A Scoping Review of Complementary and Alternative Medicine for Human Papillomavirus Infections and Cervical Dysplasia.

OBJECTIVE: The goal of this scoping review is to synthesize clinically relevant scientific literature on current complementary and alternative medications that address human papillomavirus (HPV) infections and cervical dysplasia. MATERIALS AND METHODS: A systematic search of published studies was performed December 2021 for the following concepts: human papilloma virus, cervical dysplasia, and complementary and alternative medicine (CAM). Relevant publications were identified by searching Ovid MEDLINE ALL, Embase, Cochrane Library, AMED, and MEDLINE databases, in addition to clinical trial databases. Data were extracted based on specific study selection criteria and analyzed by 3 authors independently using Covidence software. RESULTS: A total of 2324 studies were identified of which 56 met inclusion criteria. Treatment outcomes measured regression of HPV, improvement of cervical cytology, and/or regression of histopathology with varied definitions of success across all studies. The CAM therapies found to have the most clinical benefit and best supporting data via randomized control trials were topical mushroom ( Coriolus versicolor) gel, oral and topical selenium therapies, and oral indol-3-carbinol. Adverse events were reported in only 28/56 (50%) of included studies. CONCLUSIONS: The evidence for treating HPV and cervical dysplasia with CAM is of low quality because of lack of standardized, clinically relevant treatment outcomes, lack of standardization of products, and minimal reporting on adverse and long-term effects. Future large, randomized control trials are needed to further assess efficacy and safety of CAM therapies to address HPV and cervical dysplasia.

Importance Ranking of Electrocardiogram Rhythms: A Primer for Curriculum Development.

INTRODUCTION: Electrocardiogram interpretation is an essential skill for emergency and critical care nurses and physicians. There remains a gap in standardized curricula and evaluation strategies used to achieve and assess competence in electrocardiogram interpretation. The purpose of this study was to develop an importance ranking of the 120 American Heart Association electrocardiogram diagnostic labels with interdisciplinary perspectives to inform curriculum development. METHODS: Data for this mixed methods study were collected through focus groups and individual semi-structured interviews. A card sort was used to assign relative importance scores to all 120 American Heart Association electrocardiogram diagnostic labels. Thematic analysis was used for qualitative data on participants' rationale for the rankings. RESULTS: The 18 participants included 6 emergency and critical care registered nurses, 5 cardiologists, and 7 emergency medicine physicians. The 5 diagnoses chosen as the most important by all disciplines were ventricular tachycardia, ventricular fibrillation, atrial fibrillation, complete heart block, and normal electrocardiogram. The "top 20" diagnoses by each discipline were also reported. Qualitative thematic content analysis revealed that participants from all 3 disciplines identified skill in electrocardiogram interpretation as clinically imperative and acknowledged the importance of recognizing normal, life threatening, and time-sensitive electrocardiogram rhythms. Additional qualitative themes, identified by individual disciplines, were reported. DISCUSSION: This mixed-methods approach provided valuable interdisciplinary perspectives concerning electrocardiogram curriculum case selection and prioritization. Study findings can provide a foundation for emergency and critical care educators to create local ECG educational programs. Further work is recommended to validate the list amongst a larger population of emergency and critical care frontline nurses and physicians.

Exploration of spatial patterns of congenital anomalies in Los Angeles County using the vital statistics birth master file.

Research has shown linkages between environmental exposures and population health metrics such as low birth weight and incidence of congenital anomalies. While the exact causal relationship between specific environmental teratogens and suspected corresponding congenital anomalies has largely not been established, spatial analysis of anomaly incidence can identify potential locations of increased risk. This study uses the Vital Statistics Birth Master File to map and analyze the rates of congenital anomalies of births from non-smoking mothers 15-35 years old within Los Angeles County. Hot spot analysis shows that the distribution of congenital anomalies is not randomly distributed throughout the county and identified the Antelope Valley and San Gabriel Foothills as two areas with elevated incidence rates. These results are not explained by potential confounders such as maternal age, race, smoking status, or socioeconomic status and seem to correlate well with the concentration of atmospheric ozone. This approach demonstrates the value of using spatial techniques to inform future research efforts and the need to establish and maintain a comprehensive reproductive health surveillance system.

Vaginal Corrosion Due to Insertion of a 9-Volt Battery.

BACKGROUND: Batteries are known to cause damage to mucosal surfaces. Unfortunately, the timing of serious sequelae and recommendations for removal of a vaginally inserted battery in a premenopausal patient are not well characterized. This case report aims to detail the timeline of events and complications after vaginal insertion of a 9-volt alkaline battery and to further clarify the recommendation for urgent removal. CASE: A 24-year-old nulliparous woman with significant psychiatric and trauma history was admitted for ingestion and insertion of multiple foreign objects, including a 9-volt battery that she inserted into her vagina during her hospital admission. Examination under anesthesia was required for removal of the battery, with cervical and vaginal necrosis and partial-thickness burns noted. Removal occurred approximately 5.5 hours after insertion. Management included vaginal irrigation and topical estrogen. CONCLUSION: Given our findings of rapid and severe damage to the vaginal mucosa, urgent removal of a vaginally inserted battery is indicated.

Herbal supplement use among reproductive-aged women in an academic infertility practice.

Objective: To address the knowledge gap surrounding herbal medicine and supplement usage patterns and supplement-prescription medication interactions among patients seeking treatment for infertility. Design: Cross-sectional survey study. Setting: Academic infertility practice. Patients: Ninety-five reproductive-aged patients. Interventions: Not applicable. Main Outcome Measures: Use of herbal medications and supplements, baseline demographics, history of infertility treatments, and potential supplement-medication interactions. Results: We surveyed 95 participants with a median age of 35 years. Overall, 68.4% of patients reported ever having used supplements or herbal medicines in the past. Current use of herbal supplements and vitamins was reported by 53.7% and 93.7% of participants, respectively, with a median of 2 (range 19) supplements used per person. There were no significant associations between patient demographics, comorbidities, or infertility treatments with increased rates of supplement use. The most commonly used herbal supplements were: green tea (n = 14), chamomile (n = 12), peppermint (n = 9), turmeric (n = 8), elderberry (n = 7), ginger (n = 7), maca (6) with the most common modalities being pills/capsules (23.8%) and tea (42.3%). The most common reasons for use were: general health and wellness (24.5%), immune support (16.2%), stress (14.0%), and fertility (15.0%). Patients used maca (n = 5), chasteberry (n = 3), goji berry (n = 2), ginger (n = 2), yam-based progesterone (n = 2), and combination product (n = 2) for fertility purposes. A total of 7.9% of patients learned about these products from their general health care provider, and 33.3% of supplements were disclosed by patients to their provider. We identified 41 moderate-risk supplement-drug interactions, with 12 of these interactions attributed to infertility therapies. Based on the interaction checker, the most commonly proposed mechanisms of interaction were CYP3A4 and CYP2C19 inhibition. In terms of safety in pregnancy, cannabidiol and chasteberry were suggested to be "possibly unsafe in pregnancy," and red raspberry leaf "likely unsafe in pregnancy" without direct medical supervision. Conclusions: We found over two thirds of women seeking treatment for infertility reported past and over half reported current herbal medicine and supplement use. Notably, the Natural Medicines Interaction Checker suggested high rates of moderate-risk supplement-drug interactions and possible harmful effects in early pregnancy. Our results call for further investigation of clinically relevant supplement interactions with infertility therapies.

Herbal Supplement Use Among Adolescent and Young Adult Women in a Family Planning Clinic.

STUDY OBJECTIVE: We aimed to evaluate herbal medicine and supplement use patterns among adolescent and young adult women at a clinic focused on family planning. METHODS: We conducted a cross-sectional survey of patients (age 14-25) at an adolescent Title X clinic. Participants completed an electronic survey that assessed herbal medicine and supplement use, baseline demographic characteristics, and current contraceptive method. We evaluated supplement-drug interactions using the Natural Medicines database Interaction Checker. Quantitative analyses were performed using χ2 and independent medians tests. RESULTS: We enrolled 99 participants with a median age of 20 (15-24) years. Overall, 42.4% of patients reported ever having used supplements or herbal medicines, with 29.9% of patients reporting current supplement or herbal medicine use. Patients with higher education and private insurance were more likely to report a history of and current supplement use (P < .05). The most common herbal supplements reported were green tea (n = 26), cannabidiol (n = 17), and cranberry (n = 16), with 29.6% of participants reporting use to their general health care provider. The most common reasons for use were general health and wellness (29.1%), immune support (23.2%), stress (16.8%), and menstrual irregularities (6.0%). We found 62 moderate risk supplement-drug interactions, with 50 interactions attributed to hormonal contraceptive therapies. The most common interactions were via cytochrome P450 enzyme (CYP3A4 or CYP1A2) inhibition, decreased caffeine clearance, and potential hepatotoxicity. CONCLUSION: Adolescent and young adult women frequently reported past and current herbal medicine and supplement use, with high rates of moderate-risk supplement-drug interactions. Further research is needed to better elucidate these clinically relevant supplement-contraception interactions.

Modeling Diagnostic Expertise in Cases of Irreducible Uncertainty: The Decision-Aligned Response Model.

PURPOSE: Assessing expertise using psychometric models usually yields a measure of ability that is difficult to generalize to the complexity of diagnoses in clinical practice. However, using an item response modeling framework, it is possible to create a decision-aligned response model that captures a clinician's decision-making behavior on a continuous scale that fully represents competing diagnostic possibilities. In this proof-of-concept study, the authors demonstrate the necessary statistical conceptualization of this model using a specific electrocardiogram (ECG) example. METHOD: The authors collected a range of ECGs with elevated ST segments due to either ST-elevation myocardial infarction (STEMI) or pericarditis. Based on pilot data, 20 ECGs were chosen to represent a continuum from "definitely STEMI" to "definitely pericarditis," including intermediate cases in which the diagnosis was intentionally unclear. Emergency medicine and cardiology physicians rated these ECGs on a 5-point scale ("definitely STEMI" to "definitely pericarditis"). The authors analyzed these ratings using a graded response model showing the degree to which each participant could separate the ECGs along the diagnostic continuum. The authors compared these metrics with the discharge diagnoses noted on chart review. RESULTS: Thirty-seven participants rated the ECGs. As desired, the ECGs represented a range of phenotypes, including cases where participants were uncertain in their diagnosis. The response model showed that participants varied both in their propensity to diagnose one condition over another and in where they placed the thresholds between the 5 diagnostic categories. The most capable participants were able to meaningfully use all categories, with precise thresholds between categories. CONCLUSIONS: The authors present a decision-aligned response model that demonstrates the confusability of a particular ECG and the skill with which a clinician can distinguish 2 diagnoses along a continuum of confusability. These results have broad implications for testing and for learning to manage uncertainty in diagnosis.

Tamoxifen for the Treatment of Etonogestrel Implant-Associated Bleeding in an Adolescent Gynecology Practice.

OBJECTIVE: To describe clinical outcomes in a cohort of adolescent female patients using tamoxifen for the treatment of bothersome etonogestrel (ENG) implant-associated bleeding. DESIGN: Retrospective chart review SETTING: A tertiary children's hospital PARTICIPANTS: Adolescent female patients ages 12-21 seen between August 2016 and August 2019 with an ENG implant in place who received a tamoxifen prescription for the indication of implant-associated bleeding. INTERVENTIONS: None MAIN OUTCOME MEASURES: Main outcome measures were implant continuation rates, average time to implant discontinuation after tamoxifen prescription, reasons for implant removal, number of doses and timing of tamoxifen use, bleeding patterns, and adverse effects. RESULTS: A total of 67 patients met the inclusion criteria. The mean age of patients was 16.7 years old. Of the patients with available follow-up data, 49 out of 60 (81.7%) were still using the implant at 12 months, 29 out of 53 (54.7%) at 24 months, and 9 out of 40 (22.5%) at 36 months. The average time from tamoxifen prescription to implant removal was 12.1 months. Bothersome bleeding was the primary reason for ENG implant discontinuation (68.6%). No side effects from tamoxifen use were reported. CONCLUSION: Tamoxifen was well-tolerated among this cohort of patients and can be considered a treatment option to manage bothersome implant bleeding in adolescents.

A Challenging Case of Extensive Spontaneous Coronary Artery Dissection.

The detection of spontaneous coronary artery dissection (SCAD) causing myocardial infarction is integral in pursuing the appropriate management. Our case posed a diagnostic challenge, with Takotsubo cardiomyopathy and coronary embolism among the potential differential diagnoses upon the initial presentation. Extensive propagation of spontaneous coronary artery dissection subsequently resulted in a significant challenge to management requiring surgical revascularization. (Level of Difficulty: Intermediate.).

Gene and protein expression pilot profiling and biomarkers in an experimental mouse model of hypertensive glaucoma.

Glaucoma is a group of genetically heterogeneous neurodegenerative disorders causing the degeneration of the ganglion neurons of the retina. Increased intraocular pressure (IOP) is a hallmark risk factor promoting the death of ganglion neurons of the retina in glaucoma. Yet, the molecular processes underlying the degeneration of these neurons by increased IOP are not understood. To gain insight into the early molecular events and discover biomarkers induced by IOP, we performed gene and protein expression profiling to compare retinas of eyes with and without high IOP in a rodent model of experimental glaucoma. This pilot study found that the IOP-mediated changes in the transcription levels of a restricted set of genes implicated in peroxisomal and mitochondrial function, modulation of neuron survival and inflammatory processes, were also accompanied by changes in the levels of proteins encoded by the same genes. With the exception of the inflammatory markers, serum amyloid-A1 (SAA1) and serum amyloid-A2 (SAA2), the IOP-induced changes in protein expression were restricted to ganglion neurons of the retina and they were detected also in the vitreous, thus suggesting an early IOP-mediated loss of ganglion cell integrity. Interestingly, SAA1 and SAA2 were induced in retinal microglia cells, whereas they were reduced in sera of IOP-responsive mice. Hence, this study defines novel IOP-induced molecular processes, biomarkers and sources thereof, and it further validates the extension of the analyses herein reported to other genes modulated by IOP.

Medical Complications of Binge Eating Disorder.

Binge eating disorder (BED) is the most common eating disorder and is accompanied by multiple medical comorbidities, many of which are associated with obesity-related diseases. However, the BED itself is likely to confer additional risk factors. BED presents with medical symptoms in virtually every body system and can have devastating consequences on both quality and length of life. This review covers the major comorbidities of BED and highlights areas of ongoing research in this disorder.

Diagnoses associated with dietary supplement use in a national dataset.

OBJECTIVES: The purpose of this study was to determine if participant diagnosis, as determined by a health care provider, is associated with dietary supplement (DS) use. DESIGN/SETTING: Surveys from 1255 study participants aged 34-84, part of the Midlife in the US Study (MIDUS 2 Survey) Biomarker Project, were reviewed. Participant data included pharmaceutical use (prescription and over-the-counter medications (OTC)), clinical symptoms and diagnosis, and laboratory results. Associations were calculated between the above participant characteristics and DS use. MAIN OUTCOME MEASURES: Frequency of DS use for physician-reported diagnoses. RESULTS: Overall prevalence of DS use was 32.4%. Participants taking DS were more often female (p = .048), white (p < 0.001), and older (mean age 57 years, p < 0.001). Participants taking DS reported taking more OTC (p < .001) and prescription medications (p = .024), and had an increased number of chronic conditions (p = .004). Participants reporting physician-diagnosed diabetes were significantly less likely to be taking DS (p = .0066), while participants with eye disease (p = .001), high cholesterol (p = 0.041), cancer (p = 0.042), and arthritis (p = 0.044) were more likely to be taking DS than those without those conditions. No difference in DS use was found between patients with and without other identified medical conditions. After adjusting for age, race/ethnicity, and gender, only diabetes remained a significant predictor of decreased DS use (OR 0.588, CI 0.388-0.873, p = .01). CONCLUSIONS: Some physician-reported participant diagnoses were associated, positively or negatively, with DS use.

Healthcare Experiences of Underrepresented Lesbian and Bisexual Women: A Focus Group Qualitative Study.

Purpose: To understand the complex healthcare experiences of women identifying as lesbian or bisexual. who are also women of color, veterans, and/or 65 years of age and older. Methods: Inclusion criteria were age 25 or older, Los Angeles County resident, self-identification as a lesbian or bisexual woman, and as an African American, Latina, Asian-Pacific Islander, and/or a veteran. For the age 65 years and older group, participants were eligible regardless of their veteran status or race/ethnicity. Five focus groups were conducted (n=35) and the same questions were asked addressing their comfort interacting with healthcare providers, the provider knowing their sexual orientation, characteristics of a perfect provider, and barriers to care. Structured qualitative analyses were performed. Results: Participants identified concerns that providers often hold to heterosexual cultural norms. Participants varied on preferences for providers of the same race/ethnicity as themselves. Lesbians who are 65 years and older identified legal barriers as major concerns. All groups identified incorrect provider assumptions about sexual orientation and sexual practices as frequently compromising their care. Participants supported the idea of certification for providers skilled in lesbian, gay, bisexual, transgender, and queer (LGBTQ) health, but expressed skepticism that such programs would necessarily result in better care. Conclusion: Healthcare provider trainings need to address the specific concerns and experiences of underrepresented lesbian and bisexual women. Healthcare environments must be transformed to effectively address their needs. More research is needed on the separate healthcare experiences of specific marginalized populations related to their sexual orientation and/or gender identity.

Diastolic Function and Transcatheter Aortic Valve Replacement.

BACKGROUND: Little is known about baseline diastolic dysfunction and changes in diastolic dysfunction grade after transcatheter aortic valve replacement (TAVR) for aortic stenosis (AS) and its impact on overall outcomes. The aim of this study was to describe baseline diastolic dysfunction and changes in diastolic dysfunction grade that occur with TAVR and their relationship to mortality and rehospitalization. METHODS: This was a single-center study evaluating all TAVRs from January 2012 to June 2014. We compared parameters of diastolic dysfunction grade on pre-TAVR and 1 month post-TAVR echocardiograms for all patients undergoing the procedure. Descriptive statistics, Kaplan-Meier time-to-event analysis, and multivariate logistic regression were used. RESULTS: Of a sample size of 120 patients undergoing TAVR for symptomatic severe AS, 90 were included in the final analysis after excluding significant mitral valve disease. There were improvements in individual parameters of diastolic dysfunction grade such as lateral e' velocity, E/lateral e', and left atrial volume index (nonsignificant trend) in the setting of improvement in aortic valve area and gradients and functional class pre- and post-TAVR. Multivariate analysis revealed that baseline diastolic dysfunction grade, but not post-TAVR or changes in diastolic dysfunction grade, was associated with 1-year death (hazard ratio, 1.163; 95% CI, 1.049-1.277, P = .005) and combined death/cardiovascular hospitalization (hazard ratio, 1.174; 95% CI, 1.032-1.318; P = .018). CONCLUSIONS: In this single-center retrospective study of patients with symptomatic severe AS who underwent TAVR, several diastolic function parameters improved on echocardiography, but baseline diastolic dysfunction grade remained the most important echocardiographic factor associated with adverse 1-year outcomes.

Relation of dreams to waking concerns.

To test that dreams are influenced by the pre-sleep waking emotional concerns of the sleeper and have an effect on waking adaptation, 20 depressed and 10 control subjects, who were all going through a divorce, were enrolled in a repeated measures study lasting 5 months. A Current Concerns test was administered on three occasions before nights when every REM period was interrupted to record recalled mental content. The degree of waking concern about the ex-spouse correlated significantly with the number of dreams in which the former partner appeared as a dream character. Those who were in remission at the follow-up evaluation had a higher percentage of well-developed dreams than those who remained depressed. Dreams of the former spouse reported by those in remission differed from those who remained depressed in the expression of dream affect and in the within-dream linkage among units of associated memory material. Dreams of the former spouse that are reported by those who are not in remission lack affect and connection to other memories.

Reproductive health and the environment: Counseling patients about risks.

Endocrine-disrupting chemicals (EDCs) are associated with reproductive complications such as infertility, pregnancy complications, poor birth outcomes, and child developmental abnormalities, although not all chemicals of concern are EDCs. Pregnant patients and women of childbearing age need reasonable advice about environmental contaminants and reproductive health.

Association of chronic kidney disease with abnormal cardiac mechanics and adverse outcomes in patients with heart failure and preserved ejection fraction.

AIMS: Chronic kidney disease (CKD) is associated with worse outcomes in heart failure with preserved ejection fraction (HFpEF). Whether this association is due the effect of CKD on intrinsic abnormalities in cardiac function is unknown. We hypothesized that CKD is independently associated with worse cardiac mechanics in HFpEF. METHODS AND RESULTS: We prospectively studied 299 patients enrolled in the Northwestern University HFpEF Program. Using the creatinine-based CKD-Epi equation to calculate estimated glomerular filtration rate (eGFR), study participants were analysed by CKD status (using eGFR <60 mL/min/1.73 m(2) to denote CKD). Indices of cardiac mechanics (longitudinal strain parameters) were measured using speckle-tracking echocardiography. Using multivariable-adjusted linear and Cox regression analyses, we determined the association between CKD and echocardiographic parameters and clinical outcomes (cardiovascular hospitalization or death). Of 299 study participants, 48% had CKD. CKD (dichotomous variable) and reduced eGFR (continuous variable) were both associated with worse cardiac mechanics indices including left atrial (LA) reservoir strain, LV longitudinal strain, and right ventricular free wall strain even after adjusting for potential confounders, including co-morbidities, EF, and volume status. For example, for each 1-SD decrease in eGFR, LA reservoir strain was 3.52% units lower (P < 0.0001) after multivariable adjustment. Reduced eGFR was also associated with worse outcomes [adjusted hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.01-1.61 per 1-SD decrease in eGFR; P = 0.039]. The association was attenuated after adjustment for indices of cardiac mechanics (P = 0.064). CONCLUSION: In HFpEF, CKD is independently associated with worse cardiac mechanics, which may explain why HFpEF patients with CKD have worse outcomes. TRIAL REGISTRATION: NCT01030991.

Frailty Status and Outcomes After Transcatheter Aortic Valve Implantation.

Frailty is a syndrome of older adults associated with increased morbidity and mortality. We aimed to assess the impact of frailty status on outcomes after transcatheter aortic valve implantation (TAVI). We reviewed all 191 patients who underwent a modified Fried frailty assessment before TAVI between February 2012 and September 2015 at a single academic medical center, and we assessed the impact of preoperative frailty status on morbidity, mortality, and health care utilization after TAVI. Frailty, pre-frailty, and nonfrailty were present in 33% (n = 64), 37% (n = 70), and 30% (n = 57) of patients, respectively. Slowness (75% vs 54%, p = 0.003) and low physical activity (55% vs 31%, p = 0.001) were more common in women than men. With increasing frailty status, the proportion of women increased (35% nonfrail, 44% pre-frail, and 66% frail, p = 0.002) and stature decreased (1.68 ± 0.11 m nonfrail, 1.66 ± 0.11 m pre-frail, 1.62 ± 0.12 m frail, p = 0.028). There was no difference in post-TAVI 30-day mortality, stroke, major vascular injury, major or life-threatening bleeding, respiratory failure, mean hospital length of stay, 30-day hospital re-admission, or overall survival between groups. The rate of discharge to a rehabilitation facility increased with increasing frailty status (14% nonfrail, 22% pre-frail, and 39% frail, p = 0.005). Frailty was independently associated with discharge to a rehabilitation facility (odds ratio 4.80, 95% confidence interval 1.66 to 13.85, p = 0.004). In conclusion, the safety of TAVI is not affected by frailty status, but patients with frailty are less likely to be discharged directly home after TAVI.

Inhospital and Post-discharge Changes in Renal Function After Transcatheter Aortic Valve Replacement.

The aim of this study was to determine the influence of inhospital and post-discharge worsening renal function (WRF) on prognosis after transcatheter aortic valve replacement (TAVR). Severe chronic kidney disease and inhospital WRF are both associated with poor outcomes after TAVR. There are no data available on post-discharge WRF and outcomes. This was a single-center study evaluating all TAVR from June 1, 2008, to June 31, 2014. WRF was defined as an increase in serum creatinine of ≥0.3 mg/dl. Inhospital WRF was measured from day 0 until discharge or day 7 if the hospitalization was >7 days. Post-discharge WRF was measured at 30 days after discharge. Descriptive statistics, Kaplan-Meier time-to-event analysis, and multivariate logistic regression were used. In a series of 208 patients who underwent TAVR, 204 with complete renal function data were used in the inhospital analysis and 168 who returned for the 30-day follow-up were used in the post-discharge analysis. Inhospital WRF was seen in 28%, whereas post-discharge WRF in 12%. Inhospital and post-discharge WRF were associated with lower rates of survival; however, after multivariate analysis, only post-discharge WRF remained a predictor of 1-year mortality (hazard ratio 1.18, p = 0.030 for every 1 mg/dl increase in serum creatinine). In conclusion, the rate of inhospital WRF is higher than the rate of post-discharge WRF after TAVR, and post-discharge WRF is more predictive of mortality than inhospital WRF.

Antianginal efficacy of omapatrilat in patients with chronic angina pectoris.

Angiotensin-converting enzyme inhibition is not an effective antianginal therapy. Experimental data suggest that broader vasopeptidase inhibition may decrease the magnitude of demand-induced myocardial ischemia. A randomized, double-blind, placebo controlled parallel study evaluated omapatrilat, an inhibitor of angiotensin-converting enzyme and neutral endopeptidase. The primary objective was to compare maximum duration of exercise at peak plasma concentrations. Exercise treadmill studies were performed in 348 patients who had chronic angina at baseline and after 4 weeks of therapy with 80 mg/day omapatrilat or placebo. Safety data were collected and reported for all patients. Treadmill exercise duration at peak was significantly prolonged in the omapatrilat group compared with the placebo group (76.6 +/- 84.2 vs 28.7 +/- 82.2 seconds difference from baseline, p <0.001). Similar statistically significant increases were seen in time to onset of level III/IV angina and time to onset of >/=0.1-mV ST-segment depression (p <0.001). The significant improvements in exercise duration and measurements of myocardial ischemia were not sustained 20 to 28 hours after dosing. Omapatrilat was generally well tolerated in this predominantly normotensive population. The incidence of serious adverse events was 5.2% in the 2 groups. Thus, omapatrilat, an investigational vasopeptidase inhibitor, is effective in prolonging exercise duration and parameters of demand-induced myocardial ischemia in patients who have chronic angina at peak concentrations. The data confirm the proof of principle that broader vasopeptidase inhibition beyond angiotensin-converting enzyme inhibition is required to alleviate symptoms of chronic angina.