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1.
Curr Drug Targets ; 25(4): 241-260, 2024.
Article in English | MEDLINE | ID: mdl-38288834

ABSTRACT

Cancer is the most widely studied disorder in humans, but proper treatment has not yet been developed for it. Conventional therapies, like chemotherapy, radiation therapy, and surgery, have been employed. Such therapies target not only cancerous cells but also harm normal cells. Conventional therapy does not result in specific targeting and hence leads to severe side effects. The main objective of this study is to explore the QDs. QDs are used as nanocarriers for diagnosis and treatment at the same time. They are based on the principle of theranostic approach. QDs can be conjugated with antibodies via various methods that result in targeted therapy. This results in their dual function as a diagnostic and therapeutic tool. Nanotechnology involving such nanocarriers can increase the specificity and reduce the side effects, leaving the normal cells unaffected. This review pays attention to different methods for synthesising QDs. QDs can be obtained using either organic method and synthetic methods. It was found that QDs synthesised naturally are more feasible than the synthetic process. Top or bottom-up approaches have also emerged for the synthesis of QDs. QDs can be conjugated with an antibody via non-covalent and covalent binding. Covalent binding is much more feasible than any other method. Zero-length coupling plays an important role as EDC (1-Ethyl-3-Ethyl dimethylaminopropyl)carbodiimide is a strong crosslinker and is widely used for conjugating molecules. Antibodies work as surface ligands that lead to antigen- antibody interaction, resulting in site-specific targeting and leaving behind the normal cells unaffected. Cellular uptake of the molecule is done by either passive targeting or active targeting. QDs are tiny nanocrystals that are inorganic in nature and vary in size and range. Based on different sizes, they emit light of specific wavelengths. They have their own luminescent and optical properties that lead to the monitoring, imaging, and transport of the therapeutic moiety to a variety of targets in the body. The surface of the QDs is modified to boost their functioning. They act as a tool for diagnosis, imaging, and delivery of therapeutic moieties. For improved therapeutic effects, nanotechnology leads the cellular uptake of nanoparticles via passive targeting or active targeting. It is a crucial platform that not only leads to imaging and diagnosis but also helps to deliver therapeutic moieties to specific sites. Therefore, this review concludes that there are numerous drawbacks to the current cancer treatment options, which ultimately result in treatment failure. Therefore, nanotechnology that involves such a nanocarrier will serve as a tool for overcoming all limitations of the traditional therapeutic approach. This approach helps in reducing the dose of anticancer agents for effective treatment and hence improving the therapeutic index. QDs can not only diagnose a disease but also deliver drugs to the cancerous site.


Subject(s)
Neoplasms , Quantum Dots , Theranostic Nanomedicine , Quantum Dots/chemistry , Humans , Neoplasms/diagnostic imaging , Neoplasms/therapy , Theranostic Nanomedicine/methods , Animals
2.
Can J Nurs Res ; 56(1): 69-80, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38092681

ABSTRACT

The onset of the COVID-19 pandemic led mental health professionals to change the way they engaged with clients, often replacing in-person consultations with virtual ones via telephone or videoconferencing. While studies have investigated the delivery of virtual physical health care, only a handful have investigated the delivery of virtual mental health. These specifically focussed on the outcomes of virtual care whether experiential, practical, or empirical. The transition from in-person to virtual care delivery due to the COVID-19 pandemic has been unexplored. Accordingly, the purpose of the study was to: (1) Explore the experiences of clients who had to transition from an in-person to a virtual provision of mental health care due to the COVID-19 pandemic, and; (2) Explore the nurses' experiences of this technological transition. Using an interpretive phenomenology methodology, semi-structured interviews were conducted with nurses and clients who have experienced the in-person to virtual transition of service delivery at a tertiary mental health hospital in Ontario, Canada. In this article, we focus on the results stemming from our interviews with clients. The themes generated from the analysis of client experiences are 1) the psychosocial impact of the COVID-19 pandemic on clients, (2) mixed feelings of clients towards nursing care delivered via technological means and (3) the role of nurses regarding transitioning of in-person care to technology-mediated care. These findings are relevant as mental health care hospitals are considering how they will deliver services once concerns with the transmission of the COVID-19 virus are resolved.


Subject(s)
COVID-19 , Mental Health Teletherapy , Psychiatric Nursing , Humans , COVID-19/epidemiology , Delivery of Health Care , Ontario , Pandemics
3.
Clin Lung Cancer ; 25(1): 1-8, 2024 01.
Article in English | MEDLINE | ID: mdl-37940410

ABSTRACT

Lung cancer is the leading cause of cancer death for women in multiple countries including the United States. Women are exposed to unique risk factors that remain largely understudied such as indoor pollution, second-hand tobacco exposure, biological differences, gender differences in tolerability and response to therapy in lung cancer, and societal gender roles, that create distinct survivorship needs. Women continue to lack representation in lung cancer clinical trials and are typically treated with data generated from majority male patient study populations, which may be inappropriate to extrapolate and generalize to females. Current lung cancer treatment and screening guidelines do not incorporate sex-specific differences and physicians also often do not account for gender differences when choosing treatments or discussing survivorship needs. To best provide targeted treatment approaches, greater representation of women in lung cancer clinical trials and further research is necessary. Clinicians should understand the unique factors and consequences associated with lung cancer in women; thus, a holistic approach that acknowledges environmental and societal factors is necessary.


Subject(s)
Lung Neoplasms , Humans , Male , Female , United States/epidemiology , Lung Neoplasms/epidemiology , Lung Neoplasms/therapy , Lung Neoplasms/etiology , Risk Factors , Sex Factors , Forecasting
4.
J Thorac Dis ; 15(10): 5773-5783, 2023 Oct 31.
Article in English | MEDLINE | ID: mdl-37969285

ABSTRACT

Background and Objective: Cystic fibrosis (CF) is a disorder that affects the cystic fibrosis transmembrane conductance regulator (CFTR). Without properly functioning CFTR channels, chloride does not exit respiratory epithelial cells, and consequently the mucus lining the surface of the cells becomes thick. This viscous mucus accumulates and causes abnormal function of the mucociliary apparatus, which can lead to bacterial colonization, infections with Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa), and eventually lung damage. Recent studies have shown that the increased susceptibility to respiratory infections in CF patients may also be due to defects in neutrophil function, but the exact mechanism is uncertain. Methods: The PubMed database was searched on February 10, 2023 and again on July 23, 2023 to compile a comprehensive list of clinical and experimental studies to evaluate neutrophil function in CF. The first search included a combination of MeSH terms: "cystic fibrosis" and "neutrophils/physiology". A separate second search included a combination of the MeSH terms: "neutrophils" and "cystic fibrosis transmembrane conductance regulator". Key Content and Findings: Neutrophils from patients with CF have decreased transfer of chloride into phagolysosomes after bacterial ingestion and have dysregulated degranulation. This reduces the production of toxic oxidative radicals, especially hypochlorous acid (HOCl), and reduces bactericidal activity. CFTR potentiators correct the dysregulated degranulation in patients with CF and increased neutrophil killing activity. A reduced concentration of chloride in in vitro assays also reduces neutrophil killing activity; these observations are relevant to the reduced chloride concentrations in respiratory secretions in patients with CF. Conclusions: This literature review summarizes studies that demonstrate that an important defect in CF neutrophils lies in the oxygen-dependent pathway in phagolysosomes and studies with ivacaftor demonstrate that this drug corrects CF neutrophil function. These studies demonstrate the potential utility of using easily available neutrophils to study drug effects in CF patients.

5.
Bioinformation ; 19(10): 1011-1014, 2023.
Article in English | MEDLINE | ID: mdl-37969666

ABSTRACT

Basic life support (BLS) provided right away can lower fatality rates. Cardiac arrest typically results in death within minutes if it is untreated. Therefore, it is of interest to assess how BLS training affected villagers. The pre-experimental one-group pre-test post-test design was chosen for the investigation. A non-probability volunteer sampling technique was adopted to collect a sample of 220 village residents who met the inclusion requirements. The participants received training in basic life support that is achieved by using a real-life role model, hands-on CPR instruction. Checklist served as a standardized method for assessing the BLS training program. The pre-test and post-test's means were 23.05 and 56.51, respectively, and their respective standard deviations were 11.89 and 8.27. The 'z test' calculation result is 12.36) The results showed that BLS training was more successful for villagers and that they required regular BLS training programs to maintain their BLS skill level.

6.
Pharm Nanotechnol ; 2023 Sep 12.
Article in English | MEDLINE | ID: mdl-37702235

ABSTRACT

BACKGROUND: The common symptom of systemic atherosclerosis is peripheral arterial disease(PAD), which occurs when the artery lumen in the lower extremities gradually becomes blocked by atherosclerotic plaque. The most frequent symptom of lower extremity PAD, called "vascular claudication," which is pain experienced when walking. Partial or total blockage of the peripheral arteries in the upper and lower limbs is called PAD. The danger of death from concurrent coronary artery and cerebrovascular atherosclerosis outweighs the risk of amputation. OBJECTIVE: However, niosomes have issues with fusion, aggregation, leakage, vesicle sedimentation, and difficulty in sterilizing. A more recent strategy known as pro-vesicular carriers was used to solve these issues. The formulations in Proniosomes are dry and anhydrous, protected with a non-ionic surfactant that serves as a carrier when combined with water. METHODS: Formulation prepared by organic solvent, surfactant, cholesterol, other components and hydration medium. Coacervation Phase separation Technique used for proniosome Nanoparticle. Box Bhenken Design is used for optimization batches. RESULTS: In this context, we shall discuss the development of Proniosome for the treatment of peripheral arterial diseases. From here, we know that proniosome nanoparticles is pro vesicular system good characteristics and effectiveness for treating peripheral arterial diseases. CONCLUSION: Proniosomes may be created using various techniques, which may impact how they develop along with the drug's characteristics. They increase the drug's stability while being delivered while being entrapped. They don't need particular conditions for handling, protection, storage, or industrial manufacturing.

7.
Eur J Health Econ ; 2023 Sep 20.
Article in English | MEDLINE | ID: mdl-37726429

ABSTRACT

BACKGROUND: This study aimed to conduct a systematic review of the cost-effectiveness studies of interventions to increase cervical cancer screening uptake rates in underserved women in Europe. METHODS: A search of Embase, Medline, Global Health, PsychINFO, and NHS Economic Evaluation Database was conducted for studies published between January 2000 and September 2022. Studies were eligible if they analysed the cost-effectiveness of any interventions to improve participation in cervical cancer screening among underserved women of any age eligible to participate in cervical cancer screening in European countries, in any language. Study characteristics and cost-effectiveness results were summarised. Study quality was assessed using the Drummond Checklist, and methodological choices were further compared. RESULTS: The searches yielded 962 unique studies, with 17 of these (from twelve European countries) meeting the eligibility criteria for data extraction. All studies focused on underscreened women as an overarching group, with no identified studies focusing on specific subgroups of underserved women. Generally, self-HPV testing and reminder interventions were shown to be cost-effective to increase the uptake rates. There was also research showing that addressing access issues and adopting different screening modalities could be economically attractive in some settings, but the current evidence is insufficient due to the limited number of studies. CONCLUSION: This systematic review has revealed a gap in the literature on the cost-effectiveness of interventions to improve uptake rates of cervical cancer screening through tailored provision for specific groups of underserved women.

8.
Cancers (Basel) ; 15(16)2023 Aug 08.
Article in English | MEDLINE | ID: mdl-37627044

ABSTRACT

Small cell lung cancer is an aggressive subtype of lung cancer with limited treatment options. Precision medicine has revolutionized cancer treatment for many tumor types but progress in SCLC has been slower due to the lack of targetable biomarkers. This review article provides an overview of emerging strategies for precision therapy in SCLC. Targeted therapies include targeted kinase inhibitors, monoclonal antibodies, angiogenesis inhibitors, antibody-drug conjugates, PARP inhibitors, and epigenetic modulators. Angiogenesis inhibitors and DNA-damaging agents, such as PARP and ATR inhibitors, have been explored in SCLC with limited success to date although trials are ongoing. The potential of targeting DLL3, a NOTCH ligand, through antibody-drug conjugates, bispecific T-cell engagers, and CAR T-cell therapy, has opened up new therapeutic options moving forward. Additionally, new research in epigenetic therapeutics in reversing transcriptional repression, modulating anti-tumor immunity, and utilizing antibody-drug conjugates to target cell surface-specific targets in SCLC are also being investigated. While progress in precision therapy for SCLC has been challenging, recent advancements provide optimism for improved treatment outcomes. However, several challenges remain and will need to be addressed, including drug resistance and tumor heterogeneity. Further research and biomarker-selected clinical trials are necessary to develop effective precision therapies for SCLC patients.

9.
Sleep Med ; 110: 60-67, 2023 10.
Article in English | MEDLINE | ID: mdl-37541132

ABSTRACT

Circadian dysrhythmias occur commonly in critically ill patients reflecting variable effects of underlying illness, ICU environment, and treatments. We retrospectively analyzed the relationship between clinical outcomes and 24-h urinary 6-sulfatoxymelatonin (aMT6s) excretion profiles in 37 critically ill patients with shock and/or respiratory failure. Nonlinear regression was used to fit a 24-h cosine curve to each patient's aMT6s profile, with rhythmicity determined by the zero-amplitude test. From these curves we determined acrophase, amplitude, phase, and night/day ratio. After assessing unadjusted relationships, we identified the optimal multivariate models for hospital survival and for discharge to home (vs. death or transfer to another facility). Normalized aMT6s rhythm amplitude was greater (p = 0.005) in patients discharged home than in those who were not, while both groups exhibited a phase delay. Patients with rhythmic aMT6s excretion were more likely to survive (OR 5.25) and be discharged home (OR 8.89; p < 0.05 for both) than patients with arrhythmic profiles, associations that persisted in multivariate modelling. In critically ill patients with shock and/or respiratory failure, arrhythmic and/or low amplitude 24-h aMT6s rhythms were associated with worse clinical outcomes, suggesting a role for the melatonin-based rhythm as a novel biomarker of critical illness severity.


Subject(s)
Melatonin , Humans , Critical Illness , Retrospective Studies , Circadian Rhythm , Biomarkers
10.
Curr Drug Targets ; 24(12): 934-944, 2023.
Article in English | MEDLINE | ID: mdl-37592775

ABSTRACT

BACKGROUND: Cancer is a life-threatening disease worldwide, but proper treatment has not yet been developed. Many therapies are available to treat cancer disorders, like chemotherapy, surgery, hormone therapy, and immunotherapy. Chemotherapy often relies on a combination of harmful, highly toxic platinum-based compounds. Also, there are chances of poor distribution of chemotherapeutic agents and cytotoxic to most cells which leads to damage to other healthy cells, also, there are chances of resistance. OBJECTIVE: The main objective of this study is the development of mesoporous silica nanoparticles. Mesoporous silica nanoparticles are recognized as carriers with high drug loading capacity and significant functionalized surface area for targeted drug delivery. Mesoporous silica nanoparticles have shape, particle size, pore volume, higher surface area, and the possibility of surface modification. Hence results in thermally and chemically stable nanomaterials. For targeted drug delivery, MSN is conjugated with a variety of ligands, including monoclonal antibodies, hyaluronic acid, transferrin, folic acid, etc., that have a particular affinity for the receptors that are overexpressed on the surface of malignant cells, so using this nanocarrier reducing the dose related toxicity of normal cell. METHODS: This review focuses on different methods for synthesizing mesoporous silica nanoparticles. Sol-gel method and modified stobber method were used for the synthesis of this nanoparticle. RESULTS: Successfully synthesized mesoporous silica nanoparticle with particle size around 50-200 nm and drug loading efficiency was found to be around 71%. CONCLUSION: Mesoporous silica nanoparticles are great carriers for intracellular and targeted drug delivery systems.

12.
Article in English | MEDLINE | ID: mdl-37395874

ABSTRACT

The rising global cancer rate is driving up the consumption of anticancer drugs. This causing a noticeable increase in the levels of these drugs in wastewater. The drugs are not metabolized effectively by the human body, leading to their presence in human waste, as well as in the effluent from hospitals and drug manufacturing industries. Methotrexate is a commonly used drug for treating various types of cancer. Its complex organic structure makes it difficult to degrade using conventional methods. The present work proposed a non-thermal pencil plasma jet treatment for methotrexate degradation. The air plasma produced in this jet setup is electrical characterized and plasma species/radicals are identified using emission spectroscopy. The degradation of drug is monitored by studying the change in solution physiochemical properties, HPLC-UV analysis, and removal of total organic carbon, etc.Results show that a 9-min plasma treatment completely degraded the drug solution that followed first-order degradation kinetics with rate constant 0.38 min-1 and 84.54% mineralization was observed. Additionally, an increase in electrical conductivity and dissolved solids compared to virgin water-plasma interaction indicated the formation of new, smaller compounds (2,4-Diaminopteridine-6-carboxylic acid, N-(4-Aminobenzoyl)-L-glutamic acid, etc.) after drug degradation. The plasma-treated methotrexate solution also showed lower toxicity toward freshwater chlorella algae compared to the untreated solution. Finally, it can be said that non-thermal plasma jets are economically and environmentally friendly devices that have the potential to be used for the treatment of complex and resistive anticancer drug-polluted wastewaters.

14.
Front Oncol ; 13: 1124447, 2023.
Article in English | MEDLINE | ID: mdl-37361603

ABSTRACT

It is well known that patients with cancer have a significantly higher cardiovascular mortality risk than the general population. Cardio-oncology has emerged to focus on these issues including risk reduction, detection, monitoring, and treatment of cardiovascular disease or complications in patients with cancer. The rapid advances in early detection and drug development in oncology, along with socioeconomic differences, racial inequities, lack of support, and barriers to accessing quality medical care, have created disparities in various marginalized populations. In this review, we will discuss the factors contributing to disparities in cardio-oncologic care in distinct populations, including Hispanic/Latinx, Black, Asian and Pacific Islander, indigenous populations, sex and gender minorities, and immigrants. Some factors that contribute to differences in outcomes in cardio-oncology include the prevalence of cancer screening rates, genetic cardiac/oncologic risk factors, cultural stressors, tobacco exposure rates, and physical inactivity. We will also discuss the barriers to cardio-oncologic care in these communities from the racial and socioeconomic context. Appropriate and timely cardiovascular and cancer care in minority groups is a critical component in addressing these disparities, and there need to be urgent efforts to address this widening gap.

15.
Oncologist ; 28(7): 609-617, 2023 07 05.
Article in English | MEDLINE | ID: mdl-37119268

ABSTRACT

INTRODUCTION: Women and underrepresented groups in medicine hold few academic leadership positions in the field of hematology/oncology. In this study, we assessed gender and race/ethnicity representation in editorial board positions in hematology/oncology journals. MATERIALS AND METHODS: Editorial leadership board members from 60 major journals in hematology and oncology were reviewed; 54 journals were included in the final analysis. Gender and race/ethnicity were determined based on publicly available data for Editor-in-Chief (EiC) and Second-in-Command (SiC) (including deputy, senior, or associate editors). Descriptive statistics and chi-squared were estimated. In the second phase of the study, editors were emailed a 4-item survey to self-identify their demographics. RESULTS: Out of 793 editorial board members, 72.6% were men and 27.4% were women. Editorial leadership were non-Hispanic white (71.1%) with Asian editorial board members representing the second largest majority at 22.5%. Women comprised only 15.9% of the EiC positions (90% White and 10% Asian). Women were about half as likely to be in the EiC position compared with men [pOR 0.47 (95% CI, 0.23-0.95, P = .03)]. Women represented 28.3% of SiC editorial positions. Surgical oncology had the lowest female representation at 2.3%. CONCLUSION: Women and minorities are significantly underrepresented in leadership roles on Editorial Boards in hematology/oncology journals. Importantly, the representation of minority women physicians in EiC positions is at an inexorable zero.


Subject(s)
Hematology , Physicians, Women , Male , Humans , Female , Ethnicity , Medical Oncology
16.
J Immunother ; 46(4): 152-153, 2023 05 01.
Article in English | MEDLINE | ID: mdl-36780126

ABSTRACT

Immune checkpoint inhibitors (ICI) are antibodies that block immune checkpoint proteins from binding with their partner proteins on cancer cells, subsequently allowing cytotoxic T-cell-associated enhancement of antitumor responses. Although ICIs have become the standard of care for various malignancies, their use is often limited by unique immune-related adverse events, including dermatologic, endocrine, inflammatory, hepatic, and gastrointestinal events. Diarrhea and colitis are common lower gastrointestinal tract immune-related adverse events, however, only a few cases have reported the association between celiac disease (CD) and ICIs. We report here a case of a 75-year-old man with new onset CD after exposure to the cytotoxic T-lymphocyte-associated antigen-4 ICI, ipilimumab. Although ICI-induced CD is relatively rare, it is essential to consider it in a genetically susceptible patient undergoing treatment with ICI. Patients with known high susceptibility to CD, such as a family history of CD, or with the ancestry of high celiac penetrance (eg, Northern Europe, North Africa, etc), dermatitis herpetiformis, or chronic bowel symptoms, we feel should have celiac panel testing before initiating ICI therapy.


Subject(s)
Antineoplastic Agents, Immunological , Celiac Disease , Neoplasms , Male , Humans , Aged , Immune Checkpoint Inhibitors/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Celiac Disease/chemically induced , Celiac Disease/complications , Celiac Disease/drug therapy , Neoplasms/drug therapy , Ipilimumab/therapeutic use
17.
Cancer Cell ; 41(1): 1-4, 2023 01 09.
Article in English | MEDLINE | ID: mdl-36626866

ABSTRACT

Disparities in cancer care disproportionately impact minority groups, members of which face challenges in accessing high-quality cancer care, remain underrepresented in clinical trials, and experience significant financial toxicity and discrimination during their cancer journey. Diversifying our workforce, improving access to trials, and allocating research funding for equitable initiatives should be prioritized.


Subject(s)
Minority Groups , Neoplasms , Humans , Neoplasms/therapy
18.
J Pediatr Gastroenterol Nutr ; 76(4): 517-522, 2023 04 01.
Article in English | MEDLINE | ID: mdl-36705640

ABSTRACT

OBJECTIVES: Routine gastric aspirate (RGA) monitoring is a common yet controversial practice intended for early identification of gastrointestinal pathology in infants receiving gavage feeds. Our objectives were to evaluate the association of ceasing RGA monitoring on the incidence of necrotizing enterocolitis (NEC) as well as nutritional outcomes in a large population of very low birth weight (VLBW) and very preterm neonates. METHODS: Retrospective record review of neonates born ≤32 weeks and/or VLBW from 2 cohorts: (1) during pre-feed RGA monitoring (September 2015 to June 2018) and (2) after cessation of RGA ("non-RGA") monitoring (July 2018 to December 2020). We compared incidence of NEC, time-to-full enteral feeds, central line duration, and duration of parenteral nutrition (PN) in bivariate and multivariable models accounting for changes in feeding protocols over time. RESULTS: We identified 617 subjects, 53% in the RGA monitoring cohort (n = 327) and 47% in non-RGA cohort (n = 290). The non-RGA cohort had feeds initiated earlier ( P < 0.0001), achieved full enteral feeds more rapidly ( P < 0.0001), received a shorter duration of PN ( P = 0.0003), and had shorter central access duration ( P < 0.0001) without increasing NEC risk. In fact, the non-RGA cohort had a lower incidence of NEC ( P = 0.0345) compared to the RGA cohort. Even after adjusting for changes in feeding protocols over time in a multivariable model, the RGA cohort had significantly higher odds of NEC. CONCLUSIONS: Pre-feed RGA monitoring in the absence of concerning clinical exam findings is not indicated for neonates receiving gavage feeds as it does not improve NEC incidence but instead may delay important nutritional outcomes such as feed initiation and central line removal.


Subject(s)
Enterocolitis, Necrotizing , Infant, Premature, Diseases , Infant, Newborn , Humans , Infant, Premature , Retrospective Studies , Infant, Very Low Birth Weight , Infant, Premature, Diseases/etiology , Time Factors , Enterocolitis, Necrotizing/diagnosis , Enterocolitis, Necrotizing/epidemiology , Enterocolitis, Necrotizing/etiology , Birth Weight
19.
Lancet Respir Med ; 11(6): 563-572, 2023 06.
Article in English | MEDLINE | ID: mdl-36693400

ABSTRACT

BACKGROUND: Patients who have received mechanical ventilation can have prolonged cognitive impairment for which there is no known treatment. We aimed to establish whether early mobilisation could reduce the rates of cognitive impairment and other aspects of disability 1 year after critical illness. METHODS: In this single-centre, parallel, randomised controlled trial, patients admitted to the adult medical-surgical intensive-care unit (ICU), at the University of Chicago (IL, USA), were recruited. Inclusion criteria were adult patients (aged ≥18 years) who were functionally independent and mechanically ventilated at baseline and within the first 96 h of mechanical ventilation, and expected to continue for at least 24 h. Patients were randomly assigned (1:1) via computer-generated permuted balanced block randomisation to early physical and occupational therapy (early mobilisation) or usual care. An investigator designated each assignment in consecutively numbered, sealed, opaque envelopes; they had no further involvement in the trial. Only the assessors were masked to group assignment. The primary outcome was cognitive impairment 1 year after hospital discharge, measured with a Montreal Cognitive Assessment. Patients were assessed for cognitive impairment, neuromuscular weakness, institution-free days, functional independence, and quality of life at hospital discharge and 1 year. Analysis was by intention to treat. This trial was registered with ClinicalTrials.gov, number NCT01777035, and is now completed. FINDINGS: Between Aug 11, 2011, and Oct 24, 2019, 1222 patients were screened, 200 were enrolled (usual care n=100, intervention n=100), and one patient withdrew from the study in each group; thus 99 patients in each group were included in the intention-to-treat analysis (113 [57%] men and 85 [43%] women). 65 (88%) of 74 in the usual care group and 62 (89%) of 70 in the intervention group underwent testing for cognitive impairment at 1 year. The rate of cognitive impairment at 1 year with early mobilisation was 24% (24 of 99 patients) compared with 43% (43 of 99) with usual care (absolute difference -19·2%, 95% CI -32·1 to -6·3%; p=0·0043). Cognitive impairment was lower at hospital discharge in the intervention group (53 [54%] 99 patients vs 68 [69%] 99 patients; -15·2%, -28·6 to -1·7; p=0·029). At 1 year, the intervention group had fewer ICU-acquired weaknesses (none [0%] of 99 patients vs 14 [14%] of 99 patients; -14·1%; -21·0 to -7·3; p=0·0001) and higher physical component scores on quality-of-life testing than did the usual care group (median 52·4 [IQR 45·3-56·8] vs median 41·1 [31·8-49·4]; p<0·0001). There was no difference in the rates of functional independence (64 [65%] of 99 patients vs 61 [62%] of 99 patients; 3%, -10·4 to 16·5%; p=0·66) or mental component scores (median 55·9 [50·2-58·9] vs median 55·2 [49·5-59·7]; p=0·98) between the intervention and usual care groups at 1 year. Seven adverse events (haemodynamic changes [n=3], arterial catheter removal [n=1], rectal tube dislodgement [n=1], and respiratory distress [n=2]) were reported in six (6%) of 99 patients in the intervention group and in none of the patients in the usual care group (p=0·029). INTERPRETATION: Early mobilisation might be the first known intervention to improve long-term cognitive impairment in ICU survivors after mechanical ventilation. These findings clearly emphasise the importance of avoiding delays in initiating mobilisation. However, the increased adverse events in the intervention group warrants further investigation to replicate these findings. FUNDING: None.


Subject(s)
Cognitive Dysfunction , Early Ambulation , Adult , Male , Humans , Female , Adolescent , Early Ambulation/adverse effects , Critical Illness/therapy , Quality of Life , Intensive Care Units , Cognitive Dysfunction/therapy , Cognitive Dysfunction/etiology , Treatment Outcome
20.
Int Urol Nephrol ; 55(3): 503-510, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36462116

ABSTRACT

PURPOSE: Catheter-associated urinary tract infections are of significant medical burden in cost, morbidity, and mortality. Experimental selenium-coated medical devices have demonstrated non-toxic in vitro and in vivo antimicrobial activity. While antimicrobial-coated catheters have shown efficacy in preventing CAUTIs, selenium has not been tested in this context. The purpose of this in vitro study is to evaluate selenium-incorporated urinary catheters for inhibition of uropathogenic bacterial growth and biofilm formation. METHODS: Urinary catheters incorporated with 1% organo-selenium and standard (uncoated) catheters were incubated in vitro with E. coli, K. pneumoniae, P. aeruginosa, H. influenzae, and combinations of these bacteria. Growth was evaluated by colony-forming unit count and visualized with confocal laser and scanning electron microscopy. Organo-selenium catheter material integrity was also tested by soaking the tubing in phosphate-buffered saline for 12 weeks at 37 °C. RESULTS: Organo-selenium-incorporated catheters demonstrated total reduction (100%) of in vitro bacterial growth and biofilm formation for E. coli, K. pneumoniae, H. influenzae, and a combination of these species when compared to control. P. aeruginosa growth was inhibited by approximately 4 logs (99.99%). Complete inhibition of E. coli growth was maintained after long-term phosphate-buffered saline soaking. CONCLUSION: The results demonstrate that organo-selenium was stably incorporated into catheter tubing and inhibited bacterial attachment, growth, and biofilm formation for multiple uropathogenic organisms. Furthermore, long-term soaking of organo-selenium tubing in phosphate-buffered saline did not show any decline in bacterial growth inhibition or biofilm formation. These findings suggest that organo-selenium-incorporated catheters may be advantageous in preventing catheter-associated urinary tract infections and warrant further in vivo and clinical evaluation.


Subject(s)
Anti-Infective Agents , Selenium , Urinary Tract Infections , Humans , Urinary Catheters/microbiology , Escherichia coli , Pseudomonas aeruginosa , Biofilms , Urinary Tract Infections/prevention & control , Bacteria , Phosphates
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