Chronic Treatment Research Articles

Cardiopulmonary Response to Acute Exercise before Hemodialysis: A Pilot Study.

Disparities in physical fitness between immediately before dialysis (pre-D) and the day following dialysis (non-D) have not been investigated despite potential adverse factors such as fluid status, uremia, and electrolyte levels in the pre-dialysis period. The effect of acute exercise immediately before hemodialysis (HD) on HD-related hypotension remains unclear. We hypothesized that cardiopulmonary performance and muscular strength would be inferior in the immediate pre-D period compared to those non-D. Twenty patients receiving chronic HD treatments underwent symptom-limited incremental cardiopulmonary exercise testing (CPET) and isokinetic testing both 1-2 h prior to dialysis (pre-D) and non-D. This investigation was a sub-study of a clinical trial assessing the efficacy of a pre-D exercise training program. Blood pressure profiles during HD post-CPET and pre-D exercise training were compared with those during usual HD sessions. No adverse events were observed during the 80 exercise tests. Prior to dialysis, the nadir of the ventilatory equivalent of CO2 was slightly elevated, the resting heart rate was lower, and the peak systolic blood pressure was higher than those non-D. Contrary to our hypothesis, peak <inline-formula><mml:math id="m1" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mover accent="true"><mml:mi mathvariant="normal">V</mml:mi><mml:mo>˙</mml:mo></mml:mover><mml:msub><mml:mi mathvariant="normal">O</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:mrow></mml:math></inline-formula> and quadriceps peak torque showed no differences. Blood pressure profiles during HD post-exercise were similar to those during sessions without prior exercise, except for a lower resting systolic blood pressure at the beginning of HD. Cardiopulmonary response and muscular strength in the 1-2 h prior to HD were comparable with those on the day following HD, with only minor clinically insignificant differences. Acute exercise prior to HD did not affect the magnitude of hypotension during HD. This study suggests a potential alternative timing for exercise training or testing in patients undergoing chronic HD.

Temperature-responsive self-contraction nanofiber/hydrogel composite dressing facilitates the healing of diabetic-infected wounds

Bacterial infections and long-term inflammation cause serious secondary damage to chronic diabetic wounds and hinder the wound healing processes. Currently, multifunctional hydrogels have shown promising effects in chronic wound repair. However, traditional hydrogels only keep the wound moist and protect it from bacterial infection, and cannot provide mechanical force to contract the wound edges to achieve facilitated wound closure. Here, an asymmetric composite dressing was created by combining biaxially oriented nanofibers and hydrogel, inspired by the double-layer structure of the traditional Chinese medicinal plaster patch, for managing chronic wounds. Specifically, electrospun Poly-(lactic acid-co-trimethylene carbonate) (PLATMC) nanofibers and methacrylate gelatin (GelMa) hydrogel loaded with Epinecidin-1@chitosan (Epi-1@CS) nanoparticles are assembled as the temperature-responsive self-contracting nanofiber/hydrogel (TSNH) composite dressing. The substrate layer of PLATMC nanofibers combines topological morphology with material properties to drive wound closure through temperature-triggered contraction force. The functional layer of GelMa hydrogel is loaded with Epi-1@CS nanoparticles that combine satisfactory cytocompatibility, and antioxidant, anti-inflammatory, and antibacterial properties. Strikingly, in vivo, the TSNH dressing could regulate the diabetic wound microenvironment, thereby promoting collagen deposition, facilitating angiogenesis, and reducing the inflammatory response, which promotes the rapid healing of chronic wounds. This study highlights the potential of synergizing mechanical and biochemical signals in enhancing chronic wound treatment. Overall, this TSNH composite dressing is provided as a reliable approach to solving the long-standing problem of chronically infected wound healing.

Exploring the impact of subjective well-being on medication adherence: A cross-sectional study among individuals with multiple chronic diseases

BackgroundMedication non-adherence is a significant barrier to optimal treatment goals. The study explores the association between subjective well-being (SWB) and medication adherence among Lebanese individuals with multiple chronic diseases and identifies additional factors that may influence adherence in this population. MethodsAn exploratory, cross-sectional study was conducted for three months at six community pharmacies. Adherence was assessed using the Adherence to Refills and Medication Scale Arabic Lebanese Version (ARMS-A). The SWB was measured using the Arabic Scale of Happiness (ASH), Love of Life Scale (LLS), Arab Hope Scale (AHS), and Satisfaction with Life Scale (SWLS). Spearmen's Rho correlation analyzed the association between ARMS-A and SWB constructs. Binary logistic regression identified predictors of adherence among individuals with chronic diseases and on multiple chronic medications. ResultsOf 400 participants, 106 (26.5 %) with a 95 % CI, 0.22–0.31, were adherent. Lower medication adherence (reflected in higher ARMS-A scores) was associated with lower SWB (p = 0.01). Multivariate analysis showed that lower education (OR=2.21, 95 % CI, 1.01–4.81), lack of a specific diet (OR = 1.64, 95 % CI, 1.01–2.69), and frequent hospital and/or emergency visits (OR=3.29, 95 % CI, 1.75–6.17 for 2 visits; OR = 2.71, 95 % CI, 1.43–5.14 for ≥3 visits) significantly increased the odds of non-adherence to chronic treatment. However, higher income (OR = 0.06, 95 % CI, 0.01–0.38), healthcare provider occupation (OR = 0.42, 95 % CI, 0.21–0.48), and having diabetes mellitus (OR = 0.59, 95 % CI, 0.36–0.96) correlated with better adherence. ConclusionA significant portion of participants failed to adhere to their prescribed chronic medications, influenced by multicomplex socioeconomic, psychological, and health-related factors. These findings demonstrate the need for culturally-tailored, pharmacist-led interventions to improve medication adherence and overall health outcomes.

Multiple strategies approach: A novel crosslinked hydrogel forming chitosan-based microneedles chemowrap patch loaded with 5-fluorouracil liposomes for chronic wound cancer treatment

Untreated or poorly managed chronic wounds can progress to skin cancer. Topically applied 5-fluorouracil (5-FU), a nonspecific cytostatic agent, can cause various side effects. Its high polarity also results in low cell membrane affinity and bioavailability. Hydrogel, used for its occlusive effect, is one platform for treating chronic wounds combined with PEGylated liposomes (LPs), developed to increase drug-skin affinity. This research aimed to develop a novel hydrogel forming chitosan-based microneedles (HFM) chemowrap patch containing 5-FU PEGylated LPs, improving 5-FU efficiency for pre-carcinogenic and carcinogenic skin lesions. The results indicated that the 5-FU-PEGylated LPs-loaded HFM chemowrap patch exhibited desirable physical and mechanical characteristics with complete penetration ability. Furthermore, in vivo skin permeation studies demonstrated the highest percentage of 5-FU permeated the skin (42.06 ± 11.82 %) and skin deposition (75.90 ± 1.13 %) compared to the other treatments, with demonstrated superior percentages of complete wound healing in in vivo (47.00 ± 5.77 % wound healing at day 7) and in NHF cells (92.79 ± 7.15 % at 48 h). Furthermore, 5-FU-PEGylated LPs-loaded HFM chemowrap patches exhibit efficient anticancer activity while maintaining safety for normal cells. The results also show that the developed formulation of a 5-FU-PEGylated LPs-loaded HFM chemowrap patch could enhance apoptosis higher than that of the 5-FU solution. Consequently, 5-FU PEGylated LPs-loaded HFM chemowrap patch represented a promising drug delivery approach for treating pre-carcinogenic and carcinogenic skin lesions.

Handling false chronic kidney disease and diabetes treatment information.

While examining the social perspectives of chronic kidney disease (CKD) and its most common cause, diabetes, a common problem is spread of misleading information by unqualified people. This concerning trend makes it more difficult for patients to receive prompt and proper medical advice, which in turn further delays their referral to nephrologists and endocrinologists. In this communication, we highlight the challenges and consequences of this burning issue. We also propose the steps that various stakeholders and policy makers should take to contain this issue at the earliest.

Inhibition of Calcineurin with FK506 Reduces Tau Levels and Attenuates Synaptic Impairment Driven by Tau Oligomers in the Hippocampus of Male Mouse Models.

Alzheimer's disease (AD) is the most common age-associated neurodegenerative disorder, characterized by progressive cognitive decline, memory impairment, and structural brain changes, primarily involving Aβ plaques and neurofibrillary tangles of hyperphosphorylated tau protein. Recent research highlights the significance of smaller Aβ and Tau oligomeric aggregates (AβO and TauO, respectively) in synaptic dysfunction and disease progression. Calcineurin (CaN), a key calcium/calmodulin-dependent player in regulating synaptic function in the central nervous system (CNS) is implicated in mediating detrimental effects of AβO on synapses and memory function in AD. This study aims to investigate the specific impact of CaN on both exogenous and endogenous TauO through the acute and chronic inhibition of CaN. We previously demonstrated the protective effect against AD of the immunosuppressant CaN inhibitor, FK506, but its influence on TauO remains unclear. In this study, we explored the short-term effects of acute CaN inhibition on TauO phosphorylation and TauO-induced memory deficits and synaptic dysfunction. Mice received FK506 post-TauO intracerebroventricular injection and TauO levels and phosphorylation were assessed, examining their impact on CaN and GSK-3β. The study investigated FK506 preventive/reversal effects on TauO-induced clustering of CaN and GSK-3β. Memory and synaptic function in TauO-injected mice were evaluated with/without FK506. Chronic FK506 treatment in 3xTgAD mice explored its influence on CaN, Aβ, and Tau levels. This study underscores the significant influence of CaN inhibition on TauO and associated AD pathology, suggesting therapeutic potential in targeting CaN for addressing various aspects of AD onset and progression. These findings provide valuable insights for potential interventions in AD, emphasizing the need for further exploration of CaN-targeted strategies.

A Randomized Trial Evaluating Acceptance and Commitment Therapy and Smart Phone Care Management Application to Augment Buprenorphine Therapy for Opioid Use and Chronic Pain.

There is high comorbidity of opioid use disorder (OUD) and chronic pain (CP), which is often addressed by prescribing buprenorphine (BUP). While BUP is effective in preventing overdose, it does not address the psychological aspects of OUD and CP comorbidity and treatment retention rates are as low as 50%. The Virtual Opioid use disorder Integrated Chronic Pain Treatment (VOICE) study (NCT05039554) is a novel effectiveness-implementation trial to test a 12-week virtual group Acceptance and Commitment Therapy (ACT) protocol and a care management smartphone application (app; Valera Health) on pain and opioid use in patients with OUD and CP receiving BUP. Using a 2 × 2 factorial design, participants (expected N = 280) are randomized into: ACT, Valera app, ACT + Valera, or Treatment as Usual arm. This study is taking place in the Bronx, NY, a racially/ethnically diverse community that faces numerous socioeconomic stressors and is one of the nation's epicenters of the opioid epidemic. We created a culturally responsive ACT group protocol, and Valera psychoeducational material. Outcome measures include NIH HEAL Common Data Elements and ACT and Valera-specific measures. We are conducting a novel 2 × 2 trial investigating augmenting BUP treatment with ACT and Valera, with the goal that improved mental health and access to care will result in decreased and opioid use and pain interference.

Digoxin initiation after an acute heart failure episode and its association with post-discharge outcomes: an international multicenter analysis.

Digoxin is commonly used to treat acute heart failure (AHF), especially in patients with concurrent atrial fibrillation (AF). Nonetheless, there is little consensus about in which patients digoxin should be given, the proper time for digoxin initiation, and whether digoxin initiation is associated with improved outcomes. We investigated factors related to digoxin initiation after an episode of AHF and whether patients receiving digoxin presented better short-term outcomes. We analyzed digoxin-naïve AHF patients from a Spanish and Swiss database, who were dichotomized into cohorts based on their receipt of digoxin treatment at discharge. The relationship between digoxin initiation and 23 additional patient covariates, including chronic treatment, was investigated, as well as its association with 90-day combined adverse events (defined as all-cause death or AHF hospitalization). Of 13,105 patients (10,600/2505 from the Spanish/Swiss cohorts, respectively), the median (interquartile range) age was 83 (74.87) years, and 51% were women. Of these, 484 (3.7%) received digoxin at discharge, which was associated with AF, female sex, left ventricular ejection fraction (LVEF) < 50%, and coming from the Spanish cohort. Parameters inversely associated with receiving digoxin at discharge included some chronic treatments, diabetes mellitus (DM), and chronic kidney disease (CKD). Digoxin initiation was not association with 90-day adverse events, adjusted hazard ratio (aHR) = 0.939 (0.769-1.146), but there was an interaction for CKD, aHR = 1.390 (0.831-2.325) vs. 0.854 (0.682-1.183), p = 0.039, and for cohort pertinence, with higher risk in the Swiss cohort; aHR = 1.405 (0.827-2.386) vs. 0.862 (0.689-1.077), p = 0.046. Digoxin initiation after an AHF episode was more frequent in the Spanish cohort and was associated with certain patient characteristics (AF, female sex, reduced LVEF, no DM, no CKD), but had no effect on 90-day outcomes.

Compromised chronic efficacy of a glucokinase activator AZD1656 in mouse models for common human GCKR variants

Glucokinase activators (GKAs) have been developed as blood glucose lowering drugs for type 2 diabetes. Despite good short-term efficacy, several GKAs showed a decline in efficacy chronically during clinical trials. The underlying mechanisms remain incompletely understood. We tested the hypothesis that deficiency in the liver glucokinase regulatory protein (GKRP) as occurs with common human GCKR variants affects chronic GKA efficacy. We used a Gckr-P446L mouse model for the GCKR exonic rs1260326 (P446L) variant and the Gckr-del/wt mouse to model transcriptional deficiency to test for chronic efficacy of the GKA, AZD1656 in GKRP-deficient states. In the Gckr-P446L mouse, the blood glucose lowering efficacy of AZD1656 (3 mg/kg body wt) after 2 weeks was independent of genotype. However after 19 weeks, efficacy was maintained in wild-type but declined in the LL genotype, in conjunction with raised hepatic glucokinase activity and without raised liver lipids. Sustained blood glucose lowering efficacy in wild-type mice was associated with qualitatively similar but more modest changes in the liver transcriptome compared with the P446L genotype, consistent with GKA therapy representing a more modest glucokinase excess than the P446L genotype. Chronic treatment with AZD1656 in the Gckr-del/wt mouse was associated with raised liver triglyceride and hepatocyte microvesicular steatosis. The results show that in mouse models of liver GKRP deficiency in conjunction with functional liver glucokinase excess as occurs in association with common human GCKR variants, GKRP-deficiency predisposes to declining efficacy of the GKA in lowering blood glucose and to GKA induced elevation in liver lipids.

A Pilot Interprofessional Education Curriculum for Optimizing Mental Health in Chronic Pain Treatment and Understanding Interprofessional Practice.

With the urgent need for clinicians capable of responding to the opioid crisis, an interprofessional education (IPE) pilot curriculum was launched to assess trainee self-efficacy in managing chronic pain and mental health conditions, and attitudes toward interprofessional practice among resident physicians, family nurse practitioners (FNP), and physician assistant (PA) students. This study involved the implementation of a pilot curriculum consisting of five interactive IPE sessions. All invited trainees across two academic institutions were asked to complete the assessments. Self-efficacy in managing chronic pain and mental health was measured at baseline and following IPE training using a researcher-developed tool, while attitudes toward interprofessional practice were measured with the Attitudes Toward Health Care Teams scale. Resident physicians were compared to FNP/PA students to examine differences between groups and within groups over time. The final analysis involved 25 trainees who attended at least one IPE training session and completed pre-session and post-session surveys. The total pre-session survey and post-session survey response rate was 37.5% (n=36). Self-efficacy in chronic pain management improved among the resident physician (mean=3.85 ±0.40) and FNP/PA groups (mean=3.84±0.46) (p=0.05 and p=0.001), respectively. Self-efficacy in mental health management was not significantly improved among resident physicians (mean=3.41±0.49, p=0.48), but improved among FNP/PA students (mean=3.46±0.31, p<0.001). There was no difference in attitudes toward interprofessional practice. While IPE training did not result in attitudinal changes toward interprofessional practice, it shows potential for improving self-efficacy in managing chronic pain and mental health, particularly among FNP/PA trainees. This study was limited by a small sample size of trainees included in the finalanalysis.

The mitigating effects and mechanisms of Bacillus cereus on chronic cadmium poisoning in Litopenaeus vannamei based on histopathological, transcriptomic, and metabolomic analyses

Shrimp are non-negligible victims of cadmium (Cd) contamination, and there is still a lack of strategies for mitigating Cd toxicity in shrimp. Bacillus cereus, with its significant heavy metal (HM) tolerance and chelating effects, is a representative beneficial bacterium to be investigated for mitigating the toxicity of Cd exposure. This study revealed the effects and potential mechanisms of B. cereus in mitigating chronic Cd toxicity in shrimp by analyzing growth performance, hepatopancreatic Cd accumulation, pathology, as well as comprehensive hepatopancreatic transcriptomics and metabolomics in Litopenaeus vannamei. The results showed that shrimp's growth inhibition, hepatopancreatic Cd accumulation and physiological structure damage in B. cereus+chronic Cd group were effectively alleviated compared with the chronic Cd treatment group. The pathways related to amino acid metabolism, glycolipid metabolism, immune response, and antioxidant stress were significantly activated in the B. cereus+chronic Cd group, including glycolysis, pentose phosphate pathway, oxidative phosphorylation, biosynthesis of amino acids, and biosynthesis of unsaturated fatty acids pathways. The key differentially expressed genes (e.g., macrophage migration inhibitory factor, glycine cleavage system H protein, glycine dehydrogenase, phosphoglucomutase-2, asparaginase, ATP synthase subunit, cytochrome c, and 4-hydroxyphenylpyruvate dioxygenase) and metabolites (e.g., L-leucine, D-ribose, gluconic acid, 6-Phosphogluconic acid, sedoheptulose 7-phosphate, 1-Kestose, glyceric acid, arachidic acid, prostaglandins, 12-Keto-tetrahydro-leukotriene B4, and gamma-glutamylcysteine) associated with the above pathways were significantly altered. This study demonstrated that B. cereus is an effective mitigator for the treatment of chronic Cd poisoning in shrimp. B. cereus may play a role in alleviating the toxicity of Cd by enhancing the antioxidant performance, immune defense ability, metabolic stability, and energy demand regulation of shrimp. The study provides reference materials for the study of B. cereus in alleviating Cd toxicity of shrimp and broadens the application of probiotics in treating HM toxicity.

Novel Treatments in Refractory Recurrent Pericarditis.

Refractory recurrent pericarditis is a troublesome condition that severely impairs the quality of life of affected patients and significantly increases healthcare spending. Until recently, therapeutic options included only a few medications and most of the patients resorted to chronic glucocorticoid treatment with steroid dependence. In the most recent decade, the introduction of interleukin-1 blockers in clinical practice has revolutionized the treatment of glucocorticoid-dependent and colchicine-resistant recurrent pericarditis due to their excellent efficacy and good safety profile. The rationale for the introduction of this class of medications in clinical practice is the autoinflammatory nature of recurrent pericarditis in a substantial rate of cases, with interleukin-1 being the main pro-inflammatory cytokine involved in this context. This review aims to discuss the contemporary available evidence from original research and real-world data on interleukin-1 blocker use in refractory recurrent pericarditis, in terms of indications, mechanism of action, efficacy, side effects, and recommended treatment protocols. Moreover, novel treatment proposals, such as hydroxychloroquine, beta blockers, and cannabidiol, which showed encouraging preliminary results, are addressed. Finally, gaps in knowledge, unmet needs, and future perspectives related to recurrent pericarditis are thoroughly discussed.

Resveratrol Mitigates Cognitive Impairments and Cholinergic Cell Loss in the Medial Septum in a Mouse Model of Gradual Cerebral Hypoperfusion.

Vascular cognitive impairment and dementia (VCID) is the second leading cause of dementia. There is currently no effective treatment for VCID. Resveratrol (RSV) is considered an antioxidant; however, our group has observed pleiotropic effects in stroke paradigms, suggesting more effects may contribute to mechanistic changes beyond antioxidative properties. The main goal of this study was to investigate if administering RSV twice a week could alleviate cognitive declines following the induction of a VCID model. Additionally, our aim was to further describe whether this treatment regimen could decrease cell death in brain areas vulnerable to changes in cerebral blood flow, such as the hippocampus and medial septum. We hypothesized RSV treatments in a mouse model of gradual cerebral hypoperfusion protect against cognitive impairment. We utilized gradual bilateral common carotid artery stenosis (GBCCAS) via the surgical implantation of ameroid constrictor devices. RSV treatment was administered on the day of implantation and twice a week thereafter. Cerebral perfusion was measured by laser speckle contrast imaging, and cognitive functions, including the recognition memory, the spatial working memory, and associative learning, were assessed by novel object recognition (NOR), Y-maze testing, and contextual fear conditioning (CFC), respectively. RSV treatment did not alleviate cerebral perfusion deficits but mitigated cognitive deficits in CFC and NOR after GBCCAS. Despite these deficits, no hippocampal pathology was observed; however, cholinergic cell loss in the medial septum was significantly increased after GBCCAS. This cholinergic cell loss was mitigated by RSV. This study describes a novel mechanism by which chronic RSV treatments protect against a VCID-induced cognitive decline through the preservation of cholinergic cell viability to improve memory performance.

RNA-binding protein GIGYF2 orchestrates hepatic insulin resistance through STAU1/PTEN-mediated disruption of the PI3K/AKT signaling cascade

BackgroundObesity is well-established as a significant contributor to the development of insulin resistance (IR) and diabetes, partially due to elevated plasma saturated free fatty acids like palmitic acid (PA). Grb10-interacting GYF Protein 2 (GIGYF2), an RNA-binding protein, is widely expressed in various tissues including the liver, and has been implicated in diabetes-induced cognitive impairment. Whereas, its role in obesity-related IR remains uninvestigated.MethodsIn this study, we employed palmitic acid (PA) exposure to establish an in vitro IR model in the human liver cancer cell line HepG2 with high-dose chronic PA treatment. The cells were stained with fluorescent dye 2-NBDG to evaluate cell glucose uptake. The mRNA expression levels of genes were determined by real-time qRT-PCR (RT-qPCR). Western blotting was employed to examine the protein expression levels. The RNA immunoprecipitation (RIP) was used to investigate the binding between protein and mRNA. Lentivirus-mediated gene knockdown and overexpression were employed for gene manipulation. In mice, an IR model induced by a high-fat diet (HFD) was established to validate the role and action mechanisms of GIGYF2 in the modulation of HFD-induced IR in vivo.ResultsIn hepatocytes, high levels of PA exposure strongly trigger the occurrence of hepatic IR evidenced by reduced glucose uptake and elevated extracellular glucose content, which is remarkably accompanied by up-regulation of GIGYF2. Silencing GIGYF2 ameliorated PA-induced IR and enhanced glucose uptake. Conversely, GIGYF2 overexpression promoted IR, PTEN upregulation, and AKT inactivation. Additionally, PA-induced hepatic IR caused a notable increase in STAU1, which was prevented by depleting GIGYF2. Notably, silencing STAU1 prevented GIGYF2-induced PTEN upregulation, PI3K/AKT pathway inactivation, and IR. STAU1 was found to stabilize PTEN mRNA by binding to its 3’UTR. In liver cells, tocopherol treatment inhibits GIGYF2 expression and mitigates PA-induced IR. In the in vivo mice model, GIGYF2 knockdown and tocopherol administration alleviate high-fat diet (HFD)-induced glucose intolerance and IR, along with the suppression of STAU1/PTEN and restoration of PI3K/AKT signaling.ConclusionsOur study discloses that GIGYF2 mediates obesity-related IR by disrupting the PI3K/AKT signaling axis through the up-regulation of STAU1/PTEN. Targeting GIGYF2 may offer a potential strategy for treating obesity-related metabolic diseases, including type 2 diabetes.Graphical

Translation and cultural adaption of the control preference scale across various care settings in a Danish hospital

BackgroundIn recent decades, there has been a growing emphasis on involving patients in healthcare decision-making, driven by political, ethical, and research considerations. Although patient involvement is associated with improved health outcomes, understanding patient preferences regarding their role in decision-making is crucial for effective interventions. The Control Preferences Scale (CPS) measures patient preferences along a continuum from passive to active participation. However, its application in Denmark necessitates translation and cultural adaptation.MethodologyThis study aimed to translate and culturally adapt the CPS for Danish use across diverse healthcare settings: acute care, cancer care, elective surgery, chronic medical treatment, and parental involvement in pediatric care. Following a cross-sectional design, the translation process was systematically planned and executed using Beaton’s guidelines, including the five stages: forward and back translation, synthesis, expert review, and pre-testing.ResultsThe translation and adaption process was carried out successfully. Few linguistic challenges were identified and resolved by the expert review. The findings of the pre-testing indicated high acceptability and usability of the adapted CPS among 152 Danish patients and parents. The collaborative role emerged as the most preferred across settings (69.8%), with passive roles more prevalent among cancer patients (30%) and parents waiting with their child to see a pediatrician (23.3%). Notable, more women preferred collaborative or active roles (83.9%) than men (73.9%). The content validity assessment yielded positive feedback, affirming the relevance and comprehensiveness of the CPS.ConclusionsIn summary, the adaptation and validation of the CPS for Danish use proved successful, providing a valuable tool for assessing patient’s role preferences in healthcare decision-making. However, future studies are recommended to ensure construct validity and reliability through psychometric testing.

Iron metabolism in sickle cell disease patients undergoing chronic red blood cell exchange: A delicate homeostasis in balance.

Sickle cell disease (SCD) is an inherited haemoglobinopathy associated with significant morbidity and mortality. Automated red blood cell exchange (aRCE) plays a key role in managing SCD, eliciting both therapeutic and prophylactic effects. The ideal post-apheresis Ht target for chronic aRCE treatment is not yet unanimously recognized, as well as iron homeostasis can be different among patients. Ross etal. reported their experience on the chronic management of SCD patients undergoing aRCE with a final post-exchange Ht higher than the value commonly adopted, analysing red blood cell transfusion requirements and iron-related outcomes in the study population. Commentary on: Ross etal. Automated red blood cell exchange with a post-procedure haematocrit targeted at 34% in the chronic management of sickle cell disease. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19674.

Effects of chronic naltrexone treatment on relapse-related behavior and neural responses to fentanyl in awake nonhuman primates.

Naltrexone, an opioid antagonist that blocks the reinforcing properties of opioid agonists, is often prescribed to preclude relapse to opioid use disorder (OUD) following detoxification. However, few laboratory studies have directly investigated the ability of naltrexone to alter relapse-inducing effects of opioid agonists, including their priming strength in reinstatement studies and their impact in brain regions known to be involved in drug-induced reinforcement in MRI studies. Here we directly address this issue by investigating the effects of continuous exposure to naltrexone on 1) fentanyl-induced reinstatement of drug-seeking behavior, 2) fentanyl-induced patterns of blood oxygenation level dependent (BOLD) activation in the nucleus accumbens (NAcc), and 3) fentanyl-induced changes in NAcc functional connectivity (FC) in awake non-human primates that are engaged in ongoing opioid self-administration studies. We found that naltrexone antagonizes the priming strength of fentanyl as shown by a rightward shift in its reinstatement dose-effect curve and that naltrexone surmountably antagonizes the BOLD response induced by fentanyl. However, while naltrexone also countered fentanyl's effects on NAcc FC, the effects were not surmounted by a higher dose of fentanyl. Together, these data suggest that, in contrast to naltrexone's modulation of fentanyl's effects on behavior and BOLD responses, their interactive effects on FC between multiple brain regions do not reflect their receptor-mediated activity. Additionally, we demonstrated opposing effects in the absence and presence of naltrexone on NAcc FC at baseline (i.e., in the absence of any fentanyl prime) suggesting that naltrexone alters FC at baseline, even though naltrexone appears behaviorally silent in the absence of an agonist prime. Together these data provide additional insight into ways in which naltrexone interacts with opioid agonists, both behaviorally and in the brain. Further understanding the effects of opioid agonists on patterns of FC could help elucidate our understanding of the neural processes that contribute to the initiation of and relapse to opioid-seeking behavior in OUD.

Insomnia among patients with chronic pain: A retrospective study.

Insomnia can coexist with chronic pain and is a major cause of rapidly increasing medical expenses. However, insomnia has not been fully evaluated in patients with chronic pain. This retrospective study aimed to identify the risk factors for insomnia in patients with chronic non-cancer pain. A total of 301 patients with chronic non-cancer pain were enrolled. Patients with the Athens insomnia scale scores ≥ 6 and < 6 were classified into insomnia (+) and insomnia (-) groups, respectively. All patients completed self-report questionnaires as part of their chronic pain treatment approach. Univariate and multivariate analyses were performed to predict insomnia. We found that 219 of 301 (72.8%) patients met the AIS criteria for insomnia. Significant differences were depicted between patients with and without insomnia in terms of body mass index, numeric rating scale, pain catastrophizing scale, hospital anxiety, and depression scale (HADS), pain disability assessment scale, EuroQol 5 dimension (EQ5D), and pain self-efficacy questionnaire. Multiple regression analysis identified the numeric rating scale, HADS, and EQ5D scores as factors related to insomnia in patients with chronic non-cancer pain. Anxiety, depression, and disability were associated with a greater tendency toward insomnia. HADS and EQ5D scores are useful screening tools for preventing insomnia in patients with chronic non-cancer pain.

Drug Consumption and Hydration Status: Analysis of the Associations in an Elder Population.

Hydration status plays a key role in healthy ageing, and it is potentially affected by several factors, including drug consumption. However, research on this issue to date is scarce, especially in highly vulnerable groups, such as the elderly. We aimed to study the relationship linking hydration status, analysed by means of a validated questionnaire, 24 h urine analysis, body composition assessment, and drug consumption in a sample of old adults. A total of 144 elders were included in the study. Cardiovascular drug consumption was significantly associated with a lower water intake in men (β = -0.282, p = 0.029). Moreover, urinary analysis revealed that total drug intake as well as the consumption of diuretics and cardiovascular drugs were associated with poorer hydration status, whereas genito-urinary drugs were associated with an opposite effect, and these results were confirmed in terms of body composition. Hence, total drug consumption (β = -0.205), diuretic (β = -0.408), cardiovascular (β = -0.297), and genito-urinary drugs (β = 0.298) were significantly associated (p < 0.05) with total body water. The obtained results confirmed the impact of chronic treatment with certain drugs on hydration status. Nutritional interventions may be of great interest in certain population groups in order to prevent complications due to altered hydration status.

Nanomedicine: An Emerging Tool in Healing Chronic Wounds and its Opportunities

Chronic wounds generally take a lot of time to recover, which becomes a cause of worry for the patient and also makes it difficult to manage them. Chronic wound affects the minds of millions of people worldwide, which results in a high mortality rate. Nanomedicine has emerged as a promising tool in addressing this issue of chronic wounds. Nanomedicine in chronic wound healing holds the potential to revolutionize wound care by offering various personalized treatments and improving patient outcomes. Advanced wound dressings and nanofibresscaffolds promote tissue regeneration, which also accelerates wound closure. Nanomedicine is also able to provoke the various cellular and molecular mechanisms that are involved in the wound microenvironment, showing the anti-inflammatory, antibacterial, and angiogenetic effects. The gene therapy and various inflammation modulations using this emerging tool of nanotechnology show promising results in managing the various chronic wounds. Nanomedicine offers innovative approaches to address these challenges. Nanomedicine also plays a crucial role in tissue engineering, which can also be used for chronic wound treatment. Nanotechnology has enabled the various development of advanced wound dressings and has improved various properties. Nanomedicine also uses antimicrobial nanomaterials, such as silver nanoparticles, to combat the various infections in chronic wounds. The main aim of the review is to provide a concise overview of nanomedicine as a recent tool in healing chronic wounds and also its various opportunities for curing chronic wounds.