Influence of multimorbidity and socioeconomic position on long-term healthcare utilization and prognosis in patients after cardiac resynchronization therapy implantation.

Aims: We aimed to investigate the influence of socioeconomic position (SEP) and multimorbidity on cross-sectional healthcare utilization and prognosis in patients after cardiac resynchronization therapy (CRT) implantation. Methods and results: We included first-time CRT recipients with left ventricular ejection fraction ≤35% implanted between 2000 and 2017. Data on chronic conditions, use of healthcare services, and demographics were obtained from Danish national administrative and health registries. Healthcare utilization (in- and outpatient hospitalizations, activities in general practice) was compared by multimorbidity categories and SEP by using a negative binomial regression model. The association between SEP, multimorbidity, and prognostic outcomes was analysed using Cox proportional hazards regression. We followed 2007 patients (median age of 70 years), 79% were male, 75% were on early retirement or state pension, 37% were living alone, and 41% had low education level for a median of 5.2 [inter-quartile range: 2.2-7.3) years. In adjusted regression models, a higher number of chronic conditions were associated with increased healthcare utilization. Both cardiovascular and non-cardiovascular hospital contacts were increased. Patients with low SEP had a higher number of chronic conditions, but SEP had limited influence on healthcare utilization. Patients living alone and those with low educational level had a trend towards a higher risk of all-cause mortality [adjusted hazard ratio (aHR): 1.17, 95% confidence interval (CI) 1.03-1.33, and aHR 1.09, 95% CI 0.96-1.24). Conclusion: Multimorbidity increased the use of cross-sectional healthcare services, whereas low SEP had minor influence on the utilizations. Living alone and low educational level showed a trend towards a higher risk of mortality after CRT implantation.

Employment Status Following Heart Transplantation: Data From the Danish Nationwide Social Service Payment Register During 20 years.

Most studies on vocational rehabilitation after heart transplantation (HTX) are based on self-reported data. Danish registries include weekly longitudinal information on all public transfer payments. We intended to describe 20-year trends in employment status for the Danish heart-transplant recipients, and examine the influence of multimorbidity and socioeconomic position (SEP). Linking registry and Scandiatransplant data (1994-2018), we conducted a study in recipients of working age (19-63 years). The cohort contained 492 recipients (79% males) and the median (IQR) age was 52 years (43-57 years). Five years after HTX, 30% of the survived recipients participated on the labor market; 9% were in a flexible job with reduced health-related working capacity. Moreover, 60% were retired and 10% eligible for labor market participation were unemployed. Recipients with multimorbidity had a higher age and a lower prevalence of employment. Five years after HTX, characteristics of recipients with labor market participation were: living alone (27%) versus cohabitation (73%); low (36%) versus medium-high (64%) educational level; low (13%) or medium-high (87%) income group. Heart-transplant recipients with multimorbidity have a higher age and a lower prevalence of employment. Socioeconomically disadvantaged recipients had a lower prevalence of labor market participation, despite being younger compared with the socioeconomically advantaged.

Association between socioeconomic position and discontinuation of pharmacotherapy for heart failure after cardiac resynchronization therapy.

AIMS: Pharmacological therapy remains a cornerstone in heart failure (HF) treatment despite implantation of a cardiac resynchronization therapy (CRT) device. The aim of this study was to investigate the association between 1) drug discontinuation, and 2) long-term adherence to HF pharmacotherapy after CRT implantation and socioeconomic position and multimorbidity. METHODS AND RESULTS: We conducted a registry-based cohort study including all patients who underwent a first-time CRT implantation at Aarhus University Hospital from 2000-2017. HF pharmacotherapy included beta blockers (BBs), renin angiotensin system inhibitors (ACEI/ARB), and mineralocorticoid receptor antagonists (MRAs). Patients were identified using the Danish Pacemaker and ICD Registry, and information about medication and comorbidities was obtained through linkage to the Danish health registries. We identified 2,007 patients of whom 1,880 (94%) were eligible for inclusion. The cumulative incidence of drug discontinuation at 10 years was 6% (95% confidence interval [CI] 5-8%) for BB, 10% (95% CI 9-12%) for ACEI/ARB, and 24% (95% CI 20-27%) for MRAs. Living alone was associated with higher BB discontinuation rates (hazard ratio [HR] 1.83, 95%CI 1.20-2.79), whereas patients with multimorbidity were more likely to discontinue ACEI/ARB- (HR 1.92, 95%CI 1.33-2.80) and MRA therapy (HR 1.51, 95% CI 1.10-2.09). Income- and educational level did not influence drug discontinuation rates, and similar adherence patterns were observed across all strata of socioeconomic position and multimorbidity. CONCLUSION: In patients with CRTs, drug discontinuation rates were low, and adherence to HF pharmacotherapy was comparable regardless of socioeconomic position. Living alone and multimorbidity were associated with discontinuation of specific HF drugs.

Socio-economic position, multimorbidity, and health care utilization among Danish left ventricular assist device patients.

AIMS: Increasing numbers of patients with advanced heart failure and significant comorbidity and social barriers are considered for left ventricular assist devices (LVADs). We sought to examine health care utilization post-LVAD implantation, including the influence of individual-level socio-economic position and multimorbidity. METHODS AND RESULTS: We conducted a Danish nationwide cohort study linking individual-level data from clinical LVAD databases, the Scandiatransplant Database, and Danish national medical and administrative registries. Socio-economic position included cohabitation status, educational level, and employment status. Multimorbidity was defined as two or more chronic conditions from at least two chronic disease groups. Health care utilization (hospital activity, general practice activity, and redeemed medical prescriptions) within 2 years post-discharge after LVAD implantation was evaluated using descriptive statistics at 0.5 year intervals. We identified 119 patients discharged alive with first-time LVAD implanted between 2006 and 2018. The median age of the patients was 56.1 years, and 88.2% were male. Patients were followed until heart transplantation, LVAD explantation, death, 31 December 2018, or for 2 years. The median follow-up was 0.8 years. The highest median use of health care services was observed 0-0.5 years post-LVAD discharge compared with the subsequent follow-up intervals: 0.5-1, 1-1.5, and 1.5-2 years, respectively. The median (interquartile range) number of hospitalizations was 10 (7-14), bed days 14 (9-28), outpatient visits 8 (5-12), telephone contacts with a general practitioner 4 (2-8), and total redeemed medical prescriptions 26 (19-37) within 0-0.5 years post-LVAD discharge compared with the median utilization within the consecutive follow-up periods [e.g. within 0.5-1 year: hospitalizations 5 (3-8), bed days 8 (4-14), outpatient visits 5 (3-8), telephone contacts 2 (0-5), and redeemed medical prescriptions 24 (18-30)]. The median use of health care services was stable from 0.5 years onwards. The median number of hospitalizations and bed days was slightly higher in patients living alone with a low educational level or low employment status within 0-0.5 years post-LVAD implantation. Finally, the median number of in-hospital days and redeemed prescriptions was higher among patients with pre-existing multimorbidity. CONCLUSIONS: Among patients who underwent LVAD implantation, health care utilization was high in the early post-LVAD discharge phase and was influenced by socio-economic position. Multimorbidity influenced the number of in-hospital days and redeemed prescriptions during the 2 year follow-up.

Adherence to Pharmacotherapies After Heart Transplantation in Relation to Multimorbidity and Socioeconomic Position: A Nationwide Register-Based Study.

No studies have examined the impact of multimorbidity and socioeconomic position (SEP) on adherence to the pharmacological therapies following heart transplantation (HTx). Using nationwide Danish registers, we tested the hypothesis that multimorbidity and SEP affect treatment patterns and adherence to pharmacological therapies in first-time HTx recipients. Pharmacological management included cost-free immunosuppressants and adjuvant medical treatment (preventive and hypertensive pharmacotherapies; loop diuretics). We enrolled 512 recipients. The median (IQR) age was 51 years (38-58 years) and 393 recipients (77%) were males. In recipients with at least two chronic diseases, prevalence of treatment with antihypertensive pharmacotherapies and loop diuretics was higher. The overall prevalence of adherence to treatment with tacrolimus or mycophenolate mofetil was at least 80%. Prevalence of adherence to preventive pharmacotherapies ranged between 65% and 95% and between 66% and 88% for antihypertensive pharmacotherapies and loop diuretics, respectively. In socioeconomically disadvantaged recipients, both the number of recipients treated with and adherence to cost-free everolimus, lipid modifying agents, angiotensin-converting enzyme/angiotensin II inhibitors, calcium channel blockers, and loop diuretics were lower. In recipients with multimorbidity, prevalence of treatment with antihypertensive pharmacotherapies and loop diuretics was higher. Among socioeconomically disadvantaged recipients, both number of patients treated with and adherence to cost-free everolimus and adjuvant pharmacotherapies were lower.

Long-Term Medical Treatment and Adherence in Patients With Left Ventricular Assist Devices: A Danish Nationwide Cohort Study.

The use of a left ventricular assist device (LVAD) in treating advanced heart failure has increased. However, data regarding medical treatment and adherence following LVAD implantation is sparse, particularly whether socioeconomic factors (cohabitation status, educational level, employment status, and income) and multimorbidity influence these aspects, which are known to impact adherence in heart failure patients. We performed a nationwide cohort study of 119 patients with LVAD implanted between January 1, 2006, and December 31, 2018, who were discharged alive with LVAD therapy. We linked individual-level data from clinical LVAD databases, the Scandiatransplant Database, and Danish medical and administrative registers. Medical treatment 90-day pre-LVAD and 720-day post-LVAD were assessed using descriptive statistics in 90-day intervals. Medication adherence (proportion of days covered ≥80%) was assessed 181- to 720-day post-LVAD. The proportions of patients using angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (88.7%), beta-blockers (67.0%), mineralocorticoid receptor antagonists (62.9%), warfarin (87.6%), and aspirin (55.7%) within 90-day post-LVAD were higher than pre-LVAD and were stable during follow-up. Medication adherence ranged from 86.7% (aspirin) to 97.8% (warfarin). Socioeconomic factors and multimorbidity did not influence medical medication use and adherence. Among LVAD patients, medical treatment and adherence are at high levels, regardless of socioeconomic background and multimorbidity.

The Influence of Reduced Graphene Oxide on the Texture and Chemistry of N,S-Doped Porous Carbon. Implications for Electrocatalytic and Energy Storage Applications.

In this work, we study the influence of reduced graphene oxide (rGO) on the morphology and chemistry of highly porous N,S-doped carbon cryogels. Simultaneously, we propose an easily upscalable route to prepare such carbons by adding graphene oxide (GO) in as-received suspended form to the aqueous solution of the ι-carrageenan and urea precursors. First, 1.25-5 wt% GO was incorporated into the dual-doped polymer matrix. The CO2, CO, and H2O emitted during the thermal treatments resulted in the multifaceted modification of the textural and chemical properties of the porous carbon. This facilitated the formation of micropores through self-activation and resulted in a substantial increase in the apparent surface area (up to 1780 m2/g) and pore volume (up to 1.72 cm3/g). However, adding 5 wt% GO led to overactivation. The incorporated rGO has an ordering effect on the carbon matrix. The evolving oxidative species influence the surface chemistry in a complex way, but sufficient N and S atoms (ca. 4 and >1 at%, respectively) were preserved in addition to the large number of developing defects. Despite the complexity of the textural and chemical changes, rGO increased the electrical conductivity monotonically. In alkaline oxygen reduction reaction (ORR) tests, the sample with 1.25 wt% GO exhibited a 4e- mechanism and reasonable stability, but a higher rGO content gradually compromised the performance of the electrodes. The sample containing 5 wt% GO was the most sensitive under oxidative conditions, but after stabilization it exhibited the highest gravimetric capacitance. In Li-ion battery tests, the coulombic efficiency of all the samples was consistently above 98%, indicating the high potential of these carbons for efficient Li-ion insertion and reinsertion during the charge-discharge process, thereby providing a promising alternative for graphite-based anodes. The cell from the 1.25 wt% GO sample showed an initial discharge capacity of 313 mAh/g, 95.1% capacity retention, and 99.3% coulombic efficiency after 50 charge-discharge cycles.

Dual-Role Peptide with Capping and Cleavage Site Motifs in Nanoparticle-Based One-Pot Colorimetric and Electrochemical Protease Assay.

A new method for enzyme substrate assembly and its use in proteolytic enzyme assays with colorimetric and electrochemical detection is presented. The novelty of the method is the use of dual-function synthetic peptide containing both gold clustering and protease-sensitive moieties, which not only induces the simple formation of the peptide-decorated gold nanoparticle test substrates but also allows for the detection of proteolysis in the same batch. Protease-treated nanoparticles with a destabilized peptide shell became more prone to electroactivity, and thus, the model enzyme plasmin activity could be quantified with stripping square wave voltammetry analysis as well, giving an alternative method to conduct aggregation-based assays. Spectrophotometric and electrochemical calibration data proved to be linear within the 40-100 nM active enzyme concentration range, with possible extensions of the dynamic range by varying substrate concentration. The simple initial components and the ease of synthesis make the assay substrate preparation economic and easy to implement. The possibility of cross-check analytical results with two independent measurement techniques in the same batch greatly increases the applicability of the proposed system.

Individual-Level Socioeconomic Position and Long-Term Prognosis in Danish Heart-Transplant Recipients.

Socioeconomic deprivation can limit access to healthcare. Important gaps persist in the understanding of how individual indicators of socioeconomic disadvantage may affect clinical outcomes after heart transplantation. We sought to examine the impact of individual-level socioeconomic position (SEP) on prognosis of heart-transplant recipients. A population-based study including all Danish first-time heart-transplant recipients (n = 649) was conducted. Data were linked across complete national health registers. Associations were evaluated between SEP and all-cause mortality and first-time major adverse cardiovascular event (MACE) during follow-up periods. The half-time survival was 15.6 years (20-year period). In total, 330 (51%) of recipients experienced a first-time cardiovascular event and the most frequent was graft failure (42%). Both acute myocardial infarction and cardiac arrest occurred in ≤5 of recipients. Low educational level was associated with increased all-cause mortality 10-20 years post-transplant (adjusted hazard ratio [HR] 1.95, 95% confidence interval [CI] 1.19-3.19). During 1-10 years post-transplant, low educational level (adjusted HR 1.66, 95% CI 1.14-2.43) and low income (adjusted HR 1.81, 95% CI 1.02-3.22) were associated with a first-time MACE. In a country with free access to multidisciplinary team management, low levels of education and income were associated with a poorer prognosis after heart transplantation.

Maternal Smoking During Pregnancy and Risk of Appendicitis in the Offspring.

BACKGROUND: Existing evidence on the link between smoking and appendicitis is scarce and ambiguous. We therefore conducted a population-based cohort study in Denmark to investigate whether smoking during pregnancy is associated with an increased risk of appendicitis in offspring. METHODS: We used the Danish Birth Registry to include all singletons born during 1991-2017 and to identify maternal smoking status during pregnancy. We followed the children from birth until date of appendicitis, emigration, death, or administrative end of study (31 December 2018), whichever came first. We calculated crude and adjusted hazard ratios (HRs) of appendicitis with 95% confidence intervals (CIs) comparing children of mothers who smoked during pregnancy to children of nonsmokers. Further, we conducted a bias analysis and sibling analysis. RESULTS: We included 1,659,526 singletons of whom 19% were born to mothers who smoked during pregnancy. After maximum 28 years of follow-up, hazard rates for children of smokers were slightly higher than for children of nonsmokers [adjusted HR: 1.07 (95% CI = 1.04, 1.10)]. Stratification by sex revealed no association for males [adjusted HR: 1.02 (95% CI = 0.99, 1.06)], but a higher HR for females [adjusted HR: 1.13 (95% CI = 1.09, 1.18)]. This association increased with increasing length of follow-up, indicating that the association may be mediated by later-life exposures. The bias analysis indicated that misclassification of maternal smoking could attenuate a true association, while the sibling analysis showed no association. CONCLUSIONS: Maternal smoking during pregnancy and appendicitis in the offspring may be associated.

Influence of multimorbidity and socioeconomic factors on long-term cross-sectional health care service utilization in heart transplant recipients: A Danish cohort study.

BACKGROUND: Survival after heart transplantation has increased due to continuously refined and effective care management. Knowledge is sparse on the influence of multimorbidity and social vulnerability on management. We assessed the long-term influence of multimorbidity and socioeconomic factors on cross-sectional health care service utilization in heart transplant recipients. METHODS: First-time heart transplant recipients, from the Transplant Center at Aarhus University Hospital, were followed from transplant until December 31, 2018. We linked individual-level data from the Scandiatransplant Database to Danish national registers. We followed recipients for 15 years using descriptive statistic. RESULTS: We identified 325 recipients; 79% were male and 60% were between 41 and 60 years of age. The median (IQR) number of chronic conditions at baseline was 1.0 (1.0-2.0). The prevalence of recipients with ≥3 chronic conditions in the follow-up period 0 to 1 year was 10% and 65% within 10 to 15 years. The median use of cross-sectional health care services was higher in recipients with ≥3 chronic conditions compared to <3 chronic conditions during follow-up intervals. The median utilization of hospital outpatient visits and consultations in general practice were higher in recipients with low educational level, low employment status, or low income, respectively. We observed lower median number of redeemed prescriptions for medical therapies in recipients living alone or within the lowest income group. CONCLUSIONS: The use of cross-sectional health care services was higher in heart transplant recipients with increased incidence of comorbidities during follow-up intervals. A socioeconomic influence was observed in the utilization of services.

Biomass Related Highly Porous Metal Free Carbon for Gas Storage and Electrocatalytic Applications.

In this paper we report the synthesis of a N, S co-doped metal free carbon cryogel obtained from a marine biomass derived precursor using urea as nitrogen source. Natural carrageenan intrinsically contains S and inorganic salt. The latter also serves as an activating agent during the pyrolytic step. The overall 11.6 atomic % surface heteroatom concentration comprises 5% O, 4.6% N and 1% S. The purified and annealed final carbon (CA) has a hierarchical pore structure of micro-, meso- and macropores with an apparent surface area of 1070 m2/g. No further treatment was applied. The gas adsorption potential of the samples was probed with H2, CO2 and CH4, while the electrocatalytic properties were tested in an oxygen reduction reaction. The atmospheric CO2 and CH4 storage capacity at 0 °C in the low pressure range is very similar to that of HKUST-1, with the CO2/CH4 selectivity below 20 bar, even exceeding that of the MOF, indicating the potential of CA in biogas separation. The electrocatalytic behavior was assessed in an aqueous KOH medium. The observed specific gravimetric capacitance 377 F/g was exceeded only in B, N dual doped and/or graphene doped carbons from among metal free electrode materials. The CA electrode displays almost the same performance as a commercial 20 wt% Pt/C electrode. The oxygen reduction reaction (ORR) exhibits the 4-electron mechanism. The 500-cycle preliminary stability test showed only a slight increase of the surface charge.

Statin Initiation and Risk of Amyotrophic Lateral Sclerosis: A Danish Population-based Cohort Study.

BACKGROUND: The evidence of an association between statins and amyotrophic lateral sclerosis (ALS) is heterogeneous and inconclusive. METHODS: We performed a population-based cohort study consisting of 974,304 statin initiators ≥40 years of age and 1,948,606 matched general population comparators identified from Danish, nationwide registries (1996-2016). We computed incidence rates and hazard ratios (HRs) of a first-time hospital-based diagnosis of ALS. HRs were controlled for sex, birth year, calendar year, medically diagnosed comorbidities, and concomitant medications. RESULTS: During a median follow-up of 7.7 years, 852 ALS events occurred among statin initiators (11.3 [95% confidence interval (CI) = 10.6, 12.1] events per 100,000 person-years) and 1,679 among noninitiators (11.4 [95% CI = 10.9, 12.0] events per 100,000 person years). The overall adjusted HR indicated a slight association between statin initiation and ALS (1.11 [95% CI = 1.00, 1.23]. In the first year after initiation, the HR was 1.40 (95% CI = 1.09, 1.79) for both sexes combined, 1.00 (95% CI = 0.70, 1.42) for men, and 1.92 (95% CI = 1.30, 2.82) for women. The associations diminished to approximately null after the first year of follow-up for both sexes combined and for men, but point estimates were above 1 for women until 10 years after initiation. CONCLUSIONS: Statin initiation was largely unassociated with ALS diagnosis but was associated with an elevated risk of ALS in women, especially in the first year after initiation. The association could be explained by reverse causation, detection bias, early neurotoxic effects of statins that affect women more than men, or a combination thereof.

Electric and Photocatalytic Properties of Graphene Oxide Depending on the Degree of Its Reduction.

When graphene oxide is reduced, the functional groups are released and the structure becomes more ordered. The degree of reduction might be tunable with the process parameters. In our work, graphene oxide is prepared and the effect of thermal and chemical reduction is investigated. The samples are characterized with TG/DTA-MS, SEM-EDX, TEM, XPS, ATR-FTIR, Raman spectroscopy and XRD. Their electrical resistance, cyclic voltammetry and photocatalytic activity data are investigated. The conductivity can be varied by several orders of magnitude, offering a tool to match its electrical properties to certain applications. Low temperature reduction in air offers a material with the highest capacitance, which might be used in supercapacitors. The bare graphene oxide has considerably larger photocatalytic activity than P25 TiO2. Reduction decreases the activity, meaning that reduced graphene oxide can be used as an electron sink in composite photocatalysts, but does not contribute to the photocatalytic activity by itself.

Water-Ionic Liquid Binary Mixture Tailored Resorcinol-Formaldehyde Carbon Aerogels without Added Catalyst.

The potential applications of mesoporous carbon aerogels are wide-ranging. These gels are often obtained from resorcinol-formaldehyde (RF) hydrogel precursors. The sol-gel method in this synthesis provides an efficient and versatile means of product control through systematic variation of process conditions, such as pH, stoichiometry, concentration, catalyst, further additives, etc., in addition to the drying and pyrolytic conditions. Here, a novel means of tuning the texture of carbon aerogels is proposed. Water-1-ethyl-3-methylimidazolium ethyl sulfate ([emim][EtSO4] mixtures constitutes a polycondensation medium that requires no added catalyst, thus yielding an intrinsically metal-free carbon aerogel after pyrolysis. We also show that the carbon morphology is tailored by the supramolecular structure of the aqueous ionic liquid. The results of scanning electron micrographs, low-temperature nitrogen adsorption/desorption isotherms, and small-angle X-ray scattering (SAXS) confirm that changing the initial water concentration from 9 to 55 wt % gives rise to systematic alteration of the mesopore size and volume, as well as of the bead size. The pore structure becomes consolidated only when the water content exceeds 25 wt %. When the water content reaches 55 wt %, the bead size increases by two orders of magnitude. The electrocatalytic performance, however, is compromised, most probably by structural defects.

Durability of high surface area platinum deposits on microelectrode arrays for acute neural recordings.

The durability of high surface area platinum electrodes during acute intracerebral measurements was investigated. Electrode sites with extremely rough surfaces were realized using electrochemical deposition of platinum onto silicon-based microelectrode arrays from a lead-free platinizing solution. The close to 1000-fold increase in effective surface area lowered impedance, its absolute value at 1 kHz became about 7 and 18 % of the original Pt electrodes in vitro and in vivo, respectively. 24-channel probes were subjected to 12 recording sessions, during which they were implanted into the cerebrum of rats. Our results showed that although on the average the effective surface area of the platinized sites decreased, it remained more than two orders of magnitude higher than the average effective surface area of the original, sputtered thin-film platinum electrodes. Sites with electrochemical deposits proved to be superior, e.g. they provided less thermal and 50 Hz noise, even after 12 penetrations into the intact rat brain.