Randomized Trial of Information for Older Women About Cessation of Breast Cancer Screening Invitations.

BACKGROUND: Older women receive no information about why Australia's breast screening program (BreastScreen) invitations cease after 74 years. We tested how providing older women with the rationale for breast screening cessation impacted informed choice (adequate knowledge; screening attitudes aligned with intention). METHODS: In a three-arm online randomized trial, eligible participants were females aged 70-74 years who had recently participated in breast screening (within 5 years), without personal breast cancer history, recruited through Qualtrics. Participants read a hypothetical scenario in which they received a BreastScreen letter reporting no abnormalities on their mammogram. They were randomized to receive the letter: (1) without any rationale for screening cessation (control); (2) with screening cessation rationale in printed-text form (e.g., downsides of screening outweigh the benefits after age 74); or (3) with screening cessation rationale presented in an animation video form. The primary outcome was informed choice about continuing/stopping breast screening beyond 74 years. RESULTS: A total of 376 participant responses were analyzed. Compared to controls (n = 122), intervention arm participants (text [n = 132] or animation [n = 122]) were more likely to make an informed choice (control 18.0%; text 32.6%, p = .010; animation 40.5%, p < .001). Intervention arm participants had more adequate knowledge (control 23.8%; text 59.8%, p < .001; animation 68.9%, p < .001), lower screening intentions (control 17.2%; text 36.4%, p < .001; animation 49.2%, p < .001), and fewer positive screening attitudes regarding screening for themselves in the animation arm, but not in the text arm (control 65.6%; text 51.5%, p = .023; animation 40.2%, p < .001). CONCLUSIONS: Providing information to older women about the rationale for breast cancer screening cessation increased informed decision-making in a hypothetical scenario. This study is an important first step in improving messaging provided by national cancer screening providers direct to older adults. Further research is needed to assess the impact of different elements of the intervention and the impact of providing this information in clinical practice, with more diverse samples. TRIAL REGISTRATION: ANZCTRN12623000033640.

Do healthcare providers consider the social determinants of health? Results from a nationwide cross-sectional study in the United States.

BACKGROUND: While the social determinants of health (SDOH) have a greater impact on individual health outcomes than the healthcare services a person receives, healthcare providers face barriers to addressing these factors in clinical settings. Previous studies have shown that providers often lack the necessary knowledge and resources to adequately screen for and otherwise assist patients with unmet social needs. This study explores the perceptions and behaviors related to SDOH among healthcare providers in the United States (US). METHODS: This cross-sectional study analyzed data from a 22-item online survey using Reaction Data's research platform of healthcare professionals in the US. Survey items included demographic questions as well as Likert scale questions about healthcare providers' perceptions and behaviors related to SDOH. Descriptive statistics were calculated, and further analyses were conducted using t-tests and analysis of variance. RESULTS: A total of 563 respondents completed the survey, with the majority being male (72.6%), White (81%), and located in urban areas (82.2%). In terms of perceptions, most providers agreed or strongly agreed that SDOH affect the health outcomes of all patients (68.5%), while only 24.1% agreed or strongly agreed that their healthcare setting was set up to address SDOH. In terms of behavior, fewer than half currently screened for SDOH (48.6%) or addressed (42.7%) SDOH in other ways. Most providers (55.7%) wanted additional resources to focus on SDOH. Statistical analyses showed significant differences by gender, with females being more likely than males to prioritize SDOH, and by specialty, with psychiatrists, pediatricians, and family/general medicine practitioners being more likely to prioritize SDOH. CONCLUSION: Most healthcare providers understand the connection between unmet social needs and their patients' health, but they also feel limited in their ability to address these issues. Ongoing efforts to improve medical education and shift the healthcare system to allow for payment and delivery of more holistic care that considers SDOH will likely provide new opportunities for healthcare providers. In addition to what they can do at the institutional and patient levels, providers have the potential to advocate for policy and system changes at the societal level that can better address the root causes of social issues.

Prior trauma experiences among state patients charged with murder: A retrospective records review.

Background: Trauma experiences, particularly in childhood, have been associated with criminality and mental illness. There is a paucity of research into the crime of murder, trauma and mental illness. Aim: This research study focused on state patients charged with murder and sought to determine associations with prior trauma experiences, and specific types of traumas (sexual, physical and emotional). Setting: The study was conducted at a forensic psychiatric hospital in Johannesburg, South Africa. Methods: The records of state patients admitted over a 21-year period on a charge of murder were reviewed and analysed with respect to sociodemographic variables, clinical profiles, trauma experience and victim characteristics. Results: Experience of trauma in this population, with a much higher number of males compared with females, was lower than previous studies. Neurocognitive disorder was significantly associated with physical trauma. Physical trauma was found to have a significantly negative association with psychotic disorders, compared with other mental disorders. Conclusion: Although trauma is common in psychiatric patients, the study's findings are lower than previous studies. Noting the male bias in state patients that commit murder, greater sample sizes are needed to adequately address issues of specific types of traumas, the development of mental illness and murder. Contribution: Exploring and managing prior trauma in state patients who commit murder is important while considering rehabilitation efforts, such that reintegration into the community and non-recidivism are encouraged.

Factors Influencing Primary Care Practitioners' Cancer Screening Recommendations for Older Adults: a Systematic Review.

BACKGROUND: Primary care practitioners (PCPs) play a key role in cancer screening decisions for older adults (≥ 65 years), but recommendations vary by cancer type and jurisdiction. PURPOSE: To examine the factors influencing PCPs' recommendations for breast, cervical, prostate, and colorectal cancer screening for older adults. DATA SOURCES: MEDLINE, Pre-Medline, EMBASE, PsycINFO, and CINAHL, searched from 1 January 2000 to July 2021, and citation searching in July 2022. STUDY SELECTION: Assessed factors influencing PCPs' breast, prostate, colorectal, or cervical cancer screening decisions for older adults' (defined either as ≥ 65 years or < 10-year life expectancy). DATA EXTRACTION: Two authors independently conducted data extraction and quality appraisal. Decisions were crosschecked and discussed where necessary. DATA SYNTHESIS: From 1926 records, 30 studies met inclusion criteria. Twenty were quantitative, nine were qualitative, and one used a mixed method design. Twenty-nine were conducted in the USA, and one in the UK. Factors were synthesized into six categories: patient demographic characteristics, patient health characteristics, patient and clinician psycho-social factors, clinician characteristics, and health system factors. Patient preference was most reported as influential across both quantitative and qualitative studies. Age, health status, and life expectancy were also commonly influential, but PCPs held nuanced views about life expectancy. Weighing benefits/harms was also commonly reported with variation across cancer screening types. Other factors included patient screening history, clinician attitudes/personal experiences, patient/provider relationship, guidelines, reminders, and time. LIMITATIONS: We could not conduct a meta-analysis due to variability in study designs and measurement. The vast majority of included studies were conducted in the USA. CONCLUSIONS: Although PCPs play a role in individualizing cancer screening for older adults, multi-level interventions are needed to improve these decisions. Decision support should continue to be developed and implemented to support informed choice for older adults and assist PCPs to consistently provide evidence-based recommendations. REGISTRATION: PROSPERO CRD42021268219. FUNDING SOURCE: NHMRC APP1113532.

Frequency and outcomes of STEMI patients presenting between 12 and 24 h after symptom onset: Late-presenting STEMI.

OBJECTIVES: To assess the characteristics and prognosis of ST-elevation myocardial infarction (STEMI) patients, presenting between 12 and 24 h after symptom onset, in contemporary regional STEMI systems of care in the United States. BACKGROUND: Previous observational studies have been inconsistent regarding the benefit of primary percutaneous coronary intervention (PCI) compared with conservative management for late-presenting STEMI patients and the majority of randomized trials are from the fibrinolytic era. METHODS: Using a two-center registry-based cohort from March 2003 to December 2020, we evaluated the frequency, clinical characteristics, and outcomes of STEMI patients, stratified by symptom onset to balloon time: <3, 3-6, 6-12, and 12-24 h (late presenters). RESULTS: Among 5427 STEMI patients with available symptom onset time, 6.2% were late presenters, which increased to 11% during the early phase of the Covid-19 pandemic. As symptom onset to balloon time increased, patients were more likely to be older, female, and have a history of hypertension and diabetes mellitus. Late presenters with an identifiable culprit lesion were less likely to be revascularized with PCI (96%, 96%, 95%, and 92%; p for trend = 0.004) and had a longer median door-to-balloon time (82, 109, 107, and 117 min; p for trend < 0.001). In-hospital and 1-year death risks were comparable between late and earlier presenters. CONCLUSION: Despite the unfavorable risk profile and longer door-to-balloon time, clinical outcomes of late presenters were similar to those presenting within 12 h of symptom onset.

Screening for cancer beyond recommended upper age limits: views and experiences of older people.

BACKGROUND: Internationally, screening programmes and clinical practice guidelines recommend when older adults should stop cancer screening using upper age limits, but it is unknown how older adults view these recommendations. OBJECTIVE: To examine older adults' views and experiences about continuing or stopping cancer screening beyond the recommended upper age limit for breast, cervical, prostate and bowel cancer. DESIGN: Qualitative, semi-structured interviews. SETTING: Australia, telephone. SUBJECTS: A total of 29 community-dwelling older adults (≥70-years); recruited from organisation newsletters, mailing lists and Facebook advertisements. METHODS: Interviews were audio-recorded, transcribed and analysed thematically using Framework Analysis. RESULTS: Firstly, older adults were on a spectrum between trusting recommendations and actively deciding about cancer screening, with some who were uncertain. Secondly, participants reported limited in-depth discussions with health professionals about cancer screening. In primary care, discussions were focused on checking they were up to date with screening or going over results. Discussions mostly only occurred if older adults initiated themselves. Finally, participants had a socially- and self-constructed understanding of screening recommendations and potential outcomes. Perceived reasons for upper age limits were cost, reduced cancer risk or ageism. Risks of screening were understood in relation to their own social experiences (e.g. shared stories about friends with adverse outcomes of cancer treatment or conversations with friends/family about controversy around prostate screening). CONCLUSIONS: Direct-to-patient information and clinician support may help improve communication about the changing benefit to harm ratio of cancer screening with increasing age and increase understanding about the rationale for an upper age limit for cancer screening programmes.

Impact of alternative terminology for depression on help-seeking intention: A randomized online trial.

OBJECTIVE: People with depression experience barriers to seeking professional help. Different diagnostic terminology can influence people's treatment/management preferences. The aim of this study was to investigate how alternative depression diagnostic labels and recommendations impact help-seeking intentions and psychosocial outcomes. METHODS: Participants (18-70 years) were recruited using an online panel (Australia) to complete a randomized controlled trial. They read a hypothetical scenario where they discussed experiencing depressive symptoms with their GP and were randomized to receive one of four diagnoses ("depression," "burnout," "functional impairment syndrome" [fictitious label], no label [control]), and one of two follow-up recommendations ("clinical psychologist," "mind coach"). PRIMARY OUTCOME: help-seeking intention (5-point scale, higher = greater intention); secondary outcomes: intention to speak to boss, self-stigma, worry, perceived severity, illness perceptions, and personal stigma. RESULTS: A total of 676 participants completed the survey. There was no main effect of diagnostic label on help-seeking intention or stigma outcomes. Intention to speak to a boss was higher with the depression compared to burnout label (MD = 0.40, 95% CI: 0.14-0.66) and perceived severity was higher with the depression label compared to control (MD = 0.48, 95% CI: 0.22-0.74) and all other labels. Those who received the "clinical psychologist" recommendation reported higher help-seeking intention (MD = 0.43, 95% CI: 0.25-0.60) and treatment control (MD = 0.69, 95% CI: 0.29-1.10) compared to the "mind coach" recommendation. CONCLUSION: Findings highlight the success of efforts to promote help-seeking from clinical psychologists for depression. If burnout is considered a separate diagnostic entity to depression, greater awareness around what such a diagnosis means may be needed. Future research should examine how different terminologies surrounding other mental health conditions impact help-seeking and stigma.

Impact of a multidisciplinary acute aortic dissection program: Improved outcomes with a comprehensive initial surgical repair strategy.

OBJECTIVE: As part of a multidisciplinary aortic dissection (AD) program, a more comprehensive repair strategy for patients with acute type A aortic dissection (ATAAD) and frequent endografting for suitable patients with type B aortic dissection (ATBAD) was adopted in 2015. The aim of this study was to evaluate the impact of these changes. METHODS: This study is a retrospective review of a prospective database containing all patients treated for acute AD between 2003 and 2020. Patients were grouped based on differing repair strategies (pre 2015 vs post 2015). Clinical characteristics, procedural details, and survival data were analyzed. RESULTS: During this time, 323 patients (210 pre, 113 post) were treated for acute AD at our institution. There were 221 patients with ATAAD (149 pre, 72 post) and 102 patients with ATBAD (61 pre, 41 post). The majority (60%) were males, with a mean age of 65.9 ± 15.2 years. There were no differences in cardiovascular risk factors or demographics between the groups. After 2015, fewer patients with ATAAD underwent medical management alone (15% pre vs 4% post; P = .014), and most that underwent surgical intervention had a total arch or aggressive hemiarch repair (27% pre vs 78% post; P < .001). Seventy-four patients (73%) with ATBAD were treated medically, whereas 28 underwent medical management and endografting (23% pre, 34% post; P = .214). For all patients with AD, 30-day mortality was significantly improved (26% pre vs 10% post; P < .001) especially among patients who underwent ATAAD surgery (23% pre vs 9% post; P = .018). Three-year Kaplan-Meier survival estimates showed survival improvement among patients with ATAAD (Log rank P-value = .019); however, this improvement does not extend to type B dissections or the overall cohort. A survival analysis landmarked to 30 days after initial presentation showed no statistical difference in survival from 30 days to 3 years post-presentation. CONCLUSIONS: A more comprehensive repair strategy in the management of patients with acute AD resulted in improved overall patient outcomes and significantly decreased 30-day mortality, even though more complex repairs were performed. The long-term impact of the changes made to our program remains to be evaluated.

The impact of health literacy on psychosocial and behavioural outcomes among people at low risk of cardiovascular disease.

This study aimed to explore the impact of health literacy on psychosocial and behavioural outcomes for people who were not at high risk of cardiovascular disease receiving a hypothetical blood pressure reading of 135/85 mmHg. We performed a secondary analysis of data from a national sample of Australians aged 40 to 50 years (n = 1318) recruited online. Health literacy was measured using the validated Newest Vital Sign (inadequate: 0-3; adequate: 4-6). Analysed outcomes included: willingness to increase exercise and accept medication; perceived severity; positive and negative affect; illness perceptions and impacts on life and motivation. Participants with inadequate levels of health literacy perceived a blood pressure reading of 135/85 mmHg to be less serious compared to individuals with adequate health literacy (Mean Difference [MD]:0.21; 95%CI 0.03-0.39; p = .024; d = 0.13), and reported less motivation to eat well (MD:0.44; 95%CI 0.31-0.58; p < .001; d = 0.38) and exercise (MD:0.43; 95%CI 0.31-0.58; p < .001; d = 0.36). However, they were more willing to accept medication (MD:0.20; 95%CI 0.07-0.34; p = .004; d = 0.17). Participants with inadequate health literacy also perceived the condition to have fewer negative impacts on aspects of life and work than individuals with adequate health literacy, but reported greater negative emotion and more negative illness perceptions (all p < .001). Tailored communication and behaviour change support may be needed when communicating blood pressure information to people with lower health literacy and not at high risk of cardiovascular disease given the differential impacts on medication (increased willingness) and healthy exercise and diet behaviours (decreased willingness) observed in this study.

Sex Differences in Right Ventricular Systolic Function and All-Cause Mortality in Tricuspid Regurgitation.

INTRODUCTION: Sex differences have been poorly studied in patients with right-sided heart valve disease. The principal aim of the current study was to explore the impact of sex differences on right ventricular (RV) hemodynamics and all-cause mortality in patients with moderate or severe tricuspid regurgitation (TR). METHODS: This is a retrospective study of 209 patients with significant TR. All patients were clinically profiled at baseline and underwent a transthoracic echocardiogram. The cohort was followed up for clinical events for a median duration of 80 months (mean ± SD 69.4 ± 33.4 months). RESULTS: There were 117 women with a mean (± SD) age of 72.6 ± 13 years and 92 men with a mean (± SD) age of 70.8 ± 15.8 years. There were no sex differences between the individual measures of RV systolic function (tricuspid annular plane systolic excursion [TAPSE], systolic pulmonary artery pressure, and RV S'), but overall RV systolic dysfunction (TAPSE <16 mm and/or RV S' <10 cm/s) and left ventricular ejection fraction <50% were more common in men. Mean (± SD) RV wall tension (RV WT) was 3,170 ± 1,220 mm Hg × mm in women and 3,817 ± 1,499 mm Hg × mm in men (p = 0.002). There was no difference in all-cause mortality between women and men (Log-Rank p = 0.528). Age and increased RV WT were independent predictors of all-cause mortality both in women (hazard ratio [HR] 2.61) and men (HR 3.01). CONCLUSIONS: In this cohort of patients with significant TR, women more frequently had preserved RV systolic function than men. There was no sex-difference in all-cause mortality. An increased RV WT and higher age were independent predictors of all-cause mortality in both women and men.

General practitioners' views and experiences of communicating with older people about cancer screening: a qualitative study.

BACKGROUND: Older adults should be supported to make informed decisions about cancer screening. However, it is unknown how general practitioners (GPs) in Australia communicate about cancer screening with older people. AIM: To investigate GPs' views and experiences of communicating about cancer screening (breast, cervical, prostate, and bowel) with older people (≥70 years). DESIGN AND SETTING: Qualitative, semi-structured interviews, Australia. METHOD: Interviews were conducted with GPs practising in Australia (n = 28), recruited through practice-based research networks, primary health networks, social media, and email invitation. Interviews were audio-recorded and analysed thematically using Framework Analysis. RESULTS: Findings across GPs were organized into 3 themes: (i) varied motivation to initiate cancer screening discussions; some GPs reported that they only initiated screening within recommended ages (<75 years), others described initiating discussions beyond recommended ages, and some experienced older patient-initiated discussions; (ii) GPs described the role they played in providing screening information, whereby detailed discussions about the benefits/risks of prostate screening were more likely than other nationally funded screening types (breast, cervical, and bowel); however, some GPs had limited knowledge of recommendations and found it challenging to explain why screening recommendations have upper ages; (iii) GPs reported providing tailored advice and discussion based on personal patient preferences, overall health/function, risk of cancer, and previous screening. CONCLUSIONS: Strategies to support conversations between GPs and older people about the potential benefits and harms of screening in older age and rationale for upper age limits to screening programmes may be helpful. Further research in this area is needed.

Does personalised nutrition advice based on apolipoprotein E and methylenetetrahydrofolate reductase genotype affect dietary behaviour?

Background: Dietary intake is linked to numerous modifiable risk factors of cardiovascular disease. Current dietary recommendations in the UK to reduce the risk of cardiovascular disease are not being met. A genotype-based personalised approach to dietary recommendations may motivate individuals to make positive changes in their dietary behaviour. Aim: To determine the effect of a personalised nutrition intervention, based on apolipoprotein E (ApoE, rs7412; rs429358) and methylenetetrahydrofolate reductase (MTHFR, rs1801133) genotype, on reported dietary intake of saturated fat and folate in participants informed of a risk genotype compared to those informed of non-risk genotype. Methods: Baseline data (n = 99) were collected to determine genotype (non-risk vs risk), dietary intake and cardiovascular risk (Q-Risk®2 cardiovascular risk calculator). Participants were provided with personalised nutrition advice via email based on their ApoE and MTHFR genotype and reported intake of folate and saturated fat. After 10 days, dietary intake data were reported for a second time. Results: Personalised nutrition advice led to favourable dietary changes, irrespective of genotype, in participants who were not meeting dietary recommendations at baseline for saturated fat (p < 0.001) and folate (p = 0.002). Only participants who were informed of a risk ApoE genotype met saturated fat recommendations following personalised nutrition advice. Conclusion: Incorporation of genotype-based personalised nutrition advice in a diet behaviour intervention may elicit favourable changes in dietary behaviour in participants informed of a risk genotype. Participants informed of a non-risk genotype also respond to personalised nutrition advice favourably but to a lesser extent.

Technical approach, outcomes, and exposure-related complications in patients undergoing anterior lumbar interbody fusion.

OBJECTIVE: To describe our technique, evaluate access related complications and factors contributing to adverse outcomes in patients undergoing retroperitoneal anterior lumbar interbody fusion (ALIF). METHODS: We conducted a retrospective analysis of prospectively collected data on patients undergoing ALIF at our institution from January 2008 to December 2017. Access was performed by a vascular surgeon who remained present for the duration of the case. Data collected included patients' demographics, comorbidities, exposure related complications and ileus. Study end points included major adverse events and minor complications. Major adverse events included any vascular injuries requiring repair, bowel and ureter injuries, postoperative bleeding requiring reoperation, myocardial infarction, stroke, venous thromboembolism (pulmonary embolism/deep venous thrombosis), wound dehiscence, and death. Minor complications included postoperative paralytic ileus, urinary tract infections, and surgical site infections. The incidence of incisional hernia was also evaluated. RESULTS: During this period, 1178 patients (514 males and 664 females; mean age, 54.1 ± 13.8 years) underwent a total of 2352 levels ALIF at our institution (single level, 422 patients; 2 levels, 450; 3 levels, 205; 4 levels, 98; 5 levels, 6; 6 levels, 1; and 7 levels, 1). The median estimated blood loss was 25 mL (interquartile range, 25-50). There were 57 exposure-related complications (4.8%), including vascular injuries (venous, 13; arterial, 4) in 17 patients (1.4%), bowel injuries in three patients (serosa tear in two and arterial embolization with subsequent bowel ischemia in one). Eleven of the 13 venous injuries (84.6%) occurred while exposing the L4 to L5 lumbar level. Two of the four patients with arterial injuries developed acute limb ischemia requiring embolectomy. One embolized to the superior mesenteric artery and underwent bowel resection. Twenty patients (1.7%) developed venous thromboembolism, two of whom had sustained left iliac vein injury during exposure. Sixteen patients (1.4%) developed a retroperitoneal hematoma/seroma with nine requiring evacuation in the operating room. Thirty-six patients (3.1%) developed postoperative ileus, defined as an inability to tolerate diet on postoperative day 3. Four patients (0.4%) had a postoperative myocardial infarction, and two had a stroke and two (0.17%) died within the first 30 postoperative days. Thirty-one patients developed incisional complications, including surgical site infection in 24 and incisional hernia in 7. CONCLUSIONS: Our findings suggest that ALIF exposure can be performed safely with a relatively low overall complication rate. The majority of vascular injuries associated with this procedure are venous in nature, occurring predominantly while exposing the L4 to L5 level and can be safely addressed by an experienced vascular team.

The impact of donor total estimated blood volume on nucleated cell yield in bone marrow harvests for hematopoietic stem cell transplantation.

BACKGROUND: Nucleated cell yields of marrow harvests depend on factors related to donors, the procedure itself, and the volume of marrow harvested. Few attempts have been made to relate donor characteristics to harvest volume. We hypothesize that the percentage of total donor blood volume accessed for harvesting impacts the nucleated cell yield per ml of marrow collected. METHODS AND MATERIALS: We investigated 481 consecutive unrelated marrow harvests from a single center. Donor characteristics including weight, body mass index (BMI), white blood cells (WBCs), hemoglobin (Hgb), and platelet counts, as well as estimated total blood volume, were recorded and compared with nucleated cell yields and harvest volumes. RESULTS: The percentage of donor blood volume accessed for marrow harvesting was inversely related to nucleated cell yields (r = -0.57). The donor-recipient weight differential impacted cell yields as well (r = 0.35), with heavier recipients requiring increased marrow volumes from smaller donors to satisfy their nucleated cell needs. 3.73 × 108 /kg of recipient weight could be collected with 95% certainty when harvest volumes did not exceed 16.1% of donor total blood volume. In a stepwise multiple regression analysis, 45.4% of cell yield variance was explained by blood volume percentage accessed for harvesting, donor weight, and WBC. Donor sex, BMI, and platelet counts did not contribute further to cell yield variance. Smokers had higher cell yields than nonsmokers (20.4 vs. 18.3 × 106 /ml; 95% confidence interval 0.62, 3.47) independent of other parameters. CONCLUSION: Establishing the relationship between percentage of estimated donor total blood volume and recipient cell needs can facilitate donor selection for successful hematopoietic cell (HPC) transplants.

Lipid-lowering therapies in peripheral artery disease: A review.

Peripheral artery disease (PAD) is estimated to affect approximately 8.5 million individuals in the US above the age of 40, and is associated with significant morbidity, mortality, and impairment. Despite the significant adverse limb and cardiovascular (CV) outcomes seen in patients with PAD, there is typically less attention paid to risk factor modification relative to other atherosclerotic diseases such as coronary artery disease (CAD) or stroke. In the current literature, statins have been shown to reduce mortality, major adverse CV events, major adverse limb events, and improve symptomatic outcomes in patients with PAD. In addition, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are emerging as an additional lipid-lowering therapy for patients with PAD. However, despite current guideline recommendations based on growing evidence, patients with PAD are consistently undertreated with lipid-lowering therapies. We provide an extensive literature review and evidence-based recommendations for the use of statins and PCSK9 inhibitors in patients with PAD.

Risk and Management of Venous Thromboembolism in Patients with COVID-19.

BACKGROUND: One of the most pronounced and poorly understood pathological features of COVID-19 infection has been high risk for venous and arterial thromboembolic complications. An increasing number of thromboembolic events are being reported almost on a daily basis, and the medical community has struggled to predict and mitigate this risk. We aimed to review available literature on the risk and management of COVID-19 related venous thromboembolism (VTE), and provide evidence-based guidance to manage these events. METHODS: A literature review of VTE complications in patients with COVID-19 was performed, in addition to a summary of the societal guidelines and present pathways implemented at our institution for the management of both in- and outpatient COVID-19 related VTE. RESULTS: Although a significant VTE risk has been confirmed in patients with COVID-19, literature addressing best ways to mitigate this risk is lacking. Furthermore, there has been very limited guidance provided by societal guidelines to help prevent and manage VTE associated with the COVID-19 infection. In light of the available data, we advise that all patients admitted with suspected or confirmed COVID-19 receive pharmacological prophylaxis if bleeding risk is acceptable. For patients with COVID-19 who have been discharged from the emergency department or hospital, we suggest extended thromboprophylaxis (up to 39 days) as long as bleeding risk is low. CONCLUSIONS: We believe that this literature summary along with our center recommendations and algorithms provide valuable guidance to providers caring for patients with COVID-19 related VTE. More research is needed to standardize prophylaxis and management protocols for these patients.

Impact of diagnostic labels and causal explanations for weight gain on diet intentions, cognitions and emotions: An experimental online study.

Disease labels and causal explanations for certain symptoms or conditions have been found to have both positive and negative outcomes. For example, a diagnosis of polycystic ovary syndrome could conceivably motivate a person to engage in weight management, which is the recommended first line treatment. Furthermore, doctors may feel more comfortable discussing weight when linked to a medical condition. However, such a diagnosis may elicit feelings of increased anxiety, perceived severity and reduced sense of control. Mixed findings are also evident for impacts of genetic explanations on psychosocial outcomes and behaviours. Using hypothetical scenarios presented in an online survey, participants were asked to imagine that they were visiting their general practitioner due to experiencing weight gain, irregular periods, and more pimples than usual. Participants were randomised to receive different diagnostic labels ('polycystic ovary syndrome', 'weight' or no label/description) and causal explanations (genetic or environmental) for their symptoms. Primary outcomes assessed included intention to eat a healthier diet and perceived personal control of weight (average score on scale 1-7 across 3 items). Secondary outcomes included weight stigma, blameworthiness, worry, perceived severity, self-esteem, belief diet will reduce risks and menu item choice. Participants were 545 females aged 18-45 years (mean = 33 years), living in Australia, recruited through a national online recruitment panel. The sample was overweight on average (BMI = 26.5). Participants reporting a PCOS diagnosis were excluded from analyses. We found no main effects of the label or explanation on intention to eat healthier or perceived personal control of weight. For secondary outcomes, those given the genetic explanation reported higher weight stigma (range 1-7; MD = 0.27, 95%CI: 0.011,0.522), greater worry (range 1-7; MD = 0.27, 95%CI: 0.037,0.496), lower self-esteem (range 10-40; MD = 1.26, 95%CI: 0.28 to 2.24) and perceived their weight as more severe (range 1-7; MD = 0.28; 95%CI: 0.05,0.52) than those given the environmental explanation, averaged over disease label given. These findings further highlight the deleterious effects of genetic explanations on psychosocial outcomes and reinforce the need for caution when communicating the aetiology of weight-related health issues.

Incidence, Course, and Characteristics of Hydralazine-Associated Tachycardia During Phase I Postanesthesia Recovery.

PURPOSE: This study aims to characterize the development of tachycardia after intravenous hydralazine administration during Phase I recovery. DESIGN: Retrospective observational study design. METHODS: The medical records of 745 adult surgical patients who were administered hydralazine during Phase I recovery between January 1, 2010 and December 31, 2014 were electronically reviewed to characterize episodes of tachycardia. FINDINGS: Seventy patients (94.0 cases per 1,000 administrations; 95% confidence interval = 74.0 to 117.2) developed tachycardia with a median increase of 23 beats per minute (bpm; interquartile range [IQR] = 15 to 37), a maximum rate of 106 bpm (IQR = 103 to 111; range = 101 to 131), and duration of 28 minutes (IQR = 5 to 86). The median onset of tachycardia was 43 minutes (IQR = 20 to 93), with 40% occurring after the first hour. Tachycardia was associated with female sex (P < .001), younger age (P < .001), and those with lesser comorbidities (P < .009). CONCLUSIONS: A sizeable proportion of cases of tachycardia associated with hydralazine administration occurred after 1 hour, suggesting that these patients who may not tolerate a faster heart rate warrant longer duration of monitoring.

Nonsense-mediated RNA decay--a switch and dial for regulating gene expression.

Nonsense-mediated RNA decay (NMD) represents an established quality control checkpoint for gene expression that protects cells from consequences of gene mutations and errors during RNA biogenesis that lead to premature termination during translation. Characterization of NMD-sensitive transcriptomes has revealed, however, that NMD targets not only aberrant transcripts but also a broad array of mRNA isoforms expressed from many endogenous genes. NMD is thus emerging as a master regulator that drives both fine and coarse adjustments in steady-state RNA levels in the cell. Importantly, while NMD activity is subject to autoregulation as a means to maintain homeostasis, modulation of the pathway by external cues provides a means to reprogram gene expression and drive important biological processes. Finally, the unanticipated observation that transcripts predicted to lack protein-coding capacity are also sensitive to this translation-dependent surveillance mechanism implicates NMD in regulating RNA function in new and diverse ways.

Effect of Deutetrabenazine on Chorea Among Patients With Huntington Disease: A Randomized Clinical Trial.

IMPORTANCE: Deutetrabenazine is a novel molecule containing deuterium, which attenuates CYP2D6 metabolism and increases active metabolite half-lives and may therefore lead to stable systemic exposure while preserving key pharmacological activity. OBJECTIVE: To evaluate efficacy and safety of deutetrabenazine treatment to control chorea associated with Huntington disease. DESIGN, SETTING, AND PARTICIPANTS: Ninety ambulatory adults diagnosed with manifest Huntington disease and a baseline total maximal chorea score of 8 or higher (range, 0-28; lower score indicates less chorea) were enrolled from August 2013 to August 2014 and randomized to receive deutetrabenazine (n = 45) or placebo (n = 45) in a double-blind fashion at 34 Huntington Study Group sites. INTERVENTIONS: Deutetrabenazine or placebo was titrated to optimal dose level over 8 weeks and maintained for 4 weeks, followed by a 1-week washout. MAIN OUTCOMES AND MEASURES: Primary end point was the total maximal chorea score change from baseline (the average of values from the screening and day-0 visits) to maintenance therapy (the average of values from the week 9 and 12 visits) obtained by in-person visits. This study was designed to detect a 2.7-unit treatment difference in scores. The secondary end points, assessed hierarchically, were the proportion of patients who achieved treatment success on the Patient Global Impression of Change (PGIC) and on the Clinical Global Impression of Change (CGIC), the change in 36-Item Short Form- physical functioning subscale score (SF-36), and the change in the Berg Balance Test. RESULTS: Ninety patients with Huntington disease (mean age, 53.7 years; 40 women [44.4%]) were enrolled. In the deutetrabenazine group, the mean total maximal chorea scores improved from 12.1 (95% CI, 11.2-12.9) to 7.7 (95% CI, 6.5-8.9), whereas in the placebo group, scores improved from 13.2 (95% CI, 12.2-14.3) to 11.3 (95% CI, 10.0-12.5); the mean between-group difference was -2.5 units (95% CI, -3.7 to -1.3) (P < .001). Treatment success, as measured by the PGIC, occurred in 23 patients (51%) in the deutetrabenazine group vs 9 (20%) in the placebo group (P = .002). As measured by the CGIC, treatment success occurred in 19 patients (42%) in the deutetrabenazine group vs 6 (13%) in the placebo group (P = .002). In the deutetrabenazine group, the mean SF-36 physical functioning subscale scores decreased from 47.5 (95% CI, 44.3-50.8) to 47.4 (44.3-50.5), whereas in the placebo group, scores decreased from 43.2 (95% CI, 40.2-46.3) to 39.9 (95% CI, 36.2-43.6), for a treatment benefit of 4.3 (95% CI, 0.4 to 8.3) (P = .03). There was no difference between groups (mean difference of 1.0 unit; 95% CI, -0.3 to 2.3; P = .14), for improvement in the Berg Balance Test, which improved by 2.2 units (95% CI, 1.3-3.1) in the deutetrabenazine group and by 1.3 units (95% CI, 0.4-2.2) in the placebo group. Adverse event rates were similar for deutetrabenazine and placebo, including depression, anxiety, and akathisia. CONCLUSIONS AND RELEVANCE: Among patients with chorea associated with Huntington disease, the use of deutetrabenazine compared with placebo resulted in improved motor signs at 12 weeks. Further research is needed to assess the clinical importance of the effect size and to determine longer-term efficacy and safety. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01795859.