Obesity, psychological well-being related measures, and risk of seven non-communicable diseases: evidence from longitudinal studies of UK and US older adults.

BACKGROUND: We examined the role of psychological well-being related measures in explaining the associations between obesity and increased risk of non-communicable diseases (NCDs: hypertension, heart disease, stroke, diabetes, arthritis, cancer, and memory-related disease) in older adults. METHODS: Data were from the English Longitudinal Study of Ageing (ELSA), UK (baseline: Wave 4-2008/2009; n = 8127) and the Health and Retirement Study (HRS), US (baseline: Waves 9 and 10-2008/2010; n = 12,477). Objective body mass index was used to define obesity. A range of psychological well-being related measures (e.g., depressive symptoms, life satisfaction) was available in ELSA (n = 7) and HRS (n = 15), and an index of overall psychological well-being was developed separately in each study. NCDs were from a self-reported doctor diagnosis and/or other assessments (e.g., biomarker data) in both studies; and in ELSA, NCDs from linked hospital admissions data were examined. Longitudinal associations between obesity status, psychological well-being measures, and NCDs were examined using Cox proportional hazard models (individual NCDs) and Poisson regression (a cumulative number of NCDs). Mediation by psychological well-being related measures was assessed using causal mediation analysis. RESULTS: Obesity was consistently associated with an increased prospective risk of hypertension, heart disease, diabetes, arthritis, and a cumulative number of NCDs in both ELSA and HRS. Worse overall psychological well-being (index measure) and some individual psychological well-being related measures were associated with an increased prospective risk of heart disease, stroke, arthritis, memory-related disease, and a cumulative number of NCDs across studies. Findings from mediation analyses showed that neither the index of overall psychological well-being nor any individual psychological well-being related measures explained (mediated) why obesity increased the risk of developing NCDs in both studies. CONCLUSION: Obesity and psychological well-being may independently and additively increase the risk of developing NCDs.

Does Freehand, Patient-specific Instrumentation or Surgical Navigation Perform Better for Allograft Reconstruction After Tumor Resection? A Preclinical Synthetic Bone Study.

BACKGROUND: Joint-sparing resection of periarticular bone tumors can be challenging because of complex geometry. Successful reconstruction of periarticular bone defects after tumor resection is often performed with structural allografts to allow for joint preservation. However, achieving a size-matched allograft to fill the defect can be challenging because allograft sizes vary, they do not always match a patient's anatomy, and cutting the allograft to perfectly fit the defect is demanding. QUESTIONS/PURPOSES: (1) Is there a difference in mental workload among the freehand, patient-specific instrumentation, and surgical navigation approaches? (2) Is there a difference in conformance (quantitative measure of deviation from the ideal bone graft), elapsed time during reconstruction, and qualitative assessment of goodness-of-fit of the allograft reconstruction among the approaches? METHODS: Seven surgeons used three modalities in the same order (freehand, patient-specific instrumentation, and surgical navigation) to fashion synthetic bone to reconstruct a standardized bone defect. National Aeronautics and Space Administration (NASA) mental task load index questionnaires and procedure time were captured. Cone-beam CT images of the shaped allografts were used to measure conformance (quantitative measure of deviation from the ideal bone graft) to a computer-generated ideal bone graft model. Six additional (senior) surgeons blinded to modality scored the quality of fit of the allografts into the standardized tumor defect using a 10-point Likert scale. We measured conformance using the root-mean-square metric in mm and used ANOVA for multipaired comparisons (p < 0.05 was significant). RESULTS: There was no difference in mental NASA total task load scores among the freehand, patient-specific instrumentation, and surgical navigation techniques. We found no difference in conformance root-mean-square values (mean ± SD) between surgical navigation (2 ± 0 mm; mean values have been rounded to whole numbers) and patient-specific instrumentation (2 ± 1 mm), but both showed a small improvement compared with the freehand approach (3 ± 1 mm). For freehand versus surgical navigation, the mean difference was 1 mm (95% confidence interval [CI] 0.5 to 1.1; p = 0.01). For freehand versus patient-specific instrumentation, the mean difference was 1 mm (95% CI -0.1 to 0.9; p = 0.02). For patient-specific instrumentation versus surgical navigation, the mean difference was 0 mm (95% CI -0.5 to 0.2; p = 0.82). In evaluating the goodness of fit of the shaped grafts, we found no clinically important difference between surgical navigation (median [IQR] 7 [6 to 8]) and patient-specific instrumentation (median 6 [5 to 7.8]), although both techniques had higher scores than the freehand technique did (median 3 [2 to 4]). For freehand versus surgical navigation, the difference of medians was 4 (p < 0.001). For freehand versus patient-specific instrumentation, the difference of medians was 3 (p < 0.001). For patient-specific instrumentation versus surgical navigation, the difference of medians was 1 (p = 0.03). The mean ± procedural times for freehand was 16 ± 10 minutes, patient-specific instrumentation was 14 ± 9 minutes, and surgical navigation techniques was 24 ± 8 minutes. We found no differences in procedures times across three shaping modalities (freehand versus patient-specific instrumentation: mean difference 2 minutes [95% CI 0 to 7]; p = 0.92; freehand versus surgical navigation: mean difference 8 minutes [95% CI 0 to 20]; p = 0.23; patient-specific instrumentation versus surgical navigation: mean difference 10 minutes [95% CI 1 to 19]; p = 0.12). CONCLUSION: Based on surgical simulation to reconstruct a standardized periarticular bone defect after tumor resection, we found a possible small advantage to surgical navigation over patient-specific instrumentation based on qualitative fit, but both techniques provided slightly better conformance of the shaped graft for fit into the standardized post-tumor resection bone defect than the freehand technique did. To determine whether these differences are clinically meaningful requires further study. The surgical navigation system presented here is a product of laboratory research development, and although not ready to be widely deployed for clinical practice, it is currently being used in a research operating room setting for patient care. This new technology is associated with a learning curve, capital costs, and potential risk. The reported preliminary results are based on a preclinical synthetic bone tumor study, which is not as realistic as actual surgical scenarios. CLINICAL RELEVANCE: Surgical navigation systems are an emerging technology in orthopaedic and reconstruction surgery, and understanding their capabilities and limitations is paramount for clinical practice. Given our preliminary findings in a small cohort study with one scenario of standardized synthetic periarticular bone tumor defects, future investigations should include different surgical scenarios using allograft and cadaveric specimens in a more realistic surgical setting.

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.

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.

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.

The psychological burden associated with metabolic syndrome: Evidence from UK and US older adults.

Introduction: We examined the psychological burden associated with metabolic syndrome (MetSyn). Methods: We used comparable longitudinal data of older adults (≥50 years) from the UK (English Longitudinal Study of Aging) and the US (Health and Retirement Study). We defined MetSyn based on biomarker assessments (e.g., blood pressure, impaired glycemic control). Using regression models, we tested a range of individual psychological outcomes (e.g., depressive symptoms) associated with MetSyn. We also examined whether these psychological outcomes may explain or moderate the link between MetSyn and non-communicable diseases (NCDs). Findings: MetSyn was associated cross-sectionally with a range of psychological outcomes, including depression, anxiety, loneliness, hopelessness, cynical hostility, social strain, negative affect and decreased positive affect, social support and purpose in life. There was no convincing evidence that psychological factors interacted with or explained (mediated) the relationship between MetSyn and increased risk of developing NCD over 10-year follow-ups. Conclusions: MetSyn and the psychological burden outcomes examined may have independent effects on NCD risk.

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.

Changes in the prevalence of perceived discrimination and associations with probable mental health problems in the UK from 2015 to 2020: A repeated cross-sectional analysis of the UK Household Longitudinal Study.

Background: Significant social and political changes occurred in the UK between 2015 and 2020. Few studies have examined population level trends in experiencing discrimination and mental health problems during this period. Aims: To determine prevalence trends in perceived discrimination and probable mental health problems amongst UK adults during 2015-2020. Method: Repeated cross-sectional data from the UK Household Longitudinal Study was used to estimate nationally representative trends in perceived discrimination and probable mental health problems (GHQ-12; 4+ threshold) among adults between 2015/2016-2019/2020 (25,756 observations). Weighted logistic regression models with post-estimation margins commands determined changes between survey waves controlling for sociodemographic characteristics. Mediation models explored whether changes in perceived discrimination prevalence trends explained trends in probable mental health problems. Results: From 2015/2016 to 2019/2020 perceived discrimination and probable mental health problems increased significantly by 6·1% (95% CI: 3·4-8·8, p <·001) and 4·5% (95% CI: 1·3-7·7, p = ·006), respectively. These changes did not tend to reliably differ by sociodemographic grouping. Increased prevalence of probable mental health problems from 2015/2016 to 2019/2020 was partially explained (15·2% of association mediated) by the increase in perceived discrimination observed during the same time period. Conclusions: Amongst UK adults, the prevalence of perceived discrimination and probable mental health problems increased between 2015/2016 to 2019/2020. Increases in perceived discrimination partially explained increases in probable mental health problems. National measures designed to reduce both discrimination and mental health problems have potential to make substantial improvements to public health and should be prioritised in the UK.

Evaluation of a 3D Printed Silicone Oral Cavity Cancer Model for Surgical Simulations.

Adequate surgical margins are essential in oral cancer treatment, this is, however, difficult to appreciate during training. With advances in training aids, we propose a silicone-based surgical simulator to improve training proficiency for the ablation of oral cavity cancers. A silicone-based tongue cancer model constructed via a 3D mold was compared to a porcine tongue model used as a training model. Participants of varying surgical experience were then asked to resect the tumors with clear margins, and thereafter asked to fill out a questionnaire to evaluate the face and content validity of the models as a training tool. Eleven participants from the Otolaryngology-Head and Neck Surgery unit were included in this pilot study. In comparison to the porcine model, the silicone model attained a higher face (4 vs. 3.6) and content validity (4.4 vs. 4.1). Tumor consistency was far superior in the silicone model compared to the porcine model (4.1 vs. 2.8, p = 0.0042). Fellows and staff demonstrated a better margin clearance compared to residents (median 3.5 mm vs. 1.0 mm), and unlike the resident group, there was no incidence of positive margins. The surgical simulation was overall useful for trainees to appreciate the nature of margin clearance in oral cavity cancer ablation.

Understanding the impact of slowing disease progression for individuals with biomarker confirmed early symptomatic Alzheimer's disease.

Recent advances in development of amyloid-targeting therapies support the potential to slow the rate of progression of Alzheimer's disease. We conducted a narrative review of published evidence identified through a targeted search of the MEDLINE and EMBASE databases (2020-2023), recent presentations at disease-specific conferences, and data updates from cohort studies in Alzheimer's disease to describe the trajectory of progression of Alzheimer's disease. Our findings enable interpretation of clinical trial results and the value associated with slowing disease progression across outcomes of relevance to patients, care partners, clinicians, researchers and policymakers.Even at the earliest stages, Alzheimer's disease imposes a substantial burden on individuals, care partners, and healthcare systems. The magnitude of burden increases with the rate of disease progression and symptom severity, as worsening cognitive decline and physical impairment result in loss of functional independence. Data from cohort studies also indicate that slowing disease progression is associated with decreased likelihood of needing extensive clinical care over at least 5 years, decreased care partner burden, and substantial individual and societal cost savings.Slowed disease progression is of significant benefit to individuals with Alzheimer's disease, their loved ones, and the healthcare system. As clinicians and policymakers devise strategies to improve access to treatment earlier in the disease spectrum, they should carefully weigh the benefits of slowing progression early in the disease (e.g., preservation of cognitive and functional abilities, as well as relative independence) to individuals, their loved ones, and broader society.

Time to ECG diagnosis delays inter-hospital transfer to revascularization in STEMI patients presenting to a regional emergency department: a five-year audit.

BACKGROUND: Reducing the door-to-balloon time (D2BT) in ST-elevation myocardial infarction (STEMI) patients maximizes myocardial salvage and mitigates morbidity/mortality. AIMS: To assess the D2BT in STEMI patients requiring inter-hospital transfer for revascularization and identify any potential causes of delay. METHODS: Consecutive patients presenting to the Connolly Hospital Blanchardstown (CHB) emergency department (ED) who were transferred to the Mater Misericordiae University Hospital in Dublin for primary percutaneous coronary intervention from January 2018 to October 2022 were identified in a regional database and their D2BTs calculated. D2BTs were further sub-categorized into key intervals to identify any potential causes of delay. RESULTS: A total of 90 patients were included for analysis, with a median D2BT of 117.5 min (interquartile range [IQR]: 99.3-170.8 min) and 52.5% of patients achieving the ≤ 120 min target. Despite being the shortest interval considered, the time from arrival at the CHB ED to diagnostic electrocardiogram (ECG) was a substantial contributor to the overall delay to revascularization given its wide variability (median: 18.0 min; IQR: 9.0-46.8 min), with only 28.8% of patients achieving the ≤ 10 min target. CONCLUSIONS: Nearly half of the patients studied failed to achieve the overall target D2BT for revascularization. The time from arrival at the CHB ED to diagnostic ECG was identified as a substantial contributor to this failure, with a median time almost twice that of the target and a quarter of all patients spending longer than 46.8 min. These findings highlight a need to improve the implementation of ECG triage and interpretation in the ED.

Hydrogel-chitosan and polylactic acid-polycaprolactone bioengineered scaffolds for reconstruction of mandibular defects: a preclinical in vivo study with assessment of translationally relevant aspects.

Background: Reconstruction of mandibular bone defects is a surgical challenge, and microvascular reconstruction is the current gold standard. The field of tissue bioengineering has been providing an increasing number of alternative strategies for bone reconstruction. Methods: In this preclinical study, the performance of two bioengineered scaffolds, a hydrogel made of polyethylene glycol-chitosan (HyCh) and a hybrid core-shell combination of poly (L-lactic acid)/poly ( ε -caprolactone) and HyCh (PLA-PCL-HyCh), seeded with different concentrations of human mesenchymal stromal cells (hMSCs), has been explored in non-critical size mandibular defects in a rabbit model. The bone regenerative properties of the bioengineered scaffolds were analyzed by in vivo radiological examinations and ex vivo radiological, histomorphological, and immunohistochemical analyses. Results: The relative density increase (RDI) was significantly more pronounced in defects where a scaffold was placed, particularly if seeded with hMSCs. The immunohistochemical profile showed significantly higher expression of both VEGF-A and osteopontin in defects reconstructed with scaffolds. Native microarchitectural characteristics were not demonstrated in any experimental group. Conclusion: Herein, we demonstrate that bone regeneration can be boosted by scaffold- and seeded scaffold-reconstruction, achieving, respectively, 50% and 70% restoration of presurgical bone density in 120 days, compared to 40% restoration seen in spontaneous regeneration. Although optimization of the regenerative performance is needed, these results will help to establish a baseline reference for future experiments.