Reproductive Justice: A Case-Based, Interactive Curriculum.

Introduction: Reproductive injustices such as forced sterilization, preventable maternal morbidity and mortality, restricted access to family planning services, and policy-driven environmental violence undermine reproductive autonomy and health outcomes, with disproportionate impact on historically marginalized communities. However, curricula focused on reproductive justice (RJ) are lacking in medical education. Methods: We designed a novel, interactive, case-based RJ curriculum for postclerkship medical students. This curriculum was created using published guidelines on best practices for incorporating RJ in medical education. The session included a prerecorded video on the history of RJ, an article, and four interactive cases. Students engaged in a 2-hour small-group session, discussing key learning points of each case. We evaluated the curriculum's impact with a pre- and postsurvey and focus group. Results: Sixty-eight students participated in this RJ curriculum in October 2020 and March 2021. Forty-one percent of them completed the presurvey, and 46% completed the postsurvey. Twenty-two percent completed both surveys. Ninety percent of respondents agreed that RJ was relevant to their future practice, and 87% agreed that participating in this session would impact their clinical practice. Most respondents (81%) agreed that more RJ content is needed. Focus group participants appreciated the case-based, interactive format and the intersectionality within the cases. Discussion: This interactive curriculum is an innovative and effective way to teach medical students about RJ and its relevance to clinical practice. Walking alongside patients as they accessed reproductive health care in a case-based curriculum improved students' comfort and self-reported knowledge on several RJ topics.

Population attitudes toward contraceptive methods over time on a social media platform.

BACKGROUND: Contraceptive method choice is often strongly influenced by the experiences and opinions of one's social network. Although social media, including Twitter, increasingly influences reproductive-age individuals, discussion of contraception in this setting has yet to be characterized. Natural language processing, a type of machine learning in which computers analyze natural language data, enables this analysis. OBJECTIVE: This study aimed to illuminate temporal trends in attitudes toward long- and short-acting reversible contraceptive methods in tweets between 2006 and 2019 and establish social media platforms as alternate data sources for large-scale sentiment analysis on contraception. STUDY DESIGN: We studied English-language tweets mentioning reversible prescription contraceptive methods between March 2006 (founding of Twitter) and December 2019. Tweets mentioning contraception were extracted using search terms, including generic or brand names, colloquial names, and abbreviations. We characterized and performed sentiment analysis on tweets. We used Mann-Kendall nonparametric tests to assess temporal trends in the overall number and the number of positive, negative, and neutral tweets referring to each method. The code to reproduce this analysis is available at https://github.com/hms-dbmi/contraceptionOnTwitter. RESULTS: We extracted 838,739 tweets mentioning at least 1 contraceptive method. The annual number of contraception-related tweets increased considerably over the study period. The intrauterine device was the most commonly referenced method (45.9%). Long-acting methods were mentioned more often than short-acting ones (58% vs 42%), and the annual proportion of long-acting reversible contraception-related tweets increased over time. In sentiment analysis of tweets mentioning a single contraceptive method (n=665,064), the greatest proportion of all tweets was negative (65,339 of 160,713 tweets with at least 95% confident sentiment, or 40.66%). Tweets mentioning long-acting methods were nearly twice as likely to be positive compared with tweets mentioning short-acting methods (19.65% vs 10.21%; P<.002). CONCLUSION: Recognizing the influence of social networks on contraceptive decision making, social media platforms may be useful in the collection and dissemination of information about contraception.

Body mass index and B-lines on lung ultrasonography in chronic and acute heart failure.

AIMS: Increased body mass index (BMI) is common in heart failure (HF) patients and is associated with lower levels of N-terminal pro-brain natriuretic peptide (NT-proBNP). We evaluated the influence of BMI on lung ultrasonography (LUS) findings indicative of pulmonary congestion (i.e. B-lines) in patients with chronic and acute HF (AHF). METHODS AND RESULTS: We analysed ambulatory chronic HF (n = 118) and hospitalized AHF (n = 177) patients (mean age 70 years, 64% men, mean BMI 29 kg/m2 , mean ejection fraction 42%) undergoing echocardiography and LUS in eight chest zones. B-lines and chest wall thickness (skin to pleura) on ultrasound were quantified offline and blinded to clinical findings. NT-proBNP was available in AHF patients (n = 167). In chronic HF, B-line number decreased by 18% per 5 unit increase in BMI [95% confidence interval (CI) -35% to +5%, P = 0.11]. In AHF, the number of B-lines decreased by 12% per 5 unit increase in BMI (95% CI -19% to -5%, P = 0.001), whereas NT-proBNP concentration decreased by 28% per 5 unit increase in BMI (95% CI -40% to -16%, P < 0.001). For AHF, B-line number declined to a lesser degree than NT-proBNP concentration with increasing BMI (P = 0.020), and >6 B-lines were observed in half of AHF patients with severe obesity. There was an inverse relationship between B-line number and chest wall thickness, and this association varied by chest region. CONCLUSIONS: Despite an inverse relationship between B-lines and BMI, B-lines declined to a lesser degree than NT-proBNP with increasing BMI. These data suggest that LUS may be useful in patients with HF despite obesity.

Quantification of pleural effusions on thoracic ultrasound in acute heart failure.

BACKGROUND: Although pleural effusions are common among patients with acute heart failure, the relevance of pleural effusion size assessed on thoracic ultrasound has not been investigated systematically. METHODS: In this prospective observational study, we included patients hospitalised for acute heart failure and performed a thoracic ultrasound early after admission (thoracic ultrasound 1) and at discharge (thoracic ultrasound 2) independently of routine clinical management. A semiquantitative score was applied offline blinded to clinical findings to categorise and monitor pleural effusion size. RESULTS: Among 188 patients (median age 72 years, 62% men, 78% white, median left ventricular ejection fraction 38%), pleural effusions on thoracic ultrasound 1 were present in 66% of patients and decreased in size during the hospitalisation in 75% based on the pleural effusion score (P<0.0001). Higher values of the pleural effusion score were associated with higher pleural effusion volumes on computed tomography (P<0.001), higher NT-pro brain natriuretic peptide values (P=0.001) and a greater number of B-lines on lung ultrasound (P=0.004). Nevertheless, 47% of patients were discharged with persistent pleural effusions, 19% with large effusions. However, higher values of the pleural effusion score on thoracic ultrasound 2 did not identify patients at increased risk of 90-day heart failure rehospitalisations or death (adjusted hazard ratio (HR) 1.05, 95% confidence interval (CI) 0.92-1.19; P=0.46) whereas seven or more B-lines on lung ultrasound at discharge were independently associated with adverse events (adjusted HR 2.43, 95% CI 1.11-5.37; P=0.027). CONCLUSION: Among patients with acute heart failure, pleural effusions are associated with other clinical, imaging and laboratory markers of congestion and improve with heart failure therapy. The prognostic relevance of persistent pleural effusions at discharge should be investigated in larger studies.

Lung Ultrasound in Acute Heart Failure: Prevalence of Pulmonary Congestion and Short- and Long-Term Outcomes.

OBJECTIVES: This study sought to assess the prevalence, changes in, and prognostic importance of B-lines, a pulmonary congestion measure by using a simplified lung ultrasonography (LUS) method in acute heart failure (AHF). BACKGROUND: Pulmonary congestion is an important finding in AHF, but conventional methods for its detection are insensitive. METHODS: In a 2-site, prospective, observational study, 4-zone LUS was performed early during hospitalization for AHF (LUS1) and at discharge (LUS2). B-lines were quantified off-line, blinded to clinical findings and outcomes, by a core laboratory. RESULTS: Among 349 patients (median, 75 years of age; 59% men; mean ejection fraction 39%), the sum of B-lines in 4 zones ranged from 0 to 18 (LUS1). The risk of an adverse in-hospital event increased with rising number of B-lines on LUS1: the odds ratio for each B-line tertile was 1.82 (95% confidence interval [CI]: 1.14 to 2.88; p = 0.011). B-line count decreased from a median of 6 (LUS1) to 4 (LUS2; p < 0.001) over 6 days (median). In 132 patients with LUS2 images, the risk of HF hospitalization or all-cause death was greater in patients with a higher number of B-lines at discharge. This relationship was stronger closer to discharge: unadjusted hazard ratio (HR) at 60 days was 3.30 (95% CI: 1.52 to 7.17; p = 0.002); 2.94 at 90 days (95% CI: 1.46 to 5.93; p = 0.003); and 2.01 at 180 days (95% CI: 1.11 to 3.64; p = 0.021). The association between number of B-lines and short- and long-term outcomes persisted after adjusting for important clinical variables, including N-terminal pro-B-type natriuretic peptide. CONCLUSIONS: Pulmonary congestion using a simplified 4-zone LUS method was common in patients with AHF and improved with therapy. A higher number of B-lines at baseline and discharge identified patients at increased risk for adverse events.

Right atrial structure and function in patients with hypertension and with chronic heart failure.

BACKGROUND: Prior studies have shown that both heart failure (HF) and atrial fibrillation (AF) are factors that impact left atrial function and structure. However, right atrial (RA) function measured as RA emptying fraction (RAEF) on echocardiography has not been analyzed systematically in a chronic HF population. The aim of this study was to assess RA volume index (RAVI) and RAEF in patients with chronic HF and patients with hypertension (HTN) and to relate these findings to other cardiopulmonary ultrasound parameters and 12-month outcomes. METHODS AND RESULTS: In this prospective observational study, we identified 119 patients with chronic HF (64 patients without a history of AF [HF without AF], 55 with AF [HF with AF]), and 127 patients with HTN but without important cardiac disease who underwent routine outpatient transthoracic echocardiography. We found that RAEF was impaired in patients with HF without AF compared to patients with HTN (35% ±2 vs 50% ±1, P < .001), whereas RAVI did not differ between these two groups. Lower RAEF was associated with larger RAVI and higher estimated RA pressures but not with a higher degree of pulmonary congestion by lung ultrasound. Both lower RAEF and higher RAVI were associated with an increased risk of 12-month HF hospitalizations or all-cause death (age, sex, and AF adjusted HR: 4.07, 95% CI: 1.69-9.79; P = .002, vs 2.74, 95% CI: 1.15-6.54, P = .023). CONCLUSIONS: In an outpatient HF cohort, both lower RAEF and increased RAVI were associated with other markers of impaired cardiac function and 12-month adverse events.

Pulmonary Congestion by Lung Ultrasound in Ambulatory Patients With Heart Failure With Reduced or Preserved Ejection Fraction and Hypertension.

BACKGROUND: Although pulmonary congestion can be quantified in heart failure (HF) by means of lung ultrasonography (LUS), little is known about LUS findings (B-lines) in different HF phenotypes. This prospective cohort study investigated the prevalence and clinical and echocardiographic correlates of B-lines in ambulatory HF patients with preserved (HFpEF) or reduced (HFrEF) ejection fraction compared with hypertensive patients. We related LUS findings to 12-month HF hospitalizations and all-cause mortality. METHODS AND RESULTS: We used LUS to examine hypertensive (n = 111), HFpEF (n = 46), and HFrEF (n = 73) patients (median age 66 y, 56% male, 79% white, and median EF 55%) undergoing clinically indicated outpatient echocardiography. B-line number was quantified offline, across 8 chest zones, blinded to clinical and echocardiographic characteristics. The proportion of patients with ≥3 B-lines was lower in hypertensive patients (13.5%) compared with both HFrEF (45.2%, P < .001) and HFpEF (34.8%; P = .05). HF patients with ≥3 B-lines had a higher risk of the composite outcome (age- and sex-adjusted hazard ratio 2.62, 95% confidence interval 1.15-5.96; P = .022). CONCLUSIONS: When performed at the time of outpatient echocardiography, LUS findings of pulmonary congestion differ between patients with known HF and those with hypertension, and may be associated with adverse outcomes.

Dynamic changes and prognostic value of pulmonary congestion by lung ultrasound in acute and chronic heart failure: a systematic review.

AIMS: Pulmonary congestion is an important finding in patients with heart failure (HF) that can be quantified by lung ultrasound (LUS). We conducted a systematic review to describe dynamic changes in LUS findings of pulmonary congestion (B-lines) in HF and to examine the prognostic utility of B-lines in HF. METHODS AND RESULTS: We searched online databases for studies conducted in patients with chronic or acute HF that used LUS to assess dynamic changes or the prognostic value of pulmonary congestion. We included studies in adult populations, published in English, and conducted in ≥25 patients. Of 1327 identified studies, 13 (25-290 patients) met the inclusion criteria: six reported on dynamic changes in LUS findings (438 patients) and seven on the prognostic value of B-lines in HF (953 patients). In acute HF, B-line number changed within as few as 3 h of HF treatment. In acute HF, ≥15 B-lines on 28-zone LUS at discharge identified patients at a more than five-fold risk for HF readmission or death. Similarly, in ambulatory patients with chronic HF, ≥3 B-lines on five- or eight-zone LUS marked those at a nearly four-fold risk for 6-month HF hospitalization or death. CONCLUSIONS: Lung ultrasound findings change rapidly in response to HF therapy. This technique may represent a useful and non-invasive method to track dynamic changes in pulmonary congestion. Furthermore, residual congestion at the time of discharge in acute HF or in ambulatory patients with chronic HF may identify those at high risk for adverse events.

Relations Between Aortic Stiffness and Left Ventricular Mechanical Function in the Community.

BACKGROUND: Aortic stiffness impairs optimal ventricular-vascular coupling and left ventricular systolic function, particularly in the long axis. Left ventricular global longitudinal strain (GLS) has recently emerged as a sensitive measure of early cardiac dysfunction. In this study, we investigated the relation between aortic stiffness and GLS in a large community-based sample. METHODS AND RESULTS: In 2495 participants (age 39-90 years, 57% women) of the Framingham Offspring and Omni cohorts, free of cardiovascular disease, we performed tonometry to measure arterial hemodynamics and echocardiography to assess cardiac function. Aortic stiffness was evaluated as carotid-femoral pulse wave velocity and as characteristic impedance, and GLS was calculated using speckle tracking-based measurements. In multivariable analyses adjusting for age, sex, height, systolic blood pressure, augmentation index, left ventricular structure, and additional cardiovascular risk factors, increased carotid-femoral pulse wave velocity (B±SE: 0.122±0.030% strain per SD, P<0.0001) and characteristic impedance (0.090±0.029, P=0.002) were both associated with worse GLS. We observed effect modification by sex on the relation between characteristic impedance and GLS (P=0.004); in sex-stratified multivariable analyses, the relation between greater characteristic impedance and worse GLS persisted in women (0.145±0.039, P=0.0003) but not in men (P=0.73). CONCLUSIONS: Multiple measures of increased aortic stiffness were cross-sectionally associated with worse GLS after adjusting for hemodynamic variables. Parallel reductions in left ventricular long axis shortening and proximal aortic longitudinal strain in individuals with a stiffened proximal aorta, from direct mechanical ventricular-vascular coupling, offers an alternative explanation for the observed relations.

Sex differences in cardiovascular ageing.

Despite recent progress in identifying and narrowing the gaps in cardiovascular outcomes between men and women, general understanding of how and why cardiovascular disease presentations differ between the sexes remains limited. Sex-specific patterns of cardiac and vascular ageing play an important role and, in fact, begin very early in life. Differences between the sexes in patterns of age-related cardiac remodelling are associated with the relatively greater prevalence in women than in men of heart failure with preserved ejection fraction. Similarly, sex variation in how vascular structure and function change with ageing contributes to differences between men and women in how coronary artery disease manifests typically or atypically over the adult life course. Both hormonal and non-hormonal factors underlie sex differences in cardiovascular ageing and the development of age-related disease. The midlife withdrawal of endogenous oestrogen appears to augment the age-related increase in cardiovascular risk seen in postmenopausal compared with premenopausal women. However, when compared with intrinsic biological differences between men and women that are present throughout life, this menopausal transition may not be as substantial an actor in determining cardiovascular outcomes.

Detection and prognostic value of pulmonary congestion by lung ultrasound in ambulatory heart failure patients.

AIMS: Pulmonary congestion is a common and important finding in heart failure (HF). While clinical examination and chest radiography are insensitive, lung ultrasound (LUS) is a novel technique that may detect and quantify subclinical pulmonary congestion. We sought to independently relate LUS and clinical findings to 6-month HF hospitalizations and all-cause mortality (composite primary outcome). METHODS: We used LUS to examine 195 NYHA class II-IV HF patients (median age 66, 61% men, 74% white, ejection fraction 34%) during routine cardiology outpatient visits. Lung ultrasound was performed in eight chest zones with a pocket ultrasound device (median exam duration 2 min) and analysed offline. RESULTS: In 185 patients with adequate LUS images in all zones, the sum of B-lines (vertical lines on LUS) ranged from 0 to 13. B-lines, analysed by tertiles, were associated with clinical and laboratory markers of congestion. Thirty-two per cent of patients demonstrated ≥3 B-lines on LUS, yet 81% of these patients had no findings on auscultation. During the follow-up period, 50 patients (27%) were hospitalized for HF or died. Patients in the third tertile (≥3 B-lines) had a four-fold higher risk of the primary outcome (adjusted HR 4.08, 95% confidence interval, CI 1.95, 8.54; P < 0.001) compared with those in the first tertile and spent a significantly lower number of days alive and out of the hospital (125 days vs. 165 days; adjusted P < 0.001). CONCLUSIONS: Pulmonary congestion assessed by ultrasound is prevalent in ambulatory patients with chronic HF, is associated with other features of clinical congestion, and identifies those who have worse prognosis.

Distinct Aspects of Left Ventricular Mechanical Function Are Differentially Associated With Cardiovascular Outcomes and All-Cause Mortality in the Community.

BACKGROUND: There are few data relating novel measures of left ventricular (LV) mechanical function to cardiovascular disease (CVD) outcomes in the community. Whether distinct components of LV mechanical function provide information regarding risk for different CVD outcomes is unclear. METHODS AND RESULTS: We used speckle tracking echocardiography to quantify distinct components of LV mechanical function (measured as LV strain in multiple planes) in 2831 Framingham Offspring Study participants (mean age, 66 years; 57% women, 97% with LV fractional shortening >0.29). Participants were followed for 6.0±1.2 years for onset of 69 coronary heart disease (CHD), 71 heart failure (HF), and 199 mortality events. Adjusting for CVD risk factors, longitudinal LV strain appeared associated with incident CHD (hazards ratio [HR] per SD increment, 1.29; 95% confidence interval [CI], 1.00-1.67; P=0.05), whereas circumferential and radial strain were not (P>0.37 for both); however, the association of longitudinal strain with CHD was nonsignificant after Bonferroni correction. By contrast, circumferential strain was a significant predictor of incident HF (HR per SD increment, 1.79; 95% CI, 1.35-2.37; P<0.0001). Decrements in circumferential, radial, and longitudinal strain measures were related to all-cause mortality (P<0.008 for all). Results remained similar in multivariable models adjusting additionally for the conventional echocardiographic measures of LV mass and fractional shortening. CONCLUSIONS: In our large, community-based sample, distinct components of LV mechanical function were associated with specific CVD outcomes. Additional studies are needed to replicate these findings and investigate the prognostic and therapeutic utility of these novel measures of LV mechanical function.

Impact of device selection and clip duration on lung ultrasound assessment in patients with heart failure.

OBJECTIVES: Pulmonary edema is a common sign of heart failure and can be quantified by counting vertical artifacts (B-lines) on lung ultrasound (LUS). The primary aim of this study was to compare a pocket size ultrasound device to high-end ultrasound systems on the measured number of B-lines. We also compared the impact of different-length ultrasound clips on the measured number of B-lines. METHODS AND RESULTS: We studied 21 hospitalized patients with heart failure (81% men; median age, 73; 71% Caucasian) who underwent concurrent 8- and 4-zone LUS using both a pocket ultrasound device and a high-end ultrasound system. For the 4-zone scanning method, the median B line number was 2 (interquartile range, 1-4) for the pocket device and 3 (1-5) for the high-end system (P = .67). For the 8-zone method, the median B-line number was 4 (2-7) for the pocket device and 5 (3-7) for the high-end system (P = .18). A higher number of B-lines was identified on the 4- vs 2-second LUS clips (P < .001 for 4 zones, P = .001 for 8 zones), and on the 6- vs 4-second LUS clips (P=0.057 for 4 zones, P=0.018 for 8 zones). CONCLUSIONS: Our findings suggest significant differences based on LUS clip duration rather than the type of ultrasound device used, with respect to the number of B-lines detectable in patients with heart failure. These factors should be considered in the design and reporting of LUS studies and in longitudinal assessments of heart failure patients.

Haeme oxygenase signalling pathway: implications for cardiovascular disease.

Evidence now points to the haeme oxygenase (HO) pathway as a possible actor in modulating risk for cardiovascular disease (CVD). In particular, the HO pathway may represent a key endogenous modulator of oxidative, inflammatory, and cytotoxic stress while also exhibiting vasoregulatory properties. In this review, we summarize the accumulating experimental and emerging clinical data indicating how activity of the HO pathway and its products may play a role in mechanisms underlying the development of CVD. We also identify gaps in the literature to date and suggest future directions for investigation. Because HO pathway activity can be influenced not only by genetic traits and environmental stimuli but also by a variety of existing pharmacologic interventions, the pathway could serve as a prime target for reducing the overall burden of CVD. Further work is needed to determine the role of HO pathway products as possible prognostic markers of risk for clinical CVD events and the extent to which therapeutic augmentation or inhibition of HO pathway activity could serve to modify CVD risk.

Pegylated siRNA-loaded calcium phosphate nanoparticle-driven amplification of cancer cell internalization in vivo.

The cell membrane is a critical barrier to effective delivery for many therapeutics, including those which are nanoparticle-based. Improving nanoparticle transport across the cell membrane remains a fundamental challenge. Cancer cells preferentially internalized pegylated calcium phosphate nanoparticles over normal epithelial cells. Furthermore, non-cytotoxic levels of doxorubicin markedly amplified this difference by increasing free unbound caveolin-1 and resulted in enhanced caveolin-mediated nanoparticle endocytosis in cancer cells. Engineered pegylated siRNA-loaded triple-shell calcium phosphate nanoconstructs incorporating ultra-low levels of doxorubicin recapitulated these effects and delivered increased numbers of siRNA into cancer cells with target-specific results. Systemic administration of nanoparticles in vivo demonstrated highly preferential entry into tumors, little bystander organ biodistribution, and significant tumor growth arrest. In conclusion, siRNA-loaded calcium phosphate nanoparticles incorporating non-cytotoxic amounts of doxorubicin markedly enhances nanoparticle internalization and results in increased payload delivery with concomitant on-target effects.