Electrocardiographic predictors of response to sacubitril/valsartan therapy in heart failure with reduced ejection fraction.

BACKGROUND: Sacubitril/valsartan (SV) is currently recommended as a first-line therapy in patients with heart failure and reduced ejection fraction (HFrEF) due to its significant clinical and prognostic benefit; however, not all patients respond to therapy and predictors of clinical response to SV remain under-studied. AIMS: To identify electrocardiographic (ECG) predictors of response to SV therapy in HFrEF patients. METHODS: A retrospective analysis of a hospital heart failure registry was undertaken. Consecutive HFrEF patients (New York Heart Association class II-III) on maximal-dose SV were studied. Response to SV was defined as ≥10% relative improvement in left ventricular ejection fraction (LVEF) at 3-months post-maximal-dose therapy. Pre-therapy ECGs were retrospectively analyzed for axes and standard wave and interval durations. Logistic regression was used to estimate odds ratios and 95% confidence intervals for associations between predictors and therapeutic response. Backward stepwise regression was employed to develop a parsimonious model. RESULTS: P-wave duration (PWD) 100-120 ms, PWD >120 ms, and QTc >460 ms were associated with response to SV on univariate analysis: OR 18.00 (4.45-122.90), 5.00 (1.47-20.42), and 3.10 (1.18-9.22), respectively. The preferred model that included the former two predictors in combination with pre-therapy creatinine, mineralocorticoid receptor antagonist use, and LVEF was highly selective (area under the ROC curve = 0.868). CONCLUSIONS: Prolongation of both PWD and QTc interval on baseline ECG in HFrEF patients is predictive of therapeutic response to maximal-dose SV therapy and may indicate early cardiac remodeling that is highly amenable to reversal.

A systematic review of interventions to improve male knowledge of fertility and fertility-related risk factors.

Male infertility is a global health concern. The effectiveness of interventions developed to improve males' knowledge of fertility regulation and fertility-related risk factors remains unclear. This systematic review aimed to synthesize and evaluate the evidence for these interventions. Four databases were searched from inception to June 2023. Eligible studies examined interventions to increase fertility knowledge among presumed fertile males aged ≥16 years of age. Conference abstracts, protocols and studies without sex-disaggregated results for males were excluded. A narrative synthesis without meta-analysis was performed. A total of 4884 records were identified. Five studies (reported in six publications), all conducted in high-income countries, were included. Two were randomized control trials, and three were experimental studies. Interventions were delivered in person by a health professional (n = 3), online and via a mobile app. All studies showed a significant improvement in knowledge of fertility or fertility-related risk factors from baseline to follow-up. The largest improvement was observed for secondary and vocational students. A moderate, long-term retainment of knowledge was observed at two-year follow-up in one study. Available evidence suggests interventions to improve males' fertility knowledge are effective, particularly for younger, less educated males.

Women's views on content and delivery methods for interventions to improve preconception health: a qualitative exploration.

Background: Systematic review evidence suggests preconception health interventions may be effective in improving a range of outcomes. However, few studies have explored women's views on potential content and delivery methods for these interventions. Methods: Participants were purposively sampled from respondents (n = 313) of a survey. Semi-structured, in-depth interviews were conducted to explore their views on seven candidate delivery methods for preconception health interventions: general practitioners (GPs), nurse practitioners, pharmacists, social media, personal texts and emails, pregnancy tests, and health education in schools. Data were analyzed using a data-driven framework analysis. Results: Twenty women were interviewed. Women wanted interventions to be easily accessible but allow them to conceal their pregnancy plans. They preferred to choose to receive preconception interventions but were receptive to health professionals raising preconception health during 'relevant' appointments such as contraceptive counseling and cervical smear tests. They wanted intervention content to provide trustworthy and positively framed information that highlights the benefits of good preconception health and avoids stigmatizing women for their weight and preconception actions. The inclusion of support for preconception mental health and the use of visual media, personalization, simple information, and interesting and unfamiliar facts were viewed favorably. Conclusion: Interventions to improve preconception health should reflect the sensitivities of pregnancy intentions, be easy to access in a way that enables discretion, and be designed to seek consent to receive the intervention. These interventions should ideally be tailored to their target populations and provide trustworthy information from reputable sources. The potential for unintended harmful effects should be explored.

Global pain levels before and during the COVID-19 pandemic.

Physical pain has trended upward globally over the last decade. Here, we explore whether the COVID-19 pandemic modified this alarming trend. We used data from 146 countries worldwide (510,247 respondents) to examine whether pain levels changed during the COVID-19 pandemic. Adjusted regressions across countries revealed that 33.3% of people were in pain in 2019, 32.8% in 2020, 32.5% in 2021, and 34.1% in 2022. The change in pain from 2019 to each of the pandemic years was not statistically significant. This suggests that, on average, there was no significant change in pain during the pandemic. However, from 2019 to 2020 there was a significant decline in pain among individuals over 55 years of age, those who were widowed, and those without children in the household. On a global scale, the COVID-19 pandemic was not associated with a significant change in pain levels. The concerning pre-pandemic elevation in global pain continued during this challenging period.

The psychological legacy of past obesity and early mortality: evidence from two longitudinal studies.

BACKGROUND: We test a novel 'weight scarring' hypothesis which suggests that past obesity is associated with impairments in current psychological well-being and this increases risk of negative physical health outcomes associated with obesity. Across two nationally representative studies, we tested whether past obesity is associated with current psychological outcomes and whether these psychological outcomes explain the association between past obesity and subsequent early mortality. METHODS: Data were from the National Health and Nutrition Examination Survey (NHANES) (n = 29,047) and the Health and Retirement Study (HRS) (n = 11,998). Past obesity was defined based on maximum lifetime weight in NHANES and the highest weight from past study waves in the HRS. Across both studies, current depressive symptoms were analysed. A set of 10 additional well-being measures were combined to produce an 'index of impaired well-being' in HRS. Subsequent all-cause mortality was examined using National Deaths Index records in NHANES and household interviews in HRS. Linear or logistic regression, Cox proportional hazard regression, and causal mediation models were used. RESULTS: We found that past obesity was associated with greater current depressive symptoms after controlling for current weight status and in analyses limited to those who were no longer classified as having obesity in NHANES (ß = 0.17; 95% CI: 0.13, 0.22) and HRS (ß = 0.20; 95% CI: 0.08, 0.31). In HRS, past obesity was also associated with a range of current negative psychological outcomes, including an index of impaired psychological well-being (ß = 0.16; 95% CI: 0.05, 0.27). Past obesity was associated with a higher risk of early mortality in both NHANES and HRS (HR = 1.31; 95% CI: 1.16, 1.48 and HR = 1.34; 95% CI: 1.20, 1.50, respectively). Depressive symptoms explained 6% (95% CI: 0.01, 0.10) and 5% (95% CI: 0.01, 0.09) of the association between past obesity and premature mortality in NHANES and HRS, respectively. Impaired psychological well-being partly mediated the association between past obesity and premature mortality by 10% (95% CI: 0.04, 0.16) in HRS. CONCLUSIONS: Our findings suggest that there may be a psychological legacy of past obesity that is associated with raised mortality risk. Ensuring people with obesity receive psychological support even after experiencing weight loss may be important.

The Challenge of Weight Stigma for Women in the Preconception Period: Workshop Recommendations for Action from the 5th European Conference on Preconception Health and Care.

Weight stigma is a well-recognised public health issue affecting many members of society including women during the preconception period. The impacts of preconception weight stigma on women are significant and may result in decreased access to and uptake of healthcare, and mental health concerns. The consequences of this weight stigma may translate to negative maternal outcomes and even intergenerational effects on the child. Eliminating weight stigma is therefore imperative. The aim of this paper is to report recommendations to reduce weight stigma for preconception women produced at a workshop with clinical and academic experts on preconception health and weight stigma at the 5th European Conference on Preconception Health and Care. The recommendations are related to two key areas: general societal recommendations prompting all people to acknowledge and adjust our attitudes towards larger-bodied people; and healthcare-specific recommendations imploring clinicians to upskill themselves to reduce weight stigma in practice. We therefore call for urgent approaches to address societal weight-stigmatising attitudes and norms related to both the general population and preconception women, while providing professional development opportunities for healthcare professionals relating to weight stigma. Eliminating weight stigma for preconception women may have positive impacts on the outcomes for mothers and children during pregnancy and beyond.

Changes in anxiety and depression during the COVID-19 pandemic in the European population: A meta-analysis of changes and associations with restriction policies.

BACKGROUND: Early studies of common mental disorders (CMDs) during the COVID-19 pandemic mainly report increases; however, more recent findings have been mixed. Also, studies assessing the effects of restriction measures on CMDs show varied results. The aim of this meta-analysis was to assess changes in levels of CMDs from pre-/early to during the pandemic and the effects of restriction policies in the European population. METHODS: We searched for studies assessing both pre-pandemic and peri-pandemic self-reported emotional distress and symptoms of depression or anxiety among nationally/regionally representative samples in Europe and collected microdata from those studies. Estimates of corona containment index were related to changes in CMDs using random-effects meta-regression. RESULTS: Our search strategy resulted in findings from 15 datasets drawn from 8 European countries being included in the meta-analysis. There was no evidence of change in the prevalence of emotional distress, anxiety, or depression from before to during the pandemic; but from early pandemic periods to later periods, there were significant decreases in emotional distress and anxiety. Increased school restrictions and social distancing were associated with small increases in self-reported emotional distress. CONCLUSIONS: Despite initial concerns of increased emotional distress and mental illness due to the COVID-19 pandemic, the results from this meta-analysis indicate that there was a decrease in emotional distress and no change in anxiety or depression in the general population in Europe. Overall, our findings support the importance of strong governance when implementing periodic and robust restriction measures to combat the spread of COVID-19.

Personalized Dual Antiplatelet Therapy in Acute Coronary Syndromes: Striking a Balance Between Bleeding and Thrombosis.

PURPOSE OF REVIEW: Dual antiplatelet therapy (DAPT)-aspirin in conjunction with a P2Y12 inhibitor-is the cornerstone of managing patients with acute coronary syndromes post-revascularization, but the clinical response is highly variable, with potentially devastating consequences. Herein, we review the mechanisms underpinning said variability and explore emerging approaches to normalizing therapeutic benefit. RECENT FINDINGS: The potent P2Y12 inhibitors, prasugrel and ticagrelor, exhibit minimal inter-individual variability, replacing clopidogrel in DAPT and achieving greater rates of therapeutic response. However, these benefits decline in later phases when bleeding risk begins to supersede that of ischemia. Guided de-escalation of P2Y12 inhibition as well as shortening DAPT duration have emerged as strategies that retain antithrombotic efficacy while reducing bleeding risk. Aspirin is the other component of DAPT but is also used in isolation for secondary prevention of thrombotic disease. In contrast to the P2Y12 inhibitors, genetic influences on aspirin non-response appear to be outweighed by a triad of clinical factors: non-adherence, enteric aspirin use, and inappropriate dosing according to bodyweight and BMI. Multiple de-escalation strategies for DAPT have been shown to mitigate bleeding risk, but it remains unclear which approach is ideal, necessitating head-to-head investigations to determine which exhibits the most favorable cost-to-benefit ratio. However, there is likely a role for more than one approach in clinical practice, depending on patient risk profile. Our approach to aspirin use is also in need of reassessment: strategies to improve adherence, avoidance of enteric aspirin in cardiac patients, and dose adjustment according to bodyweight and/or BMI are all likely to improve rates of therapeutic response. Moreover, platelet function testing may have a role in identifying patients expected to benefit from primary prophylactic aspirin.

The effect of adverse employment circumstances on physical pain: Evidence from Australian panel data.

Physical pain is a common health problem with great public health implications. Yet evidence on whether adverse employment circumstances shape physical pain is limited. Using longitudinal data from 20 waves (2001-2020) from the Household, Income and Labour Dynamics of Australia Survey (HILDA; N = 23,748), a lagged design, Ordinary Least Squares (OLS) regressions as well as multilevel mixed effect linear regressions, we investigated the association between past accumulated unemployment and recent employment circumstances with physical pain. We found that adults who spent more years unemployed and looking for work subsequently reported greater physical pain (b = 0.034, 95% CI = 0.023, 0.044) and pain interference (b = 0.031, 95% CI = 0.022, 0.038) than those who spent fewer years unemployed. We also found that those experiencing overemployment (working full-time while wanting to work fewer hours) and underemployment (working part-time while wanting to work more hours) reported greater subsequent physical pain (overemployment: b = 0.024, 95% CI = 0.009, 0.039; underemployment: b = 0.036, 95% CI = 0.014, 0.057) and pain interference (overemployment: b = 0.017, 95% CI = 0.005, 0.028; underemployment: b = 0.026, 95% CI = 0.009, 0.043) than those content with their working hours. These results held after controlling for socio-demographic characteristics, occupation, and other health-related factors. These findings are consistent with recent work that suggested that psychological distress can influence physical pain. Understanding how adverse employment circumstances impact physical pain is crucial to the design of health promotion policies.

The scientific revolution that unraveled the astonishing DNA repair capacity of the Deinococcaceae: 40 years on.

The family Deinococcaceae exhibits exceptional radiation resistance and possesses all the necessary traits for surviving in radiation-exposed environments. Their survival strategy involves the coupling of metabolic and DNA repair functions, resulting in an extraordinarily efficient homologous repair of DNA double-strand breaks (DSBs) caused by radiation or desiccation. The keys to their survival lie in the hyperaccumulation of manganous (Mn2+)-metabolite antioxidants that protect their DNA repair proteins under extreme oxidative stress and the persistent structural linkage by Holliday junctions of their multiple genome copies per cell that facilitates DSB repair. This coupling of metabolic and DNA repair functions has made polyploid Deinococcus bacteria a useful tool in environmental biotechnology, radiobiology, aging, and planetary protection. The review highlights the groundbreaking contributions of the late Robert G.E. Murray to the field of Deinococcus research and the emergent paradigm-shifting discoveries that revolutionized our understanding of radiation survivability and oxidative stress defense, demonstrating that the proteome, rather than the genome, is the primary target responsible for survivability. These discoveries have led to the commercial development of irradiated vaccines using Deinococcus Mn-peptide antioxidants and have significant implications for various fields.

Psychological pathways explaining the prospective association between obesity and physiological dysregulation.

OBJECTIVE: Obesity is associated with a range of negative psychological conditions that may also affect physiological health. Across two studies, we tested whether a range of psychological measures explain why obesity is prospectively associated with physiological dysregulation, measured via clinical indicators of cardiovascular, immune system, and metabolic function. METHOD: We used comparable 4-year follow-up representative longitudinal data of U.K. and U.S. older adults (≥50 years) from the English Longitudinal Study of Ageing (2008/2009-2012/2013; Study 1; n = 6,250) and the Health and Retirement Study (2008/2010-2012/2014; Study 2; n = 9,664). A diverse range of psychological measures (e.g., depressive symptoms, life satisfaction, weight stigma, positive affect) were tested as candidate mediators in Studies 1 (n = 14) and 2 (n = 21). RESULTS: Obesity predicted physiological dysregulation at follow-up across both studies. In Study 1, only weight stigma (measured between baseline and follow-up) explained 37% of the association between obesity and physiological dysregulation. In Study 2, only changes in weight stigma from baseline to follow-up (not baseline weight stigma) explained 13% of the effect of obesity on future physiological dysregulation. Mediation by weight stigma in both studies was partially attenuated when changes in body mass index from baseline to follow-up were controlled for. No other psychological measures explained the association between obesity and physiological dysregulation in either study. CONCLUSIONS: The prospective association between obesity and physiological dysregulation was largely not explained by psychological factors. However, experiencing weight stigma is associated with increased weight gain and this process may explain obesity-related declines in physiological health. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Skull-Base Surgery-A Narrative Review on Current Approaches and Future Developments in Surgical Navigation.

Surgical navigation technology combines patient imaging studies with intraoperative real-time data to improve surgical precision and patient outcomes. The navigation workflow can also include preoperative planning, which can reliably simulate the intended resection and reconstruction. The advantage of this approach in skull-base surgery is that it guides access into a complex three-dimensional area and orients tumors intraoperatively with regard to critical structures, such as the orbit, carotid artery and brain. This enhances a surgeon's capabilities to preserve normal anatomy while resecting tumors with adequate margins. The aim of this narrative review is to outline the state of the art and the future directions of surgical navigation in the skull base, focusing on the advantages and pitfalls of this technique. We will also present our group experience in this field, within the frame of the current research trends.

Proceduralist criteria for evaluating interface utility of novel imaging modalities in early phase clinical trials: evaluating the need for standardized criteria.

Accelerating innovation in the space of fluorescence imaging for surgical applications has increased interest in safely and expediently advancing these technologies to clinic through Food and Drug Administration-(FDA-) compliant trials. Conventional metrics for early phase trials include drug safety, tolerability, dosing, and pharmacokinetics. Most procedural imaging technologies rely on administration of an exogenous fluorophore and concurrent use of an imaging system; both of which must receive FDA approval to proceed to clinic. Because fluorophores are classified as medical imaging agents, criteria for establishing dose are different, and arguably more complicated, than therapeutic drugs. Since no therapeutic effect is desired, medical imaging agents are ideally administered at the lowest dose that achieves adequate target differentiation. Because procedural imaging modalities are intended to enhance and/or ease proceduralists' identification or assessment of tissues, beneficial effects of these technologies may manifest in the form of qualitative endpoints such as: 1) confidence; 2) decision-making; and 3) satisfaction with the specified procedure. Due to the rapid expansion of medical imaging technologies, we believe that our field requires standardized criteria to evaluate existing and emerging technologies objectively so that both quantitative and qualitative aspects of their use may be measured and useful comparisons to assess their relative value may occur. Here, we present a 15-item consensus-based survey instrument to assess the utility of novel imaging technologies from the proceduralist's standpoint.

Global trends in emotional distress.

In this study, we examined emotional distress using annual representative survey data from 1.53 million individuals surveyed in 113 countries from 2009 to 2021. Participants reported whether they had experienced worry, sadness, stress, or anger during a lot of the previous day. Within-country estimates showed that the prevalence of feelings of emotional distress increased from 25 to 31% between 2009 and 2021, with those with low levels of education and income experiencing the largest increases in distress. On a global level, the pandemic period was characterized by an initial increase in distress in 2020 followed by recovery in 2021.

Prevalence of perceived discrimination and associations with mental health inequalities in the UK during 2019-2020: A cross-sectional study.

Experiencing discrimination is associated with poorer mental health and the demographic patterning of discrimination may explain social inequalities in mental health. The present research examined prevalence of perceived discrimination in the UK and associations with social inequalities in mental health. Data were taken from the UK Household Longitudinal Study (n = 32,003). Population subgroups (sex, age, ethnicity, health, religiousness, income, education, and occupation), perceived personal discrimination (personal experience) and perceived belonging to a discriminated group (identified as belonging to a group discriminated against in this country), and probable mental health problems (GHQ-12 assessed, cut off 4+) were reported on in 2019/2020. Nineteen percent of participants perceived personal discrimination in the last year, 9% perceived belonging to a discriminated group, and 22% had probable mental health problems. There were significant inequalities in both perceived discrimination and mental health. Being a younger adult, of mixed ethnicity, having health problems, having a university degree, and being unemployed increased risk of mental health problems and these associations were partially explained by perceived discrimination being more common among these groups. Perceived discrimination is common among UK adults, but prevalence differs by population subgroup. Perceived discrimination may contribute to social inequalities in mental health.

Socioeconomic status and depressive symptoms and suicidality: The role of subjective social status.

BACKGROUND: Low socioeconomic status (SES) confers access to material resources and social standing and is an established risk factor of both depressive symptoms and suicidality. Subjective social status (SSS) assesses how people perceive their position within the social hierarchy and has been proposed to impact mental health. This study examined the relationship between SES and depressive symptoms and suicidality and tested whether SSS mediated these associations. METHODS: This study drew on publicly available survey data from the US National Longitudinal Study of Adolescent to Adult Health (Add Health). Participants were surveyed at baseline in 2008 (N = 4948; aged 28.8 years) and at followed up in 2016-2018 (N = 3509; aged 37.8 years). SES was gauged using personal and household income, assets, education, and job prestige. SSS was assessed using the MacArthur Scale. Depressive symptoms were assessed using four-items from the Centre for Epidemiological Studies Scale of Depression (CESD) and participants reported suicidal ideation and suicide attempts in the past year. RESULTS: Both low SES and SSS were associated with elevated levels of depressive symptoms, suicidal ideation, and suicide attempts in cross-sectional and prospective analyses. SSS explained 27 % of the association between SES and depressive symptoms, 51 % of the relationship between SES and suicidal ideation, and 37 % of the link between SES and suicide attempts on average. CONCLUSIONS: These findings contribute to understanding the long-term effects of SSS and suggest that perceptions of status may be a key mechanism through which low SES forecasts the development of depressive symptoms and suicidality.

Acute and longer-term psychological distress associated with testing positive for COVID-19: longitudinal evidence from a population-based study of US adults.

BACKGROUND: The novel coronavirus (SARS-CoV-2) has produced a considerable public health burden but the impact that contracting the disease has on mental health is unclear. In this observational population-based cohort study, we examined longitudinal changes in psychological distress associated with testing positive for coronavirus disease 2019 (COVID-19). METHODS: Participants (N = 8002; observations = 139 035) were drawn from 23 waves of the Understanding America Study, a nationally representative probability-based online panel of American adults followed-up every 2 weeks from 1 April 2020 to 15 February 2021. Psychological distress was assessed using the standardized total score on the Patient Health Questionnaire-4. RESULTS: Over the course of the study, 576 participants reported testing positive for COVID-19. Using regression analysis including individual and time-fixed effects we found that psychological distress increased by 0.29 standard deviations (p < 0.001) during the 2-week period when participants first tested positive for COVID-19. Distress levels remained significantly elevated (d = 0.16, p < 0.01) for a further 2 weeks, before returning to baseline levels. Coronavirus symptom severity explained changes in distress attributable to COVID-19, whereby distress was more pronounced among those whose symptoms were more severe and were slower to subside. CONCLUSIONS: This study indicates that testing positive for COVID-19 is associated with an initial increase in psychological distress that diminishes quickly as symptoms subside. Although COVID-19 may not produce lasting psychological distress among the majority of the general population it remains possible that a minority may suffer longer-term mental health consequences.