of TransCon PTH, an Investigational Sustained-Release PTH Replacement Therapy for Hypoparathyroidism.

Hypoparathyroidism (HP) is a condition of parathyroid hormone (PTH) deficiency leading to abnormal calcium and phosphate metabolism. The mainstay of therapy consists of vitamin D and calcium supplements, as well as adjunct Natpara (PTH(1-84)). However, neither therapy optimally controls urinary calcium (uCa) or significantly reduces the incidence of hypercalcemia and hypocalcemia. TransCon PTH, a sustained-release prodrug of PTH(1-34) in development for the treatment of HP, was designed to overcome these limitations. To determine the pharmacokinetics and pharmacodynamics of TransCon PTH, single and repeat s.c. dose studies were performed in rats and monkeys. TransCon PTH demonstrated a half-life of 28 and 34 hours in rats and monkeys, respectively. After repeated dosing, an infusion-like profile of the released PTH, characterized by low peak-to-trough levels, was obtained in both species. In intact rats and monkeys, daily subcutaneous administration of TransCon PTH was associated with increases in serum calcium (sCa) levels and decreases in serum phosphate levels (sP). In monkeys, at a single dose of TransCon PTH that increased sCa levels within the normal range, a concurrent decrease in uCa excretion was observed. In 4-week repeat-dose studies in intact rats and monkeys, uCa excretion was comparable to controls across all dose levels despite increases in sCa levels. Further, in a rat model of HP, TransCon PTH normalized sCa and sP levels 24 hours per day. This was in contrast to only transient trends toward normalization of sCa and sP levels with an up to 6-fold higher molar dose of PTH(1-84). After repeated dosing to HP rats, uCa excretion transiently increased, corresponding to increases in sCa above normal range, but at the end of the treatment period, uCa excretion was generally comparable to sham controls. TransCon PTH was well tolerated and the observed pharmacokinetics and pharmacodynamics were in line with the expected action of physiological replacement of PTH. © 2019 American Society for Bone and Mineral Research.

Experience of associative stigma in parents of adolescents at risk for psychosis.

AIM: This qualitative study examined the lived experience of associative stigma for parents of adolescents at clinical high risk for psychosis. A central goal was to empower families to tell their stories and to use the themes that emerge from this narrative data to make recommendations that might support families coping with a loved one being diagnosed with risk for psychosis. METHODS: Twelve parents of adolescents diagnosed with the clinical high risk for psychosis syndrome were interviewed using a semi-structured approach. The qualitative study employed Interpretative Phenomenological Analysis (IPA) to focus on experiences of associative stigma and the way parents make sense of these experiences. RESULTS: From these interviews, the researcher identified themes and subthemes categorized into major domains that represent topics particularly relevant to these 12 parents. Two main domains emerged as particularly salient to parents' experiences with associative stigma: perceptions of stigma and coping with stigma. CONCLUSIONS: Participants' insights demonstrated increased experience of stigma associated with psychotic-like symptoms as compared to other psychiatric symptoms, attempts to balance fighting against stigma with the privacy needs of adolescents, and participation in research as less stigmatizing than non-specialty care. Stigma impacted treatment-seeking and participation in family groups that were seen as both potentially supportive and threatening. The interviews provided an opportunity for these families to voice their unique experiences, which expands the literature on the topic of caregivers of adolescents at risk for psychosis as treatment programs for the clinical high risk syndrome expand across the United States.

Depression screening by physical therapists: Practices, beliefs, barriers.

BACKGROUND: Depression, a common comorbidity encountered in physical therapy (PT) practice, negatively impacts outcomes. There is limited knowledge of PT practice patterns relative to screening for depression. OBJECTIVE: Objectives were to describe beliefs regarding depression, and identify practice patterns and perceived barriers regarding screening for depression among APTA Board Certified Orthopedic Clinical Specialist (OCS) PTs. METHODS: Surveys were distributed to all PT OCSs in the US; 416 responses were analyzed. Descriptive, univariate and multiple regression analyses were performed. RESULTS: Ninety-five percent of respondents believed that depression has a moderate to high influence on PT outcomes, whereas 68% believed a pre-existing diagnosis of depression influences the plan of care. Most believed that 20% or more of their current patients presented with symptoms of depression. Nevertheless, only 18% formally screen for depression during the initial evaluation. Those with formal depression screening education were 2.3 times more likely to screen at initial examination. Common barriers to screening included lack of department policy, limited knowledge and lack of follow-up resources. CONCLUSIONS: Formal screening did not occur as frequently as expected, given the belief regarding depression's impact on plan of care and outcomes. Addressing barriers may assist in greater compliance with recommended screening guidelines.

How should I treat severe symptomatic aortic stenosis with transcatheter aortic valve implantation in a patient with right aortic arch?

BACKGROUND: An 84-year-old man suffering from dyspnoea on mild exertion and a 10-year history of mitral valve replacement with a mechanical prosthesis presented to our department. The patient had an isolated right aortic arch. INVESTIGATION: Transthoracic echocardiography demonstrated severe LV systolic dysfunction (EF 25%), good function of the previously implanted mechanical prosthesis and severe aortic stenosis. Multislice computed tomography confirmed the presence of an isolated right aortic arch with mirror-image branching. DIAGNOSIS: Severe symptomatic aortic stenosis in a patient with right aortic arch at high risk for surgical reintervention. MANAGEMENT: Transcatheter aortic valve implantation using conventional delivery system.

Stereoselective synthesis of enantiomerically pure nupharamine alkaloids from castoreum.

An animalic note: The first total synthesis of the all-cis nupharamine 2, an alkaloid from beaver castoreum, is based on the stereoselective domino Mannich-Michael reaction of N-galactosylfurylaldimine to give 1 (Piv = pivaloyl), subsequent conjugate cuprate addition, and stereoselective protonation of the enolate. These reactions are all controlled by the carbohydrate. Protonation of the enolate after cleavage of the auxiliary leads to epimer 3.