Challenges Of Medical Care Research Articles

Проблемы организации помощи раненым и больным русским и сербским воинам на Салоникском фронте (1916–1917)

Both the Russian and Serbian armies faced challenges with arranging medical support for their soldiers on the Salonika front. Upon agreement with the allies, assistance to both Russian and Serbian wounded and sick soldiers was to be provided by the French government. This did not work for the Serbian Military Medical Department which had made significant efforts to establish its own infirmaries and hospitals on the Salonika Front since 1916. By the summer of 1916, they had three army hospitals, then four by the fall of the same year. The Russian headquarters followed suite, relying on the already existing Russian medical institutions (the Piraeus Hospital and the St. Demetrius of Thessaloniki Hospital in Thessaloniki). The necessary funds were allocated by the Russian Red Cross Society Administration. Helping the Russian headquarters to overcome challenges connected with medical care for Russian soldiers, Russian imperial diplomats also monitored the issues of helping the Serbs: a sanitary detachment of the Petrograd Slavic Charity was sent to the Salonika Front (senior medical officer Y. I. Chabrov). His fate fully reflected the changed balance of power in the Balkans. Neither the Serbian nor the French government arranged independent sanitary detachments reporting only to Petrograd. They wanted to have full control over the situation. The author concludes that the challenges of medical care for both Russian and Serbian wounded soldiers on the Salonika front were related to the weakening of Russia’s authority in the international arena and the depletion of its resources, including financial ones.

Fatigue in chronic physical diseases

The term fatigue is used to describe states of unusual tiredness and exhaustion that can occur in connection with various chronic diseases, particularly cancer, multiple sclerosis, Parkinson's disease and rheumatoid arthritis. In contrast to states of exhaustion in healthy people, fatigue is characterized by the fact that it can last for long periods, is disproportionate to previous activities and does not subside after recovery phases. Fatigue is described as amultidimensional problem that encompasses physical, emotional and cognitive aspects and is associated with ahigh level of subjective suffering. Depending on the severity and course of the symptoms, fatigue is associated with aseverely reduced quality of life and it impairs participation and coping with everyday life. It also makes professional reintegration and reemployment more difficult. Although we cannot yet fully explain the aetiology and pathogenesis, fatigue in physical illnesses must be understood based on amultifactorial biopsychosocial model. The possibilities of diagnostics and an overview of various measures for clarifying fatigue are presented. The challenges for medical care are also outlined and advice is given on how to deal with them in everyday clinical practice.

Stimuli-Responsive NO Delivery Platforms for Bacterial Infection Treatment.

The prevalence of drug-resistant bacterial infections has emerged as a grave threat to clinical treatment and global human health, presenting one of the foremost challenges in medical care. Thus, there is an urgent imperative to develop safe and efficacious novel antimicrobial strategies. Nitric oxide (NO) is a recognized endogenous signaling molecule, which plays a pivotal role in numerous pathological processes. Currently, NO has garnered significant interest as an antibacterial agent due to its capability to eradicate bacteria, disrupt biofilms, and facilitate wound healing, all while circumventing the emergence of drug resistance. However, the inherently unstable characteristic of NO therapeutic gas renders the controlled administration of NO gases exceedingly challenging. Hence, in this review, the current challenge of bacterial infection is discussed; then it is briefly elucidated the antibacterial mechanism of NO and comprehensively delineate the recent advancements in stimulus-responsive NO delivery platforms, along with their merits, obstacles, and prospective avenues for clinical application. This review offers guidance for future advancements in NO-medicated anti-infection therapy is hoped.

Living with Atypical Hemolytic Uremic Syndrome in the Netherlands: Patient and Family Perspective

IntroductionAtypical hemolytic uremic syndrome (aHUS) poses a significant health challenge due to its rarity and severity within the spectrum of thrombotic microangiopathy (TMA). Despite efforts to optimize and personalize health care for aHUS patients, understanding the individual experiences, needs and desires of aHUS patients and relatives remains limited. MethodsHere we present a nationwide, exploratory, qualitative interview study with a direct content analysis approach. In-depth interviews and a six-week evaluation were audio-recorded and conducted using a semi-structured topic guide, based on the Institute for Positive Health (IPH) model. ResultsAnalysis of ten interviews involving six aHUS patients and thirteen relatives revealed the prevalence of long-term disease symptoms in adult patients, notably fatigue, which significantly impacted daily functioning. Moreover, the resilience demonstrated by patients and their relatives was noteworthy, yet the acute phase of aHUS and the unpredictable nature of disease recurrence could profoundly affect mental well-being. The emotional toll of aHUS is pervasive, with feelings of fear, guilt and trauma persisting across disease phases in both patients and relatives. Challenges in medical care, including delays in diagnosis and the need for personalized and uniform protocols, were highlighted. Support was deemed crucial, indicating the necessity for enhancements in the accessibility of comprehensible disease information and psychological counselling. At last, complexities surrounding genetic testing and carriership were discussed. ConclusionThis study underscores the profound, enduring and multifaced impact of aHUS. The insights gleaned from the experiences and needs of aHUS patients and their relatives could lay the foundation for development and implementation of more personalized innovations in aHUS healthcare.

Evaluating the global prevalence of insomnia during pregnancy through standardized questionnaires and diagnostic criteria: a systematic review and meta-analysis.

Insomnia during pregnancy presents significant medical care challenges and heightens the risk of adverse outcomes for both pregnant women and fetuses. This study undertook a meta-analysis to assess the global prevalence of insomnia during pregnancy, examining both the overall prevalence and regional variations. The aim of this study was to perform a meta-analysis of articles indexed in PubMed, Embase, and Web of Science from the inception of these databases up to February 29, 2024. The study systematically reviewed the global prevalence of gestational insomnia and explored potential moderating factors, encompassing research type, publication date, regional influences, maternal age, pregnancy status, depressive symptoms, and anxiety symptoms. Forty-four studies, encompassing a total of 47,399,513 participants, were included in the analysis. The overall prevalence of insomnia symptoms during pregnancy was 43.9%. Regional factors and depression emerged as the main factors affecting insomnia, with Europe (53.6%) surpassing North America (41.0%), followed by South America (50.6%) and Asia (40.7%). High depression rates (56.2%) correlated with increased insomnia prevalence compared to low depression rates (39.8%). The type of research and publication date showed no significant impact on the prevalence of insomnia symptoms. The meta-analysis results indicated that the prevalence of insomnia symptoms was higher during pregnancy, especially among pregnant women who were in a highly depressed state or located in the European region. PROSPERO, identifier CRD42018104460.

Outcome of Chronic Foot Osteomyelitis Treated With Hyperbaric Oxygen: An Observational Study.

Chronic refractory osteomyelitis of the foot stands as a formidable challenge in medical care, associated with significant morbidity and escalating healthcare costs. Traditional therapeutic approaches, including surgical debridement and systemic antibiotics, often fall short, leaving patients and clinicians in search of more efficacious interventions. Hyperbaric oxygen therapy (HBOT), an innovative therapeutic modality, has recently emerged as a promising adjunct therapy, offering a beacon of hope in this therapeutic conundrum. In this groundbreaking observational study, we meticulously analyzed the experiences of 80 patients suffering from chronic refractory osteomyelitis of the foot. Following surgical debridement and tailored antibiotic therapy, each patient was treated with HBOT at 2.5 atmospheres absolute for 120 min, 5 days a week, spanning an average of 50 days. Our primary endpoints focused on complete eradication of infection, recurrence metrics, and any adverse effects linked to HBOT. Astonishingly, 68 of the 80 patients (85%) achieved a total infection clearance, maintaining this status through a mean follow-up period of 36 months, all without a single report of HBOT-induced complications. Our compelling findings advocate that HBOT, synergized with standard surgical and antibiotic regimens, can revolutionize the treatment landscape for chronic refractory osteomyelitis of the foot. Given these promising preliminary results, there's an imperative need for extensive research to delineate the long-term advantages and to fine-tune HBOT protocols, potentially paving the way for a new therapeutic gold standard.

Radiation therapy for cancer is potentially associated with reduced growth of concomitant abdominal aortic aneurysm

PurposeCo-prevalence of abdominal aortic aneurysm (AAA) and cancer poses a unique challenge in medical care since both diseases and their respective therapies might interact. Recently, reduced AAA growth rates were observed in cancer patients that received radiation therapy (RT). The purpose of this study was to perform a fine-grained analysis of the effects of RT on AAA growth with respect to direct (infield) and out-of-field (outfield) radiation exposure, and radiation dose-dependency.MethodsA retrospective single-center analysis identified patients with AAA, cancer, and RT. Clinical data, radiation plans, and aneurysm diameters were analyzed. The total dose of radiation to each aneurysm was computed. AAA growth under infield and outfield exposure was compared to patients with AAA and cancer that did not receive RT (no-RT control) and to an external noncancer AAA reference cohort.ResultsBetween 2003 and 2020, a total of 38 AAA patients who had received well-documented RT for their malignancy were identified. AAA growth was considerably reduced for infield patients (n = 18) compared to outfield patients (n = 20), albeit not significantly (0.8 ± 1.0 vs. 1.3 ± 1.6 mm/year, p = 0.28). Overall, annual AAA growth in RT patients was lower compared to no-RT control patients (1.1 ± 1.5 vs. 1.8 ± 2.2 mm/year, p = 0.06) and significantly reduced compared to the reference cohort (1.1 ± 1.5 vs. 2.7 ± 2.1 mm/year, p < 0.001). The pattern of AAA growth reduction due to RT was corroborated in linear regression analyses correcting for initial AAA diameter. A further investigation with respect to dose-dependency of radiation effects on AAA growth, however, revealed no apparent association.ConclusionIn this study, both infield and outfield radiation exposure were associated with reduced AAA growth. This finding warrants further investigation, both in a larger scale clinical cohort and on a molecular level.

Prognostic scale for in-hospital mortality in patients with COVID-19 viral pneumonia

The COVID-19 pandemic represented a challenge in medical care. A tool would be very useful to establish the prognosis of in-hospital death that is reliable and can be applied to the Mexican population entitled to the IMSS. To propose a prognostic scale to stratify patients with viral pneumonia COVID-19 in the emergency services. A nested case-control study was conducted in a cohort of patients who were consecutively admitted to the emergency department with viral pneumonia COVID-19. The cases were those patients who died, and the controls were those who were discharged due to health improvement. An association analysis was performed between the variables with significant differences between groups. Subsequently, the association was adjusted using a multivariate logistic regression model, from which the prognostic scale was developed. A total of 70 subjects with COVID-19 were included, 34 cases and 36 controls. Chronic diseases, smoking, severe pulmonary involvement diagnosed by tomography, leukocytosis, and pulse oximetry less than 80% with were associated with in-hospital mortality; Odds Ratio (OR) of >1.1. Vaccination was a protective factor (OR = 0.04, CI95%: 0.01-0.16). A score greater than 3 points on the prognostic scale predicts in-hospital mortality with a specificity of 0.86 and a sensitivity of 0.73. The proposed prognostic scale can be a useful tool in the classification of patients with COVID-19 viral pneumonia in the emergency room services of secondary care level Hospitals.

“Adults with congenital heart defects”: current challenges in medical care. Part II: infective endocarditis, pulmonary hypertension, aortopathy, cardiac surgical aspects, psychocardiology, unresolved problems and future aspects

“Adults with congenital heart defects”: current challenges in medical care. Part II: infective endocarditis, pulmonary hypertension, aortopathy, cardiac surgical aspects, psychocardiology, unresolved problems and future aspects

“Adults with congenital heart defects”: current challenges in medical care. Part I: the problem, structure of care, heart failure, cardiac arrhythmias

“Adults with congenital heart defects”: current challenges in medical care. Part I: the problem, structure of care, heart failure, cardiac arrhythmias

OP05 High-dimensional single-cell analysis identifies cellular signatures associated with response to vedolizumab therapy in ulcerative colitis

Abstract Background The unpredictability of response to biological therapy in ulcerative colitis (UC) patients, including vedolizumab (VDZ), an anti-α4β7 integrin antibody, poses a serious challenge for medical care. This study aims to identify the relevant cellular and molecular signatures that mark response to VDZ by combining single-cell transcriptomics (scRNAseq) and high-dimensional flow cytometry (Cytek). Methods Gut biopsies and peripheral blood mononuclear cells (PBMCs) from patients with active UC were collected 2 weeks prior and 14 weeks after starting VDZ therapy. Response was evaluated at week 14 based on endoscopy and Physician Global Assessment. Transcriptome profiles of 159.188 and 95.057 high-quality single cells were generated from biopsies and PBMCs, respectively. Additional 797.670 CD45+ mucosal cells and 900.000 PBMCs were processed for validating scRNAseq results by Cytek. Results From a total of 25 UC patients (mean age 41±12.7 years, 52% female, 36% anti-TNFα naive), 15 patients (60%) reached response at week 14. Patients with no prior use of anti-TNFα were more likely to achieve remission with VDZ compared to anti-TNFα exposed patients (89% vs 44% response rate, respectively). Analysis of cell abundances revealed a partial recovery of the epithelial and stromal cell mucosal compartments in responders at week 14. Both scRNAseq and Cytek show that in responders VDZ prevented T cells (CD8+IL17+ and CD4+PD1+ subsets) and innate immune cells (NKs, DCs and inflammatory monocytes) from entering mucosa, resulting in their enrichment in PBMCs. In contrast, non-response to VDZ was marked by an expansion of inflammatory fibroblasts and activated endothelial cells, and depletion of most epithelial subsets. VDZ retained CD4 T cells in PBMCs in non-responders, but failed to halt active mucosal inflammation at week 14. Strikingly, involvement of the innate immune cells in UC inflammation prior to VDZ treatment was much more prominent in non-responders who showed higher baseline abundance of NKs, ILCs, γδ-T cells, DCs and inflammatory monocytes in their peripheral blood and mucosa compared to responders. While VDZ inhibited integrin β7 expression on circulating T cells in all patients, only in responders it coincided with the lower mucosal abundance of lymphocytes, suggesting that T cells in non-responders might employ alternative, β7-independent trafficking routes. Conclusion This is the largest prospective scRNAseq study addressing the response to biological therapy in UC. We showed that active, innate immune cell-mediated inflammation marks the primary non-response to VDZ that persists prior to and throughout the treatment, accompanied by β7-independent lymphocyte migration.

3D Biofilm Models Containing Multiple Species for Antimicrobial Testing of Wound Dressings.

The treatment of chronic wounds presents a major challenge in medical care. In particular, the effective treatment of bacterial infections that occur in the form of biofilms is of crucial importance. To develop successful antibiofilm strategies for chronic wound treatment, biofilm models are needed that resemble the in vivo situation, are easy to handle, standardizable, and where results are readily transferable to the clinical situation. We established two 3D biofilm models to distinguish the effectiveness of wound dressings on important microorganisms present in chronic wounds. The first 3D biofilm model contains Staphylococcus aureus, Escherichia coli, and Acinetobacter baumannii, while the second is based on Pseudomonas aeruginosa. Bacteria are cultivated in a nutrient-rich agar/gelatin mix, into which air bubbles are incorporated. This results in a mature biofilm growing in clusters similar to its organization in chronic wounds. The models are convenient to use, have low variability and are easy to establish in the laboratory. Treatment with polihexanide and silver-containing wound dressings showed that the models are very well suited for antimicrobial testing and that they can detect differences in the efficacy of antimicrobial substances. Therefore, these models present valuable tools in the development of effective antibiofilm strategies in chronic wounds.

Pulsed low-intensity laser treatment stimulates wound healing without enhancing biofilm development in vitro.

Treating infected or chronic wounds burdened with biofilms still is a major challenge in medical care. Healing-stimulating factors lose their efficacy due to bacterial degradation, and antimicrobial substances negatively affect dermal cells. Therefore, alternative treatment approaches like the pulsed low intensity laser therapy (LILT) require consideration. The effect of pulsed LILT (904nm, in three frequencies) on relevant human cells of the wound healing process (fibroblasts (BJ), keratinocytes (HaCaT), endothelial cells (HMEC), monocytes (THP-1)) were investigated in in-vitro and ex-vivo wound models with respect to viability, proliferation and migration. Antimicrobial efficacy of the most efficient frequency in cell biological analyses of LILT (3200Hz) was determined in a human biofilm model (lhBIOM). Quantification of bacterial load was evaluated by suspension method and qualitative visualization was performed by scanning electron microscopy (SEM). Pulsed LILT at 904nm at 3200Hz±50% showed the most positive effects on metabolic activity and proliferation of human wound cells in vitro (after 72h - BJ: BPT 0.97±0.05 vs. 0.75±0.04 (p=0.0283); HaCaT: BPT 0.79±0.04 vs. 0.59±0.02 (p=0.0106); HMEC: 0.74±0.02 vs. 0.52±0.04 (p=0.009); THP-1: 0.58±0.01 vs. 0.64±0.01 (p>0.05) and ex vivo. Interestingly, re-epithelialization was stimulated in a frequency-independent manner. The inhibition of metabolic activity after TNF-α application was abolished after laser treatment. No impact of LILT on monocytes was detected. Likewise, the tested LILT regimens showed no growth rate reducing effects on three bacterial strains (after 72h - PA: -1.03%; SA: -0.02%; EF: -1,89%) and one fungal (-2.06%) biofilm producing species compared to the respective untreated control. Accordingly, no significant morphological changes of the biofilms were observed after LILT treatment in the SEM. Frequent application of LILT (904nm, 3200Hz) seems to be beneficial for the metabolism of human dermal cells during wound healing. Considering this, the lack of disturbance of the behavior of the immune cells and no growth-inducing effect on bacteria and fungi in the biofilm can be assigned as rather positive. Based on this combined mode of action, LILT may be an option for hard to heal wounds infected with persistent biofilms.

Design, Synthesis, and In Vitro, In Silico and In Cellulo Evaluation of New Pyrimidine and Pyridine Amide and Carbamate Derivatives as Multi-Functional Cholinesterase Inhibitors

Alzheimer disease is an age-linked neurodegenerative disorder representing one of the greatest medical care challenges of our century. Several drugs are useful in ameliorating the symptoms, even if none could stop or reverse disease progression. The standard approach is represented by the cholinesterase inhibitors (ChEIs) that restore the levels of acetylcholine (ACh) by inhibiting the acetylcholinesterase (AChE). Still, their limited efficacy has prompted researchers to develop new ChEIs that could also reduce the oxidative stress by exhibiting antioxidant properties and by chelating the main metals involved in the disease. Recently, we developed some derivatives constituted by a 2-amino-pyrimidine or a 2-amino-pyridine moiety connected to various aromatic groups by a flexible amino-alkyl linker as new dual inhibitors of AChE and butyrylcholinesterase (BChE). Following our previous studies, in this work we explored the role of the flexible linker by replacing the amino group with an amide or a carbamic group. The most potent compounds showed higher selectivity against BChE in respect to AChE, proving also to possess a weak anti-aggregating activity toward Aβ42 and tau and to be able to chelate Cu2+ and Fe3+ ions. Molecular docking and molecular dynamic studies proposed possible binding modes with the enzymes. It is noteworthy that these compounds were predicted as BBB-permeable and showed low cytotoxicity on the human brain cell line.

Review of time in therapeutic range of warfarin in a tertiary centre in Malaysia

Anticoagulation management is a recognized challenge in medical care. Complications of supratherapeutic anticoagulation are hemorrhagic stroke, major bleeding, and death. There is an even greater risk of ischemic stroke in AF, worsening of VTE associated with subtherapeutic dosing.

Challenges of medical care in urban areas - a conceptual framework for primary care in the city

Germany already has a high degree of urbanisation, and the share of urban population is expected to increase further. Thus, it is important to explore urban primary care from a scientific point of view. In this article, the author suggests a framework for urban primary care. Three core characteristics of urban areas are a high population density, a high population heterogeneity (including socioeconomic heterogeneity) and a fragmentation of health care and social care. These characteristics influence the health of urban dwelling population. Thus, these characteristics form the future challenges for urban primary care.

Toward the development of a vibrant, super-aged society: The future of medicine and society in Japan.

Toward the development of a vibrant, super-aged society: The future of medicine and society in Japan.

Functional Nanocarriers for Delivering Itraconazole Against Fungal Intracellular Infections.

Infectious diseases caused by intracellular microorganisms represent a significant challenge in medical care due to interactions among drugs during coinfections and the development of resistance in microorganisms, limiting existing therapies. This work reports on itraconazole (ITZ) encapsulated into functional polymeric nanoparticles for their targeted and controlled release into macrophages to fight intracellular infections. NPs are based on poly (lactic acid-co-glycolic acid) (PLGA) polymers of different compositions, molecular weights, and lactic acid–to–glycolic acid ratios. They were self-assembled using the high-energy nanoemulsion method and characterized by transmission electron microscopy, Fourier transform infrared spectroscopy (FT-IR), and differential scanning calorimetry. It was studied how the polymer-to-drug ratio, changes in the aqueous phase pH, and type and concentration of surfactant affected nanocarriers’ formation, drug-loading capacity, and encapsulation efficiency. Results showed that drug-loading capacity and encapsulation efficiency reached 6.7 and 80%, respectively, by lowering the pH to 5.0 and using a mixture of surfactants. Optimized formulation showed an initial immediate ITZ release, followed by a prolonged release phase that fitted better with a Fickian diffusion kinetic model and high stability at 4 and 37°C. NPs functionalized by using the adsorption and carbodiimide methods had different efficiencies, the carbodiimide approach being more efficient, stable, and reproducible. Furthermore, linking F4/80 and mannose to the NPs was demonstrated to increase J774A.1 macrophages’ uptake. Overall, in vitro assays showed the nanosystem’s efficacy to eliminate the Histoplasma capsulatum fungus and pave the way to design highly efficient nanocarriers for drug delivery against intracellular infections.

In vitro Activity of Antimicrobial Wound Dressings on P. aeruginosa Wound Biofilm.

The treatment of acute and chronic infected wounds with residing biofilm still poses a major challenge in medical care. Interactions of antimicrobial dressings with bacterial load, biofilm matrix and the overall protein-rich wound microenvironment remain insufficiently studied. This analysis aimed to extend the investigation on the efficacy of a variety of antimicrobial dressings using an in vitro biofilm model (lhBIOM) mimicking the specific biofilm-environment in human wounds. Four wound dressings containing polyhexanide (PHMB), octendine di-hydrochloride (OCT), cadexomer-iodine (C-IOD) or ionic silver (AG) were compared regarding their antimicrobial efficacy. Quantitative analysis was performed using a quantitative suspension method, separately assessing remaining microbial counts within the solid biofilm as well as the dressing eluate (representing the absorbed wound exudate). Dressing performance was tested against P. aeruginosa biofilms over the course of 6 days. Scanning electron microscopy (SEM) was used to obtain qualitative visualization on changes in biofilm structure. C-IOD demonstrated superior bacterial reduction. In comparison it was the only dressing achieving a significant reduction of more than 7 log10 steps within 3 days. Neither the OCT- nor the AG-containing dressing exerted a distinct and sustained antimicrobial effect. PHMB achieved a non-significant microbicidal effect (1.71 ± 0.31 log10 steps) at day 1. Over the remaining course (6 days) it demonstrated a significant microbistatic effect compared to OCT, AG and the control. Quantitative results in the dressing eluate correlate with those of the solid biofilm model. Overall, AG- and OCT-containing dressings did not achieve the expected anti-biofilm efficacy, while C-IOD performed best. Chemical interaction with the biofilms extrapolymeric substance (EPS), visualized in the SEM, and dressing configuration (agent concentration and release pattern) are suspected to be responsible. The unexpected low and diverse results of the tested antimicrobial dressings indicate a necessity to rethink non-debridement anti-biofilm therapy. Focussing on the combination of biofilm-disruptive (for EPS structure) and antimicrobial (for residing microorganisms) features, as with C-IOD, using dehydration and iodine, appears reasonably complementary and an optimal solution, as suggested by the here presented in vitro data.

Acute pain management among patients with opioid maintenance therapy: specificities and difficulties identified in primary care: a qualitative study

ObjectivesIn the last 30 years, opioid maintenance treatment prescription (OMT) has changed patients’ and also changed physicians’ practices. General practitioners (GPs) have to deal with patients on OMT who are...