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Journal of Controlled Release :... Jun 2024Vascular diseases constitute a significant contributor to worldwide mortality rates, placing a substantial strain on healthcare systems and socio-economic aspects. They... (Review)
Review
Vascular diseases constitute a significant contributor to worldwide mortality rates, placing a substantial strain on healthcare systems and socio-economic aspects. They are closely associated with inflammatory responses, as sustained inflammation could impact endothelial function, the release of inflammatory mediators, and platelet activation, thus accelerating the progression of vascular diseases. Consequently, directing therapeutic efforts towards mitigating inflammation represents a crucial approach in the management of vascular diseases. Traditional anti-inflammatory medications may have extensive effects on multiple tissues and organs when absorbed through the bloodstream. Conversely, treatments targeting inflammatory vascular diseases, such as monoclonal antibodies, drug-eluting stents, and nano-drugs, can achieve more precise effects, including precise intervention, minimal non-specific effects, and prolonged efficacy. In addition, personalized therapy is an important development trend in targeted therapy for inflammatory vascular diseases. Leveraging advanced simulation algorithms and clinical trial data, treatment strategies are gradually being personalized based on patients' genetic, biomarker, and clinical profiles. It is expected that the application of precision medicine in the field of vascular diseases will have a broader future. In conclusion, targeting therapies offer enhanced safety and efficacy compared to conventional medications; investigating novel targeting therapies and promoting clinical transformation may be a promising direction in improving the prognosis of patients with inflammatory vascular diseases. This article reviews the pathogenesis of inflammatory vascular diseases and presents a comprehensive overview of the potential for targeted therapies in managing this condition.
PubMed: 38945301
DOI: 10.1016/j.jconrel.2024.06.063 -
Contemporary Clinical Trials Jun 2024Awake prone positioning is studied extensively during Covid-19 pandemic, but there is very limited evidence on its utility in acute hypoxic respiratory failure caused by...
BACKGROUND
Awake prone positioning is studied extensively during Covid-19 pandemic, but there is very limited evidence on its utility in acute hypoxic respiratory failure caused by bacterial infections or other causes. The aim of our research is to evaluate the impact of awake prone positioning on outcomes in non-intubated adult patients with acute non-Covid19 hypoxemic respiratory failure.
METHODS
This is a multi-center randomized controlled trial (RCT) with a parallel-group design and a 1:1 allocation ratio. Adult patients, admitted to ICU and diagnosed with hypoxemic respiratory failure will be randomly allocated into intervention (awake prone position (APP)) or control group. Our hypothesis is that addition of awake prone positioning to standard oxygen, high flow oxygen therapy and non-invasive ventilation may reduce the need for mechanical ventilation in adult patients diagnosed with acute hypoxemic respiratory failure. Primary outcome is rate of endotracheal intubation; secondary outcomes include intensive care and hospital mortality, duration of mechanical ventilation, length of intensive care and hospital stay and health related quality of life post hospital discharge. Primary and secondary outcomes will be assessed at hospital discharge, 30, 90 days and 1 year following randomisation.
CONCLUSION
The Hyper-AP study will assess the superiority of awake prone positioning versus standard treatment in spontaneously breathing ICU patients diagnosed with hypoxaemic respiratory failure.
PubMed: 38945293
DOI: 10.1016/j.cct.2024.107614 -
Journal of Dairy Science Jun 2024The primary objective of this study was to evaluate the association between preweaning diarrhea and measures of survival, health and production. The measures of interest...
The primary objective of this study was to evaluate the association between preweaning diarrhea and measures of survival, health and production. The measures of interest included survival (mortality before first calving and time to removal from the herd), health (retained fetal membranes, metritis, mastitis and somatic cell count), and production (305d mature equivalent milk yield and time to first calving). A secondary objective was to investigate if these associations varied according to the age of the calf when the case of diarrhea occurred. Herd records from a farm located in Southern Australia were used to conduct a retrospective cohort study where subjects (calves) with diarrhea were enrolled at the time of their first case along with 2 subjects without diarrhea, matched for age (±3 d) and date of birth (±15 d), amounting to 9833 calves in the data set. Survival analysis was conducted to determine if preweaning diarrhea was associated with death in the short term (first 20 d after enrollment), medium term (21 to 100 d after enrollment) and long-term (101 d after enrollment to first calving). Crude incidence rate ratios, Kaplan-Meier curves and hazard ratios (HR, Cox regression) were derived for each event-based outcome (e.g., death, calving, mastitis). Multivariable linear models were used for continuous outcomes. Calves with preweaning diarrhea had greater mortality rates in the short term (hazard ratio, HR = 2.48, 95% CI: 1.87-3.29) and medium term (HR = 1.89, 95% CI: 1.41-2.55) but not in the long term (HR = 0.98, 95% CI: 0.79-1.22). A small negative association between preweaning diarrhea and time to first calving was found, with calves with diarrhea calving 4 d later than calves without diarrhea (HR = 0.95, 95% CI: 0.91-1.00). Rates of post-calving removal from the herd (death or culling) were higher in calves with a history of preweaning diarrhea (HR = 1.13, 95% CI: 1.01 to 1.26), as were peak lactation log somatic cell count (+0.08, 95% CI: 0.02 to 0.14). Further research is needed to replicate these novel findings as they are based on exploratory analyses and could be spurious findings. No substantial associations were observed for the other measures of interest. Our study findings support existing research demonstrating the significance of preweaning diarrhea as a significant cause of calf mortality, and raises new hypotheses about other potential impacts during lactation.
PubMed: 38945259
DOI: 10.3168/jds.2023-24544 -
Toxicon : Official Journal of the... Jun 2024Morocco is one of the main countries affected in North African with the scorpion envenomations. Faced with the threat, significant morbidity and a major risk of death...
Morocco is one of the main countries affected in North African with the scorpion envenomations. Faced with the threat, significant morbidity and a major risk of death especially in children, a detailed identification of scorpionic profile of stings remains important for health authorities at national or even regional level. The current study aims to establish the epidemiological, clinical, biological and evolutionary data of the scorpionism by analyzing 383 cases of scorpion stings in children from three age groups (< 1 year, 1-5 years and > 5 years), admitted at the Regional Hospital Hassan II-Agadir in the Souss Massa region during the period of 9 years and 10 months from January 2013 to October 2022. Our results showed that patients under 1 year of age presented the most severe cases and had the highest mortality rate. However, the clinical signs and symptoms observed illustrated severe damages to vital systems, particularly the cardiovascular, neurological and pulmonary systems, although the signs associated with the latter were present only in cases admitted in grades 2 and 3 for the three age categories studied. Fluctuations in vital constants (temperature and peripheral oxygen saturation, blood pressure, heart rate and respiratory rate), biochemical parameters (ASAT, ALAT, urea and blood creatine, as well as blood sugar) and CBC results revealed major functional disturbances in vital organs, especially in envenomated cases admitted in grade 3. A positive correlation was mentioned between the state of evolution and the various epidemiological parameters, digestive symptoms, as well as signs and symptoms linked to hemodynamic state, general and neurological state. The main interest is to illustrate the seriousness of scorpion envenomations, especially in the high-risk population, for whom an improved therapeutic approach in health centers will undoubtedly be reinforced, and the admission of immunotherapy, as a fundamental part of the treatment, remains important.
PubMed: 38945218
DOI: 10.1016/j.toxicon.2024.107832 -
Journal of Endodontics Jun 2024The current evidence linking tooth loss and cardiovascular disease mortality is inconclusive. Thus, the aim of this systematic review was to explore the association... (Review)
Review
INTRODUCTION
The current evidence linking tooth loss and cardiovascular disease mortality is inconclusive. Thus, the aim of this systematic review was to explore the association between tooth loss and cardiovascular disease (CVD) mortality.
METHODS
A comprehensive literature search of databases and gray literature included: Web of Science, Scopus, PubMed, CENTRAL, Google Scholar, various digital repositories. The included studies reported on CVD mortality and tooth loss. The Newcastle-Ottawa scale was used to assess the quality of included studies. Random-effects meta-analysis method, sub-group analysis (based on the tooth loss categories (edentulous and fewer than 10 teeth present), meta-regression (based on the number. of confounders), publication bias and sensitivity analysis were performed.
RESULTS
Twelve articles met the eligibility criteria with an overall "Good" quality. A significant association between tooth loss (edentulous or less than 10 teeth present) and CVD mortality was found in the primary meta-analysis, which compiled data from 12 studies. The estimated hazard ratio (HR) was 1.66 (95% CI: 1.32-2.09), and there was high heterogeneity (I = 82.42). Subgroup analysis revealed that the edentulous subgroup showed a higher risk with no significant heterogeneity, while the subgroup with fewer than 10 teeth showed a higher risk with substantial heterogeneity. Meta-regression analysis did not reveal any significant impact (p = 0.626) on whether variations in the number of confounders across studies would substantially affect the overall findings. No publication bias was detected and the sensitivity analysis based on the critical confounders also confirmed that tooth loss as a risk factor for CVD mortality (HR = 1.52, 95% CI: 1.28- 1.80), (I 51.82%).
CONCLUSION
The present systematic review reported that being edentulous or having lesser than 10 teeth is a predictive indicator of CVD mortality.
PubMed: 38945200
DOI: 10.1016/j.joen.2024.06.012 -
Current Problems in Cardiology Jun 2024Current echocardiographic risk factors for prognosis in cardiac amyloidosis (CA) do not distinguish between the two main subtypes: transthyretin cardiomyopathy (TTR) and... (Review)
Review
BACKGROUND
Current echocardiographic risk factors for prognosis in cardiac amyloidosis (CA) do not distinguish between the two main subtypes: transthyretin cardiomyopathy (TTR) and immunoglobulin light chain cardiomyopathy (AL), each of which require distinct diagnostic and therapeutic approaches. Additionally, only traditional parameters have been studied with little data on advanced techniques. Accordingly, we sought to determine whether differences exist in 2D transthoracic echocardiography (2DE) predictors of survival between the CA subtypes using a comprehensive approach.
METHODS
220 patients (72±12 years) with confirmed CA (AL=89, TTR=131) who underwent 2DE at the time of CA diagnosis were enrolled. Left ventricular (LV) dimensions, indexed mass (LVMi), global longitudinal strain (LVGLS), apical-sparing ratio (LVASR), diastology, right ventricular (RV) size and function indices including tricuspid annular systolic excursion (TAPSE), RV free-wall (RVFWS) and global (RVGLS) strain, indexed left (LA) and right atrial volumes (LAVi and RAVi), LA strain (reservoir and booster) and RV systolic pressure (RVSP) were measured. A propensity-score weighted stepwise variable selection Cox proportional hazards model derived from NYHA class and renal impairment status at diagnosis was used to determine the associations between 2DE parameters and mortality specific to CA subtype over a median follow-up of 36-months.
RESULTS
After adjusting for age, atrial fibrillation and treatment, parameters associated with survival were RVFWS (p=0.003, HR 1.15, 95% CI[1.053,1.245]) and RVSP (p=0.03, HR 1.03, 95% CI[1.004,1.063]) in AL and LVASR (p=0.007, HR 6.68, 95% CI[1.75,25.492]) and RAVi (p=0.049, HR 1.03, 95% CI[1.000,1.052]) in TTR.
CONCLUSIONS
Echocardiographic prognosticators for survival are specific to cardiac amyloid subtype. These results potentially provide information critical for clinical decision-making and follow-up in these patients.
PubMed: 38945183
DOI: 10.1016/j.cpcardiol.2024.102729 -
International Journal of Antimicrobial... Jun 2024Polymyxin B, with its unique structure and mechanism of action, has emerged as a key therapeutic agent against Gram-negative bacteria. The study aims to explore...
PURPOSE
Polymyxin B, with its unique structure and mechanism of action, has emerged as a key therapeutic agent against Gram-negative bacteria. The study aims to explore potential factors to influence its effectiveness and safety.
METHODS
A Model-Based Meta-Analysis (MBMA) of 96 articles was conducted, focusing on factors like dosage, bacterial species, and combined antibiotic therapy. The analysis evaluated mortality rates and incidence rate of renal dysfunction, also employing parametric survival models to assess 30-day survival rates.
RESULTS
In the study involving 96 articles and 9,716 patients, polymyxin B's daily dose showed minimal effect on overall mortality, with high-dose group mortality at 33.57% (95% CI: 29.15-38.00) compared to the low-dose group at 35.44% (95% CI: 28.99-41.88), p=0.64. Mortality significantly varied by bacterial species, with Pseudomonas aeruginosa infections at 58.50% (95% CI: 55.42-63.58). Monotherapy exhibited the highest mortality at 40.25% (95% CI: 34.75-45.76), p<0.01. Renal dysfunction was more common in high-dose patients at 29.75% (95% CI: 28.52-30.98), with no significant difference across antibiotic regimens, p=0.54. The 30-day Overall Survival rate for monotherapy therapy was 63.6% (95% CI: 59.3-67.5) and 70.2% (95% CI: 64.4-76.2) for association therapy with β-lactam drugs.
CONCLUSIONS
The dosage of Polymyxin B doesn't significantly change death rates, but its effectiveness varies based on the bacterial infection. Certain bacteria like Pseudomonas aeruginosa are associated with higher mortality. Combining Polymyxin B with other antibiotics, especially β-lactam drugs, improves survival rates. Side effects depend on the dose, with lower doses being safer. These findings emphasize the importance of customizing treatment to balance effectiveness and safety.
PubMed: 38945178
DOI: 10.1016/j.ijantimicag.2024.107262 -
Computer Methods in Biomechanics and... Jun 2024In healthcare settings, Central Venous Catheter-Associated Bloodstream Infections (CVC-BSIs) present a serious problem since they raise morbidity, mortality, and medical...
BACKGROUND
In healthcare settings, Central Venous Catheter-Associated Bloodstream Infections (CVC-BSIs) present a serious problem since they raise morbidity, mortality, and medical expense rates. The management of these illnesses is made more challenging by the development of antimicrobiotic resistance. Nanotechnology has attracted interest recently as a viable method for creating new antimicrobial agents. By putting antibacterial nanomaterials onto the catheter's appear, that may reduce the likelihood of getting sick by stopping germs from adhering and growing. Antimicrobial additives can be released gradually finishes, protecting over time through bioengineering sectors. To prevent and treat CVC-BSIs, this study will assess the efficacy of antimicrobial medicines based on nanoparticles.
METHODS
In the network Meta-Analyses (MA) and Systematic Review (SR), we looked for studies published from January 2010 to September 2021 using the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, MEDLINE, CINAHL, and Web of Science databases. Ten papers in all were included in the review following the screening of the publications using inclusion and exclusion criteria.
RESULTS
In contrast to conventional catheters, the implementation of Antimicrobial Catheters (AC) and the use of chlorhexidine (CHG) or Silver Sulfadiazine (SS) demonstrated notably reduced occurrences of Central Venous Catheter-Associated Bloodstream Infections (CVC-BSIs) per 1000 Catheter Days (CD) (with Odds Ratios (ORs) and 95% Credibility Intervals (CrIs) of 0.66 and 0.54, respectively) by bioengineering sectors. Moreover, these interventions were linked to the lowest rate of Catheter Colonization (CC), with ORs as well as 95% CrIs of 0.45 and 0.31, respectively, underscoring their potential as effective strategies for minimizing the risk of infections associated with catheter use as well as bioengineering sectors innovations.
CONCLUSIONS
As a result, CVC-BSI has shown significant promise for prevention and treatment with nanoparticle-based antimicrobial medicines. Due to their special characteristics and modes of action, they are strong candidates for improving the security and effectiveness of central venous catheter use in clinical settings. Due to ongoing research and development in this area, nanoparticle-based coatings and therapies may be used to lessen the impact of CVC-BSIs and enhance patient outcomes.
PubMed: 38945158
DOI: 10.1080/10255842.2024.2310076 -
The Lancet. Rheumatology Jun 2024Autoimmune rheumatic diseases have distinct pathogenic mechanisms and are causes of disability and increased mortality worldwide. In this study, we aimed to examine...
Annual trends in pain management modalities in patients with newly diagnosed autoimmune rheumatic diseases in the USA from 2007 to 2021: an administrative claims-based study.
BACKGROUND
Autoimmune rheumatic diseases have distinct pathogenic mechanisms and are causes of disability and increased mortality worldwide. In this study, we aimed to examine annual trends in pain management modalities among patients with autoimmune rheumatic diseases.
METHODS
We identified newly diagnosed patients with ankylosing spondylitis, psoriatic arthritis, rheumatoid arthritis, Sjögren's syndrome, systemic sclerosis, or systemic lupus erythematosus (SLE) in the Merative Marketscan Research Databases from 2007 to 2021. The database includes deidentified inpatient and outpatient health encounters with employment-sponsored health insurance claims in the USA. We found minimal occurrences of multiple overlapping conditions and included only the initial recorded diagnosis for each patient. We determined the annual incidence of patients treated with opioids, anticonvulsants, antidepressants, skeletal muscle relaxants, non-steroidal anti-inflammatory drugs (NSAIDs), topical analgesics, and physical therapy in the year following diagnosis. Logistic regression was used to estimate the association between calendar year and outcomes, adjusted for age, sex, and region.
FINDINGS
We included 141 962 patients: 10 927 with ankylosing spondylitis, 21 438 with psoriatic arthritis, 71 393 with rheumatoid arthritis, 16 718 with Sjögren's syndrome, 18 018 with SLE, and 3468 with systemic sclerosis. 107 475 (75·7%) were women and 34 487 (24·3%) were men. Overall, the incidence of opioid use increased annually until 2014 by 4% (adjusted odds ratio [aOR] 1·04 [95% CI 1·03-1·04]) and decreased annually by 15% after 2014 (0·85 [0·84-0·86]). The incidence of physical therapy use increased annually by 5% until 2014 (aOR 1·05 [95% CI 1·04-1·06]), with a slight decrease annually by 1% after 2014 (0·99 [0·98-1·00]). The incidence of anticonvulsant use increased annually by 7% until 2014 (aOR 1·07 [95% CI 1·07-1·08]) and did not significantly change after 2014 (1·00 [0·99-1·00]). Before 2014, the incidence of NSAIDs use increased by 2% annually (aOR 1·02 [95% CI 1·02-1·03]); however, after 2014, the incidence decreased annually by 5% (0·95 [0·95-0·96]). These trends did not differ by sex except for NSAID use before 2014 (p=0·02) and topical analgesic use after 2014 (p=0·0100).
INTERPRETATION
Since 2014, the use of non-opioid pain management modalities has increased or stabilised, whereas opioid and NSAID use has declined. Future studies are needed to evaluate the effectiveness of these changes, and the effects they have had on outcomes such as quality of life, disability, and function.
FUNDING
National Institute of Arthritis and Musculoskeletal and Skin Diseases.
PubMed: 38945137
DOI: 10.1016/S2665-9913(24)00120-6 -
The Lancet. Healthy Longevity Jul 2024Little is known about ageing and frailty progression in low-income settings. We aimed to describe frailty changes over time in individuals living in rural Burkina Faso...
BACKGROUND
Little is known about ageing and frailty progression in low-income settings. We aimed to describe frailty changes over time in individuals living in rural Burkina Faso and to assess which sociodemographic, disability, and multimorbidity factors are associated with frailty progression and mortality.
METHODS
This longitudinal, population-based study was conducted at the Nouna Health and Demographic Surveillance Systems (HDSS) site in northwestern Burkina Faso. Eligible participants were aged 40 years or older and had been primarily resident in a household within the HDSS area for at least the past 6 months before the baseline survey and were selected from the 2015 HDSS household census using a stratified random sample of adults living in unique households within the area. Participants were interviewed in their homes in 2018 (baseline), 2021 (follow-up), or both. We derived the Fried frailty score for each participant at each timepoint using data on grip strength, gait speed, self-reported weight loss, self-reported exhaustion, and physical activity, and described changes in frailty status (no frailty, pre-frailty, or frailty) between 2018 and 2021. We used multivariate regression models to assess factors (ie, sex, age, marital status, educational attainment, wealth quintile, WHO Disability Assessment Schedule (WHODAS) score, and multimorbidity) associated with frailty progression (either worsening frailty status or dying, compared with frailty status remaining the same or improving) and with mortality, and developed sequential models: unadjusted, adjusting for sociodemographic factors (sex, age, marital status, educational attainment, and wealth quintile), and adjusting for sociodemographic factors, disability, and multimorbidity.
FINDINGS
Between May 25 and July 19, 2018, and between July 1 and Aug 22, 2021, 5952 individuals were invited to participate: 1709 (28·7%) did not consent, 1054 (17·8%) participated in 2018 only and were lost to follow-up, 1214 (20·4%) participated in 2021 only, and 1975 (33·2%) were included in both years or died between years. Of 1967 participants followed up with complete demographic data, 190 (9·7%) were frail or unable to complete the frailty assessment in 2018, compared with 77 (3·9%) in 2021. Between 2018 and 2021, frailty status improved in 567 (28·8%) participants and worsened in 327 (16·6%), and 101 (5·1%) participants died. The relative risk of frailty status worsening or of dying (compared with frailty impRoving or no change) increased with age and WHODAS score, whereas female sex appeared protective. After controlling for all sociodemographic factors, multimorbidity, and WHODAS score, odds of mortality were 1·07 (odds ratio 2·07, 95% CI 1·05-4·09) times higher among pre-frail individuals and 1·1 (2·21, 0·90-5·41) times higher among frail individuals than among non-frail individuals.
INTERPRETATION
Frailty status was highly dynamic in this low-income setting and appears to be modifiable. Given the rapid increase in the numbers of older adults in low-income or middle-income countries, understanding the behaviour of frailty in these settings is of high importance for the development of policies and health systems to ensure the maintenance of health and wellbeing in ageing populations. Future work should focus on designing context-appropriate interventions to improve frailty status.
FUNDING
Alexander Von Humboldt Foundation, Institute for Global Innovation, University of Birmingham, and Wellcome Trust.
Topics: Humans; Male; Female; Longitudinal Studies; Aged; Middle Aged; Frailty; Burkina Faso; Rural Population; Adult; Disease Progression; Aged, 80 and over; Frail Elderly
PubMed: 38945131
DOI: 10.1016/S2666-7568(24)00096-5