Matched Controls Research Articles

Association of park renovation with park use in New York City

Abstract Background Equity-driven citywide park redesign and renovation, such as the Community Parks Initiative (CPI), has the potential to increase park use and opportunities for physical activity in underserved communities. The objective of this study was to evaluate changes in patterns of park use following park redesign and renovation in low-income New York City (NYC) neighborhoods. Methods The Physical Activity and Redesigned Community Spaces study was a prospective quality improvement pre-post intervention study design with 33 intervention and 21 matched control neighborhood parks. Data were collected at baseline (prerenovation) and 2 follow-up points (3 months and 1-year post renovation) between 2016 to 2022 summers. Main outcomes encompassed park use and physical activity levels assessed using the well-validated System for Observing Play and Recreation in Communities. Park use was quantified by total number of park users, categorized by age group (≤20 years vs ≥ 21 years), sex, and physical activity level (sitting or standing vs walking or vigorous activity). Changes in outcomes between groups were compared via the generalized estimation equation. Results A total of 28,322 park users were observed across 1,458 scans. At baseline, 59.7% were 20 years or younger, 46.3% were female, and 43.8% were sitting or standing. Intervention parks showed more net park users compared with control parks from baseline to the final follow-up (difference-in-difference relative rate ratio, 1.69 [95% CI, 1.22-2.35] users/scan). The association was driven by a significant increase in adult users at intervention parks and an overall decrease in all users at control parks. Conclusions In this quality improvement study, park redesign and renovation were positively associated with park use in low-income neighborhoods. However, park renovations may need to be accompanied by other programmatic strategies to increase physical activity.

Association of polymorphism of apolipoprotein e gene with acute myocardial infarction and its short term clinical outcome

Abstract Background/Introduction Myocardial infarction (MI) is a multifactorial disease influenced by environmental and genetic factors. Apolipoprotein E (ApoE) is a protein incorporated into serum lipoproteins directing their catabolism via binding to receptors. It is a structural component of both chylomicrons and very low density lipoprotein (VLDL) remnants. ApoE is thought to play a central role in atherosclerosis by participating in overall plasma cholesterol homeostasis. In addition to other classical risk factors, positive family history of cardiovascular disease (CVD) has been found to be significantly and independently associated with MI in epidemiological studies (1). Besides traditional cardiovascular risk factors it is likely that additional genetic factors like ApoE gene polymorphism may interact with environmental factors to determine overall cardiovascular risk of an individual to develop MI. Purpose The purpose of our study was to determine the risk of association of variants of ApoE gene with Acute Myocardial Infarction. Moreover, we also wanted to study the impact of ApoE gene polymorphism in short term major adverse cardiac events (MACE) in patients with MI not willing for coronary intervention. Methods In this case control study a total of 200 consecutively admitted AMI patients admitted to the coronary care unit of our hospital were enrolled to the study along with 200 age and gender matched controls admitted during the same time period . ApoE gene polymorphism was detected by DNA extraction, DNA amplification by PCR in a DNA thermal cycler followed by restriction enzyme digestion(2). Chi square test was used to investigate the difference in genotype and allele frequencies in casend controls and also between observed and expected frequencies in the realm of Hardy-Weinberg equilibrium. Odds Ratio (OR) with 95 % confidence interval and p values were calculated while analysing the association of different genotypes of ApoE genetic polymorphism with the disease and MACE. Logistic regression analysis was carried out amongst the groups under consideration to find the unadjusted OR and adjusted OR of the genotypes in relation to the disease.p<0.05 was considered as significant Analysis was done in SPSS software. Results Besides the traditional risk factors Apo E4 allele (OR 2.298, CI 1.305-4.044 ) and Apo E3/E4 genotype (OR 2.116, CI 1.008-4.443, p=0.048) showed strong of association with the disease. There was a higher population of Apo E3/E4 genotypes and Apo E2/E3 genotypes with MACE events (25.6% and 28.6%), while the common ApoE3/E3 genotypes had a MACE event of 10.5 %. However, the difference was not significant (p=0.071, Χ 2 =8.63 df =4). Similarly, ApoE4 allele showed a non significantly higher MACE events (p=0.22, Χ 2 =3.01 df =4) Conclusion ApoE4 allele and ApoE3/E4 genotype are strongly and independently associated with AMI.RISK FACTORS AND RISK OF MIGenotype and MACE

Clinical and biochemical assessments of circulating High Mobility Group Box Protein1 in children with epilepsy: relation to cognitive function and drug responsiveness.

Childhood epilepsy is a major health concern posing a significant burden and having disastrous consequences for cognitive function. High Mobility Group Box1 (HMGB1) is an activator of neuroinflammation, and it is possibly involved in the initiation and progression of epilepsy. We aimed to investigate circulating HMGB1 in children with epilepsy and its connection to cognitive function and drug responsiveness. Case-control research included 100 epileptic youngsters and 100 healthy matched controls. Serum HMGB1 was measured using a commercially available ELISA assay. Cognitive functions were evaluated by the Stanford-Binet test 5th edition. Drug-resistant epilepsy (DRE) was found in 37% of the investigated patients. Epileptic children have lower cognitive function parameter levels versus the control group and lower cognitive function in the DRE group compared to the drug-responsive group (P-value < 0.0001). HMGB1 levels were significantly higher in the patients' group (6.279µg/L) compared to the control group (2.093µg/L) and in the drug-resistant group (14.26µg/L) versus the drug-responsive group (4.88µg/L). A significant negative correlation was detected between HMGB1 with Full-scale IQ (r = - 0.547, P = 0.000), Visual-spatial reasoning (r = - 0.501, P = 0.000), fluid reasoning (r = - 0.510, P = 0.000), and working memory (r = - 0.555, P = 0.000). Serum HMGB1 cut-off levels > 6.85µg/L differentiate drug-responsive from resistant patients. Elevated HMGB1 levels, especially in patients with drug-resistant epilepsy, correlate negatively with cognitive performance, emphasizing its importance as a potential marker for early prediction of drug resistance and impairment of cognitive function.

Impact of atrial fibrillation on cardiac autonomic function in elderly patients

Abstract Introduction Cardiac autonomic dysfunction has been linked to an increased risk of mortality (1), stroke and silent brain lesions (2) and cognitive impairment (3) in patients with atrial fibrillation (AF). However, the impact of AF on cardiac autonomic function is poorly understood. Purpose We aimed to explore the impact of AF on cardiac autonomic function by comparing AF patients with a matched control cohort without AF. Methods We enrolled patients with and without AF from two ongoing, prospective, multicenter cohort studies (Swiss-AF Cohort and Swiss-AF Control) if they had a high-resolution 16-lead resting ECG recording in sinus rhythm for a duration of 5 minutes at baseline visit. Cardiac autonomic function was quantified by periodic repolarization dynamics (PRD), a marker of repolarization instability associated with sympathetic activity. PRD was quantified by means of wavelet analysis, as validated previously (4). Cardiac autonomic dysfunction was defined present if PRD exceeded the established cut-off of 10.0 deg2 (5). We built multivariable adjusted linear and logistic regression models to explore the association of AF with PRD and cardiac autonomic dysfunction. Results We included 2077 patients, 1113 (54%) from the AF cohort and 964 (46%) from the matched non-AF cohort. Baseline characteristics were well balanced between the groups (mean age 71 vs. 73 years in patients with and without AF, mean CHA2DS2-VASc score 3.0 vs. 3.5, female sex 31.3% vs. 36.6%). The median PRD was 18.2 deg2 (IQR 9.9-25.4) in patients with AF and 15.8 deg2 (IQR 8.1 -23.0) in patients without AF (p&amp;lt;0.001, Figure). 832 (75%) of the AF patients suffered from cardiac autonomic dysfunction, vs. 656 (68%) of the non-AF patients (p&amp;lt;0.001). Multivariable adjusted linear regression analysis revealed an independent association of AF with continuous levels of PRD (beta-coefficient -1.57, 95% CI -2.64 - -0.488, p=0.004). Further, AF was independently associated with the presence of cardiac autonomic dysfunction (Odds Ratio 1.48, 95% CI 1.18-1.87, p&amp;lt;0.001, Table). Conclusion In this cross-sectional analysis of a patient population with and without AF, AF was independently associated with increased PRD values, reflecting sympathetic predominance, and with the presence of cardiac autonomic dysfunction. These findings implicate a relevant role of AF in the development of cardiac autonomic dysfunction in elderly patients.Figure

Monocytic mitochondrial dysfunction and impaired monocytic bioenergetic profile in patients with heart failure symptoms in post-COVID syndrome

Abstract Introduction/Purpose Approximately 35% of COVD-19 patients have persistent symptoms similar to congestive heart failure. The so called post-Covid syndrome, which includes symptoms such as dyspnea and angina pectoris, is presumably associated to cellular metabolism and oxidative stress, yet whether mitochondrial function is impaired in post-COVID patients is still unclear. We thus investigated the mitochondrial function in monocytes of symptomatic post-COVID patients compared to matched controls. Methods Patients with persisting cardiac symptoms in their daily activities and diagnosed with post-COVID syndrome (n=14) were recruited and matched with unaffected controls (n=10) for age, sex and cardiovascular risk factors. Structural heart disease was excluded through cardiac work-up (echocardiography, functional stress testing and when necessary coronary angiography). Primary monocytes were isolated using negative selection method. The bioenergetic status of the monocytes was assessed using the Agilent Seahorse XF Cell Mito Stress Test without and after modulation of reactive oxygen species (ROS) by buthionine sulfoximine (BSO). Results CD14++ monocytes isolated from post-COVID patients showed non-significantly increased basal proton leak (p=0.57), reduced maximal respiration, and reserved respiratory capacity (p=0.19) compared to controls. Induction of additional oxidative stress by ROS modulation revealed a significantly impaired bioenergetic profile of monocytes in terms of reduction of basal respiration (3-fold, p=0.0005), maximal respiration (4-fold, p=0.004) and spare respiratory capacity (5-fold, p=0.008). Conclusions We demonstrated an impaired bioenergetic profile of CD14++ monocytic mitochondria in patients suffering from heart failure symptoms following COVID-19 infection. Whether the findings provide a novel biomarker for measuring systemic oxidative stress conditions or whether there is a direct link between symptoms of post-COVID disease and monocytic function needs to be addressed in further studies.

Cardiac structure and function in people with cystic fibrosis

Abstract Background Cystic fibrosis (CF) is an autosomal recessive disease affecting multiple organs, however the extent of cardiac involvement in CF is yet to be determined. The remarkable therapeutic advancements with new highly effective CF transmembrane conductance regulator (CFTR) modulator treatment and subsequent increase in life expectancy substantiates further research. Purpose We aimed to explore the prevalence of abnormalities and potential subclinical alterations in cardiac structure and function in adults with CF compared to matched controls and investigate potential cardiovascular risk factors in people with CF (pwCF). Methods In this cross-sectional study, 104 adult pwCF in Denmark underwent clinical and echocardiographic examination. All participants were matched 1:1 with controls from the general population on age and sex. Uni- and multivariable linear regression models with adjustment for heart rate, FEV1, smoking status, hypertension and CF-related diabetes (CFRD) were used to test for differences in echocardiographic parameters between cases and controls. Abnormal cardiac function was defined as left ventricular ejection fraction (LVEF) &amp;lt;50%, left ventricular (LV) global longitudinal strain (GLS) &amp;lt; 16% or presence of diastolic dysfunction. Uni- and multivariable logistic regression models adjusted for age, sex, homozygous genotype, FEV1/FVC, BMI, smoking status, CFRD, pancreatic insufficiency, hypertension, and ischemic heart disease were performed to assess associations between potential risk factors and cardiac dysfunction in CF. Forest plots were constructed to visually represent the findings. Results Of 104 pwCF, 44% were female, mean age was 34 years, 93% received CFTR modulator treatment, and 91% had mutations with only minimal CFTR function (mutation class I-III). The prevalence of abnormal cardiac function in pwCF was 44% versus 22% in controls. Compared to controls, pwCF were found to have smaller LV dimensions, worse LV diastolic function, and more impaired right ventricle (RV) as well as LV systolic function (Table). After multivariable adjustment, LV diastolic function as well as LV and RV systolic function remained impaired in pwCF as compared to controls. Male sex and decreasing FEV1/FVC ratio remained independently associated with abnormal cardiac function in pwCF (male sex: OR 3.94 (1.56; 9.95), p=0.004 and FEV1/FVC ratio: OR 2.05 per 0.1 unit decrease (1.21; 3.52), p=0.008, respectively) (Figure). Conclusion Both left- and right-sided cardiac alterations were found in pwCF. After adjustments for potential risk factors, both RV and LV systolic measures remained altered in pwCF, compared to controls. Male sex and decreasing pulmonary function evaluated by FEV1/FVC-ratio were identified as factors associated with abnormal cardiac function in pwCF.Figure

Influence of prior heart valve intervention on treatment and disease trajectory after diagnosis of heart failure with reduced ejection fraction

Abstract Background and aim Among patients with heart failure with reduced ejection fraction (HFrEF), knowledge is scarce on whether patients with prior valvular heart disease (VHD) intervention are distinct regarding clinical characteristics, treatment, and prognosis. Methods Using the Danish Heart Failure Registry and nationwide administrative registries, we identified patients with new-onset HFrEF from 2008 to 2021. Within this cohort, patients with a prior VHD intervention were identified and matched 1:5 on age-, sex-, in/outpatient presentation, and year of HFrEF diagnosis with remaining patients (controls). Outcomes were 1) baseline use and up-titration of guidelines-directed medical therapy (GDMT) and implementation of implantable cardioverter-defibrillator or cardiac resynchronization therapy with pacemaker/defibrillator (ICD/CRT-P/D) at 6 months follow-up, and 2) a composite of HF hospitalization or all-cause death at 3 years follow-up. The Kaplan-Meier estimator and Cox regression models, adjusted for HF severity, socioeconomic status, and major comorbidities, were used to compare the composite outcome, with patients without prior heart valve intervention as reference. Results The study cohort comprised 32,713 patients, of whom 1196 (3.6%) underwent a prior VHD intervention (median time since intervention 10 months). After matching, the study population were 1151 cases (median age 74 years, 82% men), and 3769 matched controls. Among cases and controls, median left ventricular ejection fraction was similar (30% vs. 30%) and the proportion in New York Heart Association (NYHA) class II was alike (82% vs 83%). At the time of HFrEF diagnosis, numerically more cases were on a beta-blocker (62% vs. 53%), ACEi/ARB/ARNI (48% vs. 44%), MRA (19% vs. 14%), and more had an implementation of (ICD/CRT-P/D) (17 % vs. 7%) (Figure 1). At 6 months, ≥ 50% of the daily target dose was achieved in (46% vs. 46%) for beta-blockers, (47% vs. 47%) for ACEi/ARBs/ARNI, (31% vs. 33%) for MRA, and implementation of ICD/CRT-P/D was attained in (28% vs. 18%), among cases and controls, respectively (Figure 1). The 3-year risk of HF hospitalization or all-cause death was 25% in cases and 24% in controls (Figure 2) with no significant differences (hazard ratio (HR) 0.95 , 95% confidence interval (CI) 0.84-1.08) compared to controls. Conclusions Patients with new-onset HFrEF and prior VHD interventions received more GDMT and had a higher implementation of ICD/CRT-P/D at the time of HFrEF diagnosis. However, following diagnosis, no major differences in GDMT initiation and up-titration, implementation of ICD/CRT-P/D, and the adjusted rates of HF hospitalization or all-cause death were observed among patients with and without prior heart valve intervention.Figure 1 Guideline-directed medicationFigure 2 Crude cumulative risk

Evolution of mate harm resistance in females from Drosophila melanogaster populations selected for faster development and early reproduction.

Interlocus sexual conflict is predicted to result in sexually antagonistic coevolution between male competitive traits, which are also female-detrimental, and mate harm resistance (MHR) in females. Little is known about the connection between life-history evolution and sexually antagonistic coevolution. Here, we investigated the evolution of MHR in a set of experimentally evolved populations, where mate-harming ability has been shown to have substantially reduced in males as a correlated response to the selection for faster development and early reproduction. We measured mortality and fecundity of females of these populations and those of their matched controls, under different male exposure conditions. We observed that the evolved females were more susceptible to mate harm - suffering from significantly higher mortality under continuous exposure to control males within the twenty-day assay period. Though these evolved females are known to have shorter lifespan, substantially higher mortality was not observed under virgin and single-mating conditions. We used fecundity data to show that this higher mortality in the experimentally evolved females was not due to the cost of egg production, and hence can only be attributed to reduced MHR. Further analysis indicated that this decreased MHR is unlikely to be due purely to the smaller size of these females. Instead, it is more likely to be an indirect experimentally evolved response attributable to the changed breeding ecology, and/or male trait evolution. Our results underline the implications of changes in life history traits, including lifespan, to the evolution of MHR in females.

Successful non-invasive imaging of the coronary artery IMT in pediatric patients with Kawasaki disease using high-resolution echocardiography

Kawasaki Disease (KD) is a multisystemic vasculitis of medium- and small-sized arteries. Abnormal intimal thickening may develop in the involved arterial area after regression of coronary artery aneurysm (CAA). Intimal dysfunction may induce local stenosis or arteriosclerosis in the future. In this case–control study, we investigated 29 consecutive KD patients [20 male, median current age, 7.9 years; median follow-up duration, 5.7 years] and a group of 29 healthy matched controls (CON) [19 male, median current age, 10.8 years]. They were assesed and compared for CAA, LVFS, GCS, GLS, coronary artery (CA) Z scores, carotid intima-media thickness (IMT) and coronary artery IMT by high-resolution transthoracic echocardiography (hrTTE). Coronary artery IMT (caIMT) was significantly higher in patients with a maximal CA Z score > 2.5 in acute KD than in CON: KD caIMT: 0.62 mm [IQR, 0.57–0.72 mm] vs. 0.53 mm [0.51–0.60 mm], p = 0.043. CAAs were found in 15 (51.7%) patients with acute KD. The maximal median LCA Z score in acute KD was 2.57z [IQR, 1.93—3.2z] and in follow-up −0.39z [IQR, −1.25 to −0.36z]. There was no significant difference in carotid IMT between KD patients and CON. Signs of CA intima-media thickening were detected by hrTTE in patients with a maximal CA Z score > 2.5 in acute KD. These data indicate that these patients may be at risk for cardiovascular sequale even in the absence of permanent CA luminal abnormalities. Therefore long-term follow-up of this group of KD patients may be required.

Kidney Transplantation in Patients with Polycystic Kidney Disease: Increased Risk of Infection Does Not Compromise Graft and Patient Survival

Abstract Background Patients with autosomal dominant polycystic kidney disease (ADPKD) represent &amp;gt;10% of patients awaiting kidney transplantation. These patients are prone to potentially severe urinary tract (UTI) and liver cyst infections after transplantation. Whether such infections compromise outcome is unclear. Methods Between 2000 and 2017 we performed 193 kidney transplantations in patients with ADPKD. In 189 patients we assessed the occurrence, frequency and severity of infection episodes requiring inpatient treatment and their impact on graft and patient outcomes compared with 189 matched controls. Risk factors were analyzed by uni- and multivariable analyses. Results During a mean observation period of 77 months UTIs occurred more frequently in ADPKD patients (39.1% vs. 26.7%, p=0.022; 0.8±1.4 vs. 0.5±1.1 episodes, p&amp;lt;0.001). Eight ADPKD patients suffered from 19 episodes of liver cyst infection. Steroid medication (RR 3.04; p&amp;lt;0.001) and recipient age (RR 1.05; p=0.003) increased the risk for UTI/urosepsis, while nephrectomy reduced it (unilateral: RR 0.60; p=0.088; bilateral: RR 0.45; p=0.020). Patient survival was similar in both groups. The risk of graft failure was lower in ADPKD patients (HR 0.67; p=0.047) due to a lower risk of death-censored graft loss (HR 0.47; p=0.014). Donor age (HR 1.34; p=0.002) and rejection (HR 8.47; p&amp;lt;0.001) were risk factors for death-censored graft loss. Conclusions ADPKD patients are at increased risk of UTI and liver cyst infection after transplantation. Steroid medication and recipient age seem to increase the risk of UTI/urosepsis, while nephrectomy seems to reduce it. Nevertheless, patient survival was similar compared to non-ADPKD patients and death-censored graft survival even better.

Altered neural activities during emotion regulation in depression: a meta-analysis.

Deficient neural activities during emotion regulation have been reported in depression. We sought to conduct a meta-analysis to provide a comprehensive description of these neural alterations during use of emotion regulation strategies among patients with depression, including major depressive disorder (MDD) and bipolar disorder (BD). We identified neuroimaging studies of abnormal neural activities during emotion regulation in depression. We extracted the peak coordinates and effect sizes of differences in brain activity between patients and healthy controls. Using seed-based d mapping, we conducted voxel-wise meta-analyses of the neural activation pattern differences between the 2 groups across conditions involving emotion regulation and those where emotion regulation was not needed. We included 33 studies reporting 34 data sets, including 23 involving MDD (571 people with MDD and 578 matched controls) and 11 involving BD (358 people with BD and 369 matched controls). Overall, compared with controls, patients with depression showed hyperactivity in the insula and postcentral gyrus, and hypoactivity in the prefrontal part of the inferior, middle, and superior frontal gyrus, the middle temporal gyrus, and the supplementary motor area. In subgroup analyses, data from patients with MDD and studies focused on decreasing negative emotions or using the emotional strategy of reappraisal reported specific hypoactivity in the middle cerebellar peduncles. Given limited studies involving patients with BD, we were unable to detect the common and distinct abnormalities in neural activation between MDD and BD. We did not conduct any meta-regression analyses because of limited information. In this meta-analysis, we identified hyperactivity in brain regions associated with emotional experience and hypoactivity in brain regions associated with cognitive control during emotion regulation among patients with depression, relative to healthy controls. These findings could help indicate a target for future interventions aimed at increasing emotion regulation capacity for patients with depression.

Transmission line model as a digital twin for abdominal aortic aneurysm patients

We investigated the potential of the transmission line model as a digital twin of aneurysmal aorta by comparatively analyzing how a uniform lossless tube-load model were fitted to the carotid and femoral artery tonometry waveforms pertaining to (i) 79 abdominal aortic aneurysm (AAA) patients vs their matched controls (CON) and (ii) 35 AAA patients before vs after endovascular aneurysm repair (EVAR). The uniform lossless tube-load model fitted the tonometry waveforms pertaining to AAA as well as CON and EVAR. In addition, the parameters in the tube-load model exhibited physiologically explainable changes: when normalized, both pulse transit time and reflection coefficient increased with AAA and decreased after EVAR, which can be explained by the increase in arterial compliance and the decrease in arterial inertance due to the aortic expansion associated with AAA. In sum, the tube-load model may have the potential as a digital twin to enable personalized AAA monitoring.

Vitamin D as a Modifiable Risk Factor for Juvenile Idiopathic Arthritis: A Systematic Review and Meta-analysis of Observational Studies Comparing Baseline Vitamin D in Children with JIA to Individuals Without.

The varying interactions contributing to the development of juvenile idiopathic arthritis (JIA) drive the struggle to understand its etiology. Among the environmental risk factors, vitamin D has been posited to have a component in disease progression, acting as an inflammatory mediator. To investigate the correlation between serum 25-hydroxyvitamin D [25(OH)D] levels, indicative of vitamin D, among patients diagnosed with JIA compared with control participants. The aim was to elucidate potential therapeutic implications of vitamin D in the management of JIA. A systematic search of 6 electronic databases (MEDLINE, Embase, Scopus, CINAHL, Web of Science, and Cochrane Library) was performed until February 2023. Inclusion criteria required participants to be <16 years old (either clinically diagnosed with JIA or a matched control participant), with vitamin D levels measured through serum laboratory methods. Exclusion criteria omitted studies in which participants used vitamin D supplementation or medications affecting vitamin D levels without corresponding statistical analyses on their association with vitamin D levels. Each article was reviewed by at least 2 independent reviewers to assess eligibility for analysis. Data were qualitatively analyzed to compare means of serum 25(OH)D levels (ng/mL) between patients with JIA and control participants, followed by a meta-analysis to obtain effect size. Ten eligible studies were included qualitatively, and eight were included in the meta-analysis. Seven studies found a statistically significant difference in vitamin D levels between control participants and patients with JIA, with five of these reporting a lower mean vitamin D level in patients with JIA. A random-effects model using standardized mean difference found a statistically significant difference in vitamin D levels between control participants and patients with JIA (-0.49; 95% CI, -0.92 to -0.06). The findings from the analysis indicate vitamin D levels were lower in patients with JIA as compared with healthy control participants at baseline. It is recommended that research into vitamin D supplementation and JIA should be conducted.

Burden of vaccine-preventable diseases in adults (50+) in the United States: a retrospective claims analysis

BackgroundIn adults aged 50 + years, vaccine-preventable diseases (VPDs) pose a significant health burden and can lead to additional ‘downstream effects’ of infection beyond the acute phase e.g., increasing the risk for non-communicable disease and exacerbating chronic conditions. The aim was to understand and quantify the burden of VPD downstream effects in hospitalised adults in the United States.MethodsThis retrospective observational study analysed hospitalisation claims data (2016–2019) with 1-year follow-up, in adults with a VPD diagnosis versus matched controls (using Optum’s de-identified Clinformatics Data Mart Database). Outcomes included mortality; increase in Charlson Comorbidity Index (CCI) score; new diagnosis of comorbidities; and loss of independence (defined by need for home health/home care and/or move to long-term facility).ResultsMortality was significantly increased in VPD cases versus controls at 30-day (risk ratio [RR] of 4.08 [95% CI 3.98–4.18]) and 1-year follow-up (RR 2.76 [2.73–2.80]). Over a 1-year follow-up period, morbidity increased following VPD hospitalisation: 65–86% of VPD cases had new comorbidities diagnosed (versus 13–41% of controls); with a significantly higher mean increase in CCI score versus baseline (3.23 in VPD cases versus 0.89 in controls, p < 0.001). Adults were observed to experience a worsening of their health status and were less likely to return to their original health state. In addition, 41% of VPD cases had a loss of independence following hospitalisation versus 12% of controls; as seen by an increased need for home assistance (in 25% versus 9% of controls) and/or a move to a long-term care facility (in 29% versus 6% of controls).ConclusionsThis analysis suggests that VPD hospitalised cases suffer significantly worse clinical outcomes than controls, with downstream effects that include increased mortality and morbidity, and greater loss of independence. Evidence on potential downstream effects of infection is relatively new, and this additional burden is generally not considered in vaccine decision-making. More research is needed to disentangle the effect of VPDs on new comorbidities versus the natural course of the condition. Increasing awareness among adults, healthcare providers and decision makers could help to increase adult vaccination coverage, and reduce the clinical burden of VPDs.

Impact of moderate aerobic exercise on small-world topology and characteristics of brain networks after sport-related concussion: an exploratory study

Sport-related concussion (SRC) is a complex brain injury. By applying graph-theoretical analysis to networks derived from neuroimaging techniques, studies have shown that despite an overall retention of small-world topology, changes in small-world properties occur after brain injury. Less is known about how exercise during athletes’ return to sport (RTS) influences these brain network properties. Therefore, in the present study dense electroencephalography (EEG) datasets were collected pre- and post-moderate aerobic exercise. Small-world properties of whole brain (WB) and the default mode network (DMN) were extracted from the EEG datasets of 21 concussed athletes and 21 healthy matched controls. More specifically, path length (LP), clustering coefficient (CP), and small-world index (SWI) in binary and weighted graphs were calculated in the alpha frequency band (7–13 Hz). Pre-exercise, SRC athletes had higher DMN-CP values compared to controls, while post-exercise SRC athletes had higher WB-LP compared to controls. Weighted WB analysis revealed a significant association between SRC and the absence of small-world topology (SWI ≤ 1) post-exercise. This explorative study provides preliminary evidence that moderate aerobic exercise during athletes’ RTS induces an altered network response. Furthermore, this altered response may be related to the clinical characteristics of the SRC athlete.

Longitudinal weight and plantar pressure distribution while standing after tibial or malleolar fractures in patients with or without fracture union

Fracture healing is usually monitored by clinical impressions and radiographs. Objective and easy methods for assessing fracture healing without radiation would be beneficial. The aim of this study was to analyse whether weight and plantar pressure while standing can be used to monitor healing of tibial or malleolar fractures and whether these parameters can discriminate between patients with and without union. Thirteen patients were longitudinally assessed during each postoperative clinical visit, of whom two developed a nonunion. Eleven matched healthy controls were assessed once. Additionally, five patients already experiencing nonunion were assessed once at the time of their nonunion diagnosis. All participants performed a standing task for ten seconds with pressure-sensing insoles. Greatest improvements were detected throughout the first three months in patients with union. However, six months after surgery, more than half of the parameters were still significantly different from those of the controls. The weight and pressure distributions did not differ between patients with or without union six months after surgery. A standing task can be used to monitor improvements in weight and pressure distribution throughout the healing process of tibial or malleolar fractures, but lacks potential to discriminate between patients with or without fracture union.

Attention and nocebo hyperalgesia: Testing a novel virtual reality attention bias modification paradigm

Nocebo effects in pain (nocebo hyperalgesia) have received significant attention recently, with negative expectancies and anxiety proposed to be explanatory factors. While both expectancy and anxiety can bias attention, attention has been rarely explored as a potential mechanism involved in nocebo hyperalgesia. The present study aimed to explore whether attention bias modification (ABM) using an immersive, ecologically valid VR paradigm successfully induced attention biases (AB) and subsequently influenced nocebo hyperalgesia. One-hundred and two healthy participants were randomised in a 2 (AB training: towards vs. away from pain) x 2 (nocebo condition: nocebo vs. control) design. Pain-related AB was successfully changed by the VR paradigm as measured by reaction time and gaze, with moderate to large effects. Participants then completed either a nocebo instruction and conditioning procedure (nocebo paradigm) or a matched control procedure. The primary outcome was self-reported pain intensity. Secondary outcomes were attention bias and self-reports of expectancy, anticipatory anxiety, and state anxiety. The nocebo paradigm induced significantly greater pain expectancy, anticipatory anxiety and pain intensity during the test phase for the nocebo group compared to control. Pain expectancy also fully mediated the effect of the nocebo group on nocebo hyperalgesia and anticipatory anxiety in separate models. ABM did not, however, affect nocebo hyperalgesia or pain expectancy, casting doubt on the potential for ABM to inoculate against nocebo hyperalgesia. Unexpected effects of ABM were observed for state anxiety and anticipatory anxiety, whereby training away from pain exacerbated each, which necessitates further exploration. PerspectiveThis article tests the efficacy of a novel attention bias modification paradigm, designed in virtual reality, for inducing pain-related biases, and whether these biases exacerbate or inoculate against nocebo hyperalgesia. While pain-related biases were successfully induced, there was no relationship with the strength of induced nocebo hyperalgesia.

Phenotype in Individuals with Heterozygous Rare Variants in LIPC Encoding Hepatic Lipase

Hepatic lipase deficiency is a rare genetic condition caused by biallelic loss-of-function variants in the LIPC gene encoding hepatic lipase. These variants reduce or abolish the protein’s lipolytic activity, resulting in elevated plasma lipids. The condition is classified as autosomal recessive, since dyslipidemia is inconsistently observed in heterozygous patients with only one LIPC variant. However, this has been concluded from historical studies encompassing a few families and having very small sample sizes. Here, we conduct a retrospective chart review of 46 heterozygous subjects, each harboring one rare pathogenic LIPC variant. We compare plasma levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and apolipoprotein B to those of matched controls without LIPC variants. Variant pathogenicity is classified according to the guidelines of the American College of Medical Genetics and Genomics. We observe that levels of total cholesterol, LDL-C, and triglycerides are significantly elevated in the LIPC variant heterozygotes, but HDL-C and apolipoprotein B are not. When filtering solely with respect to pathogenic or likely pathogenic variants, all lipid variables emerge as significantly elevated compared to controls. Thus, hepatic lipase deficiency may not necessarily be a recessive condition, but perhaps semi-dominant since individuals with one variant are phenotypically distinct from the controls. These hypothesis-generating findings regarding LIPC genetic variations observed in a clinical cohort should be evaluated in larger populations and databases.

The Critical Shoulder Angle as a Highly Specific Predictor of a Full-Thickness Rotator Cuff Tear: A Case-Control Study.

The critical shoulder angle (CSA) has become an important topic of study in patients with rotator cuff tears (RCTs). However, there are conflicting data on whether the CSA can differentiate between patients with normal shoulder pathology and full-thickness RCTs on shoulder radiographs. The purpose of this study was to define the relationship between full-thickness RCTs and the CSA. It was hypothesized that patients with full-thickness RCTs would have an increased CSA compared with matched controls. Cross-sectional study; Level of evidence, 3. This retrospective case-control study identified patients with magnetic resonance imaging scans showing full-thickness RCTs between 2009 and 2019. A 1 to 1 propensity score match was performed to identify a control group with normal rotator cuffs while controlling for baseline participant characteristics-including age, sex, body mass index, and tobacco use. A total cohort of 532 was identified, with 266 cases and 266 controls. Two independent observers measured CSAs on true anteroposterior shoulder radiographs. There was no difference in baseline participant characteristics between the RCT and the non-RCT groups (P > .05). The mean CSA for the entire cohort was 33.6°± 4.2°. The CSA did not significantly vary by sex (P = .088) or tobacco usage (P = .16). The mean CSA for the RCT case group, 36.2°± 3.3°, was significantly different from the mean CSA for the control group, 30.9°± 3.3° (P < .0001). The receiver operating characteristic curve analysis produced an area under the curve of 0.88 (P < .0001). At CSAs ≥35°, there was a 67.7% sensitivity and 89.4% specificity for having a full-thickness RCT. Last, each degree of increase in the CSA increased the risk of having an associated RCT by 1.7 times (OR, 1.7 [95% CI, 1.551-1.852]; P < .0001). Patients with RCTs had significantly higher CSAs compared with matched controls. Increased CSA was an independent risk factor for RCTs, with an odds ratio of 1.7 per degree. The CSA is an accurate test (area under the curve, 0.88) with good sensitivity (67.7%) and specificity (89.4%) at values ≥35°. The CSA is a simple, reproducible measurement that can assist in clinical decision-making regarding full-thickness RCTs.

Incidence, Risk Factors, and Functional Outcomes of Symptomatic Postoperative Spinal Epidural Hematoma: Case-Control Study.

Symptomatic postoperative spinal epidural hematomas (PEDHs) are rare complications with significant implications on patients' functional outcomes. Strategies for PEDH prevention are poorly understood. This study sought to evaluate preoperative and intraoperative variables predicting the risk of PEDH, and patients' functional outcomes after PEDH evacuation. This is a single institution study of all PEDH cases requiring a reoperation and matched controls over six year period. The incidence of PEDH was calculated by region and operative technique. The preoperative and intraoperative parameters of 40 cases and 40 matched controls were compared. 5,941 spine surgeries and 40 symptomatic PEDH cases requiring reoperation were identified (0.67% overall incidence). The highest incidence of PEDH was observed after minimally invasive lumbar laminectomimes. Higher preoperative diastolic blood pressure was a risk factor for PEDH. Of the 17 PEDH cases that had a drain placed at the time of index surgery, 8 patients (47%) still had the drain in place at the time of diagnosis of PEDH. Among the posterior index approaches, 18 cases (51.43%), one cervicothoracic and seventeen lumbar, did not develop paresis at the time of PEDH diagnosis. 17 cases (48.57%), nine cervicothoracic and eight lumbar, developed paresis. Ten of the patients with paresis had complete resolution of motor weakness, while seven never achieved complete resolution. While the incidence of PEDH was below one percent, nearly half of the patients developed motor weakness as a presenting symptom and a third of the patients never had resolution of the weakness.