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Knowledge, attitudes, and practices about HIV and other sexually transmitted infections among High School students in Southern Italy: A cross-sectional survey

by Francesco Di Gennaro, Francesco Vladimiro Segala, Giacomo Guido, Mariacristina Poliseno, Laura De Santis, Alessandra Belati, Carmen Rita Santoro, Irene Francesca Bottalico, Carmen Pellegrino, Roberta Novara, Luisa Frallonardo, Mariangela Cormio, Michele Camporeale, Sergio Cotugno, Vincenzo Giliberti, Stefano Di Gregorio, Valentina Totaro, Nicola Catucci, Anna De Giosa, Roberta Giusto, Ilaria Viviana Lanera, Gioacchino Angarano, Sergio Lo Caputo, Annalisa Saracino

High School students, recognized as a high-risk group for sexually transmitted infections (STIs), were the focal point of an educational campaign in Southern Italy to share information and good practices about STIs and HIV/AIDS. A baseline survey comprising 76 items was conducted via the REDCap platform to assess students’ initial knowledge, attitudes, and practices (KAP) related to STIs and HIV/AIDS. Sociodemographic variables were also investigated. The association between variables and KAP score was assessed by Kruskal-Wallis’ or Spearman’s test, as appropriate. An ordinal regression model was built to estimate the effect size, reported as odds ratio (OR) with a 95% confidence interval (CI), for achieving higher KAP scores among students features. On a scale of 0 to 29, 1702 participants achieved a median KAP score of 14 points. Higher scores were predominantly reported by students from classical High Schools (OR 3.19, 95% C.I. 1.60–6.33, p

Tobacco price elasticity by socioeconomic characteristics in Ecuador

by Ana Cristina Mena, Guillermo Paraje

Smoking is a worldwide epidemic and increased prices are one of the most cost-effective measures to reduce tobacco consumption. This article aims to estimate the price and income elasticity of cigarettes for different population groups in Ecuador. The National Survey of Urban and Rural Household Income and Expenditures (ENIGHUR) 2011–2012 was used, which has information on household cigarette consumption and its sociodemographic characteristics. Deaton’s Almost Ideal Demand System, which decouples the effect of quality on the price of the good, was applied. The elasticities were calculated for several groups: urban/rural, income levels (tertiles), education level, sex and age ranges of the household head, and frequency of cigarette purchases in households. The estimated price elasticity nationwide is -0.89 and the income elasticity is 0.41, both statistically significant. Households headed by women (-2.22) are more sensitive to an increase in cigarette prices than those headed by men (-0.65) and households headed by people between 20 and 40 years of age (-2.32) have a higher price elasticity compared to country-level estimations. Differences within other groups are not statistically significant.

Test-retest reliability of Latin American Group for Maturity (GDLAM) protocol in older women

by Álvaro Huerta Ojeda, Emilio Jofré-Saldía, Jimena Arriagada Molina, Patricia Rojas Quinchavil, María Paz Parada Toledo, Sergio Galdames Maliqueo, María-Mercedes Yeomans-Cabrera, Carlos Jorquera-Aguilera, Frano Giakoni-Ramirez, Maximiliano Bravo

Functional autonomy (FA) is a critical factor in determining the quality of life of older adults (OA), especially in the case of older women (OW), as they face a decline in FA in their later years of life. FA should be assessed early, using valid, reliable, and low-cost tests. This study evaluated the test-retest reliability of GDLAM and GDLAM autonomy index (GI) in OW. Thirty-nine OW (71.2 ± 6.50 years) participated in the study. A repeated measures design was used to compare the interday test-retest reliability of the five GDLAM tests (seconds) and the GI (points). The five tests represent activities of daily living, such as dressing or wandering around the house, while the GI provides a weighting of the results of the five tests. The analysis consisted of the intraclass correlation coefficient (ICC), standard error of measurement (SEM), and coefficient of variation (CV). A CV ≤ 10% and an ICC ≥ 0.80 were considered acceptable reliability, whereas a CV ≤ 5% and an ICC ≥ 0.90 were considered high reliability. The outcome of the five tests, represented by the GI, showed high interday test-retest reliability (CV = 6.00% and ICC = 0.91). The results of this study demonstrate that the five tests of the GDLAM protocol and the GI have high interday test-retest reliability and good interday reproducibility. From a practical point of view, the GDLAM protocol allows the assessment of FA of community-dwelling OW, providing background for early diagnosis and, with it, the possibility of developing an individualized physical exercise prescription.

<i>Spilanthes filicaulis</i> (Schumach. & Thonn.) C.D. Adams leaves protects against streptozotocin-induced diabetic nephropathy

by Oluwafemi Adeleke Ojo, Akingbolabo Daniel Ogunlakin, Christopher Oloruntoba Akintayo, Olaoluwa Sesan Olukiran, Juliana Bunmi Adetunji, Omolola Adenike Ajayi-Odoko, Theophilus Oghenenyoreme Ogwa, Olorunfemi Raphael Molehin, Omolara Olajumoke Ojo, Ramzi A. Mothana, Abdullah R. Alanzi

Background and objective

Diabetic neuropathy (DN) is a complex type of diabetes. The underlying cause of diabetic nephropathy remains unclear and may be due to a variety of pathological conditions resulting in kidney failure. This study examines the protective effect of the methanolic extract of Spilanthes filicaulis leaves (MESFL) in fructose-fed streptozotocin (STZ)-induced diabetic nephropathy and the associated pathway.

Methods

Twenty-five rats were equally divided randomly into five categories: Control (C), diabetic control, diabetic + metformin (100 mg/kg), diabetic + MESFL 150 mg/kg bw, and diabetic + MESFL 300 mg/kg bw. After 15 days, the rats were evaluated for fasting blood glucose (FBG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), urea, uric acid, serum creatinine, reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation (MDA). Gene expression levels of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP response element-binding (CREB), cFOS and the antiapoptotic protein Bcl-2 were examined.

Results

We observed that MESFL at 150 and 300 mg/kg bw significantly downregulated the protein expression of cAMP, PKA, CREB, and cFOS and upregulated the Bcl-2 gene, suggesting that the nephroprotective action of MESFL is due to the suppression of the cAMP/PKA/CREB/cFOS signaling pathway. In addition, MESFL increases SOD and CAT activities and GSH levels, reduces MDA levels, and reduces renal functional indices (ALP, urea, uric acid, and creatinine).

Conclusion

Therefore, our results indicate that MESFL alleviates the development of diabetic nephropathy via suppression of the cAMP/PKA/CREB/cFOS pathways.

Effects of (2<i>R</i>,6<i>R</i>)-hydroxynorketamine in assays of acute pain-stimulated and pain-depressed behaviors in mice

by Todd M. Hillhouse, Kaitlyn J. Partridge, Patrick I. Garrett, Sarah C. Honeycutt, Joseph H. Porter

Ketamine has been shown to produce analgesia in various acute and chronic pain states; however, abuse liability concerns have limited its utility. The ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) has been shown to produce antidepressant-like effects similar to ketamine without abuse liability concerns. (2R,6R)-HNK produces sustained analgesia in models of chronic pain, but has yet to be evaluated in models of acute pain. The present study evaluated the efficacy of acute (2R,6R)-HNK administration (one injection) in assays of pain-stimulated (52- and 56-degree hot plate test and acetic acid writhing) and pain-depressed behavior (locomotor activity and rearing) in male and female C57BL/6 mice. In assays of pain-stimulated behaviors, (2R,6R)-HNK (1–32 mg/kg) failed to produce antinociception in the 52- and 56-degree hot plate and acetic acid writhing assays. In assays of pain-depressed behaviors, 0.56% acetic acid produced a robust depression of locomotor activity and rearing that was not blocked by pretreatment of (2R,6R)-HNK (3.2–32 mg/kg). The positive controls morphine (hot plate test) and ketoprofen (acetic acid writhing, locomotor activity, and rearing) blocked pain-stimulated and pain-depressed behaviors. Finally, the effects of intermittent (2R,6R)-HNK administration were evaluated in 52-degree hot plate and pain-depressed locomotor activity and rearing. Intermittent administration of (2R,6R)-HNK also did not produce antinociceptive effects in the hot plate or pain-depressed locomotor activity assays. These results suggest that (2R,6R)-HNK is unlikely to have efficacy in treating acute pain; however, the efficacy of (2R,6R)-HNK in chronic pain states should continue to be evaluated.

A bilateral filtering-based image enhancement for Alzheimer disease classification using CNN

by Nicodemus Songose Awarayi, Frimpong Twum, James Ben Hayfron-Acquah, Kwabena Owusu-Agyemang

This study aims to develop an optimally performing convolutional neural network to classify Alzheimer’s disease into mild cognitive impairment, normal controls, or Alzheimer’s disease classes using a magnetic resonance imaging dataset. To achieve this, we focused the study on addressing the challenge of image noise, which impacts the performance of deep learning models. The study introduced a scheme for enhancing images to improve the quality of the datasets. Specifically, an image enhancement algorithm based on histogram equalization and bilateral filtering techniques was deployed to reduce noise and enhance the quality of the images. Subsequently, a convolutional neural network model comprising four convolutional layers and two hidden layers was devised for classifying Alzheimer’s disease into three (3) distinct categories, namely mild cognitive impairment, Alzheimer’s disease, and normal controls. The model was trained and evaluated using a 10-fold cross-validation sampling approach with a learning rate of 0.001 and 200 training epochs at each instance. The proposed model yielded notable results, such as an accuracy of 93.45% and an area under the curve value of 0.99 when trained on the three classes. The model further showed superior results on binary classification compared with existing methods. The model recorded 94.39%, 94.92%, and 95.62% accuracies for Alzheimer’s disease versus normal controls, Alzheimer’s disease versus mild cognitive impairment, and mild cognitive impairment versus normal controls classes, respectively.

Self-administration medication errors at home and its predictors among illiterate and low-literate community-dwelling older adults with polypharmacy: A negative binomial hierarchical regression

by Nafiseh Ghassab-Abdollahi, Haidar Nadrian, Elnaz Shaseb, Narges Kheirollahi, Mina Hashemiparast

Background

Older adults with polypharmacy are more prone to medication errors. People with low educational attainment have more difficulties in taking their medications.

Objectives

This study aimed to identify the extent of medication self-administration errors (MSEs) and the contributing factors among illiterate and low-literate community-dwelling older adults with polypharmacy.

Method

The present cross-sectional study was conducted among people aged 60 and above. The data were collected using the sociodemographic, clinical, and Belief about Medicines Questionnaires (BMQ). To determine the extent of MSE, a medication error checklist was used. The negative binomial hierarchical regression model in the five blocks was performed.

Results

The final sample size was 276 people. The frequency of MSEs in the last 6 months was 69.2%. Sixteen percent of participants had made four or more mistakes. The most common MSEs were forgetting, improper taking of medications with food, improper timing, incorrect dosage (lower dose), and forgetting the doctor’s instructions. Near 18% of participants reported adverse events following their mistakes. The significant predictors of MSEs were being completely illiterate (p = 0.021), the higher number of doctor visits per year (p = 0.014), irregularly seeing doctors (p Conclusion

Despite the high prevalence of MSEs among older patients, practical strategies to deal with them at their homes have not been established among health systems. MSE as a multifactorial event can be caused by a collection of internal and external factors. Further studies to identify the role of patients, clinicians, procedures, and systems in developing MSEs as interconnected components are needed.

Participant recruitment and attrition in surgical randomised trials with placebo controls versus non-operative controls: a meta-epidemiological study and meta-analysis

Por: Natarajan · P. · Menounos · S. · Harris · L. · Monuja · M. · Gorelik · A. · Karjalainen · T. · Buchbinder · R. · Harris · I. A. · Naylor · J. M. · Adie · S.
Objective

To compare differences in recruitment and attrition between placebo control randomised trials of surgery, and trials of the same surgical interventions and conditions that used non-operative (non-placebo) controls.

Design

Meta-epidemiological study.

Data sources

Randomised controlled trials were identified from an electronic search of MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials from their inception date to 21 November 2018.

Study selection

Placebo control trials evaluating efficacy of any surgical intervention and non-operative control trials of the same surgical intervention were included in this study. 25 730 records were retrieved from our systemic search, identifying 61 placebo control and 38 non-operative control trials for inclusion in analysis.

Outcome measures

Primary outcome measures were recruitment and attrition. These were assessed in terms of recruitment rate (number of participants enrolled, as a proportion of those eligible) and overall attrition rate (composite of dropout, loss to follow-up and cross-overs, expressed as proportion of total sample size). Secondary outcome measures included participant cross-over rate, dropout and loss to follow-up.

Results

Unadjusted pooled recruitment and attrition rates were similar between placebo and non-operative control trials. Study characteristics were not significantly different apart from time to primary timepoint which was shorter in studies with placebo controls (365 vs 274 days, p=0.006). After adjusting for covariates (follow-up duration and number of timepoints), the attrition rate of placebo control trials was almost twice as high compared with non-operative controlled-trials (incident rate ratio (IRR) (95% CI) 1.8 (1.1 to 3.0), p=0.032). The incorporation of one additional follow-up timepoint (regardless of follow-up duration) was associated with reduced attrition in placebo control surgical trials (IRR (95% CI) 0.64 (0.52 to 0.79), p

Conclusions

Placebo control trials of surgery have similar recruitment issues but higher attrition compared with non-operative (non-placebo) control trials. Study design should incorporate strategies such as increased timepoints for given follow-up duration to mitigate losses to follow-up and dropout.

PROSPERO registration number

CRD42019117364.

COVID-19 vaccine acceptance in the general population and under-resourced communities from high-income countries: realist review

Por: Gonzalez-Jaramillo · N. · Abbühl · D. · Roa-Diaz · Z. M. · Kobler-Betancourt · C. · Frahsa · A.
Objective

To compare vaccination willingness before rollout and 1 year post-rollout uptake among the general population and under-resourced communities in high-income countries.

Design

A realist review.

Data sources

Embase, PubMed, Dimensions ai and Google Scholar.

Setting

High-income countries.

Definitions

We defined vaccination willingness as the proportion of participants willing or intending to receive vaccines prior to availability. We defined vaccine uptake as the real proportion of the population with complete vaccination as reported by each country until November 2021.

Results

We included data from 62 studies and 18 high-income countries. For studies conducted among general populations, the proportion of vaccination willingness was 67% (95% CI 62% to 72%). In real-world settings, the overall proportion of vaccine uptake among those countries was 73% (95% CI 69% to 76%). 17 studies reported pre-rollout willingness for under-resourced communities. The summary proportion of vaccination willingness from studies reporting results among people from under-resourced communities was 52% (95% CI 0.46% to 0.57%). Real-world evidence about vaccine uptake after rollout among under-resourced communities was limited.

Conclusion

Our review emphasises the importance of realist reviews for assessing vaccine acceptance. Limited real-world evidence about vaccine uptake among under-resourced communities in high-income countries is a call to context-specific actions and reporting.

Restrictive use of Restraints and Delirium Duration in the Intensive Care Unit (R2D2-ICU): protocol for a French multicentre parallel-group open-label randomised controlled trial

Por: Sonneville · R. · Couffignal · C. · Sigaud · F. · Godard · V. · Audibert · J. · Contou · D. · Celier · A. · Djibre · M. · Schmidt · J. · Jaquet · P. · Mekontso Dessap · A. · Bourel · C. · Bellot · R. · Roy · C. · Lamara · F. · Essardy · F. · Timsit · J.-F. · Cornic · R. · Bouadma · L. · On b
Introduction

Physical restraint (PR) is prescribed in patients receiving invasive mechanical ventilation in the intensive care unit (ICU) to avoid unplanned removal of medical devices. However, it is associated with an increased risk of delirium. We hypothesise that a restrictive use of PR, as compared with a systematic use, could reduce the duration of delirium in ICU patients receiving invasive mechanical ventilation.

Methods and analysis

The Restrictive use of Restraints and Delirium Duration in ICU (R2D2-ICU) study is a national multicentric, parallel-group, randomised (1:1) open-label, controlled, superiority trial, which will be conducted in 10 ICUs. A total of 422 adult patients requiring invasive mechanical ventilation for an expected duration of at least 48 hours and eligible for prescription of PR will be randomly allocated within 6 hours from intubation to either the restrictive PR use group or the systematic PR use group, until day 14, ICU discharge or death, whichever comes first. In both groups, PR will consist of the use of wrist straps. The primary endpoint will be delirium or coma-free days, defined as the number of days spent alive in the ICU without coma or delirium within the first 14 days after randomisation. Delirium will be assessed using the Confusion Assessment Method-ICU twice daily. Key secondary endpoints will encompass agitation episodes, opioid, propofol, benzodiazepine and antipsychotic drug exposure during the 14-day intervention period, along with a core outcome set of measures evaluated 90 days postrandomisation.

Ethics and dissemination

The R2D2-ICU study has been approved by the Comité de Protection des Personnes (CPP) ILE DE FRANCE III—PARIS (CPP19.09.06.37521) on June 10th, 2019). Participant recruitment started on 25 January 2021. Results will be published in international peer-reviewed medical journals and presented at conferences.

Trial registration number

NCT04273360.

Outcomes after cancer diagnosis in children and adult patients with congenital heart disease in Sweden: a registry-based cohort study

Por: Karazisi · C. · Dellborg · M. · Mellgren · K. · Giang · K. W. · Skoglund · K. · Eriksson · P. · Mandalenakis · Z.
Objective

Patients with congenital heart disease (CHD) have an increased cancer risk. The aim of this study was to determine cancer-related mortality in CHD patients compared with non-CHD controls, compare ages at cancer diagnosis and death, and explore the most fatal cancer diagnoses.

Design

Registry-based cohort study.

Setting and participants

CHD patients born between 1970 and 2017 were identified using Swedish Health Registers. Each was matched by birth year and sex with 10 non-CHD controls. Included were those born in Sweden with a cancer diagnosis.

Results

Cancer developed in 758 out of 67814 CHD patients (1.1%), with 139 deaths (18.3%)—of which 41 deaths occurred in patients with genetic syndromes. Cancer was the cause of death in 71.9% of cases. Across all CHD patients, cancer accounted for 1.8% of deaths. Excluding patients with genetic syndromes and transplant recipients, mortality risk between CHD patients with cancer and controls showed no significant difference (adjusted HR 1.17; 95% CI 0.93 to 1.49). CHD patients had a lower median age at cancer diagnosis—13.0 years (IQR 2.9–30.0) in CHD versus 24.6 years (IQR 8.6–35.1) in controls. Median age at death was 15.1 years (IQR 3.6–30.7) in CHD patients versus 18.5 years (IQR 6.1–32.7) in controls. The top three fatal cancer diagnoses were ill-defined, secondary and unspecified, eye and central nervous system tumours and haematological malignancies.

Conclusions

Cancer-related deaths constituted 1.8% of all mortalities across all CHD patients. Among CHD patients with cancer, 18.3% died, with cancer being the cause in 71.9% of cases. Although CHD patients have an increased cancer risk, their mortality risk post-diagnosis does not significantly differ from non-CHD patients after adjustements and exclusion of patients with genetic syndromes and transplant recipients. However, CHD patients with genetic syndromes and concurrent cancer appear to be a vulnerable group.

Randomised controlled, patient-blinded, multicentre, superiority trial to evaluate the efficacy of the line-attached sheath-type traction device for endoscopic submucosal dissection in patients with superficial gastric neoplasms

Por: Abe · H. · Sako · T. · Yamamoto · Y. · Ikeda · A. · Kawara · F. · Ose · T. · Takao · T. · Kitamura · Y. · Ariyoshi · R. · Morita · Y. · Ishida · T. · Ikegawa · T. · Ishida · R. · Yoshizaki · T. · Sakaguchi · H. · Toyonaga · T. · Kodama · Y.
Introduction

EndoTrac is a line-attached sheath-type traction device that enables us to control the direction and the force of traction during endoscopic submucosal dissection (ESD). The efficacy of EndoTrac for gastric ESD has not been fully verified.

Methods and analysis

The G-Trac study is a multicentre (nine general hospitals and two university hospitals in Japan) collaborative trial assessing the efficacy of EndoTrac for gastric ESDs. Patients with superficial gastric neoplasms will be enrolled and randomly assigned to undergo either conventional ESD or EndoTrac ESD. Allocation will be stratified according to tumour location, operator experience and tumour diameter at an allocation rate of 1:1. The type of endoknife used will be confirmed before randomisation. The primary outcome, procedure time, will be compared between the groups in both intention-to-treat and per-protocol analyses using the Wilcoxon rank sum test. The efficacy-related, safety-related and device-related outcomes will be assessed in the secondary analysis. The planned sample size of the 142 patients in the two groups will enable us to detect a difference with a power of 80% by using the Wilcoxon rank sum test, assuming an effect size of 0.54, asymptotic relative efficiency of 0.864 and a two-sided type 1 error rate of 5%.

Ethics and dissemination

This trial was approved by the certified review board of Kobe University (22 December 2022). The results from this trial will be disseminated through peer-review journals, presentations at national and international conferences, and data sharing with other researchers.

Trial registration number

jRCT1052220166.

Skin closUre in carPal tunnEl Release (SUPER): protocol for a blinded randomised controlled trial comparing absorbable and non-absorbable sutures in carpal tunnel release

Por: Savolainen · A. · Nietosvaara · Y. · Sirola · J. · Hytönen · M. · Reito · A. · Heikkinen · N. · Räisänen · M. P.
Introduction

Carpal tunnel syndrome is a common disorder affecting a substantial portion of the general population. Surgical intervention is often deemed necessary, with the median nerve release being one of the most frequent operations. Optimising all the aspects of this procedure can enhance patient satisfaction with the treatment.

Methods and analysis

We aim to determine the differences in the aesthetic outcome of the scar as well as the pain experienced during the healing process between the use of absorbable and non-absorbable sutures. The primary outcome measure will be the patients’ subjective satisfaction with the aesthetic appearance of the scar 1 year after the operation. Secondary outcomes will include a similar evaluation of the aesthetics performed by a blinded outcome assessor, as well as pain experienced by the patients during the 2 weeks postoperatively. The severity and improvement of the patients’ symptoms will also be measured by a Finnish version of the Boston Carpal Tunnel Questionnaire. Costs will be evaluated for both groups. Safety of the wound closure will be followed and reported.

Ethics and dissemination

This protocol was approved by the Research Ethics Committee of the Northern Savo Hospital District (2319/2021). The trial will be conducted in accordance with the principles of Good Clinical Practice and the Declaration of Helsinki. The results will be disseminated through publication in peer-reviewed journals.

Trial registration number

NCT05503719.

Study protocol: improving response to malaria in the Amazon through identification of inter-community networks and human mobility in border regions of Ecuador, Peru and Brazil

Por: Janko · M. M. · Araujo · A. L. · Ascencio · E. J. · Guedes · G. R. · Vasco · L. E. · Santos · R. O. · Damasceno · C. P. · Medrano · P. G. · Chacon-Uscamaita · P. R. · Gunderson · A. K. · OMalley · S. · Kansara · P. H. · Narvaez · M. B. · Coombes · C. · Pizzitutti · F. · Salmon-Mulano
Introduction

Understanding human mobility’s role in malaria transmission is critical to successful control and elimination. However, common approaches to measuring mobility are ill-equipped for remote regions such as the Amazon. This study develops a network survey to quantify the effect of community connectivity and mobility on malaria transmission.

Methods

We measure community connectivity across the study area using a respondent driven sampling design among key informants who are at least 18 years of age. 45 initial communities will be selected: 10 in Brazil, 10 in Ecuador and 25 in Peru. Participants will be recruited in each initial node and administered a survey to obtain data on each community’s mobility patterns. Survey responses will be ranked and the 2–3 most connected communities will then be selected and surveyed. This process will be repeated for a third round of data collection. Community network matrices will be linked with each country’s malaria surveillance system to test the effects of mobility on disease risk.

Ethics and dissemination

This study protocol has been approved by the institutional review boards of Duke University (USA), Universidad San Francisco de Quito (Ecuador), Universidad Peruana Cayetano Heredia (Peru) and Universidade Federal Minas Gerais (Brazil). Results will be disseminated in communities by the end of the study.

The role of orthobiologics in chronic wound healing

Abstract

Chronic wounds, characterized by prolonged healing processes, pose a significant medical challenge with multifaceted aetiologies, including local and systemic factors. Here, it explores the complex pathogenesis of chronic wounds, emphasizing the disruption in the normal phases of wound healing, particularly the inflammatory phase, leading to an imbalance in extracellular matrix (ECM) dynamics and persistent inflammation. Senescent cell populations further contribute to impaired wound healing in chronic lesions. Traditional medical management focuses on addressing underlying causes, but many chronic wounds resist to conventional treatments, necessitating innovative approaches. Recent attention has turned to autologous orthobiologics, such as platelet-rich plasma (PRP), platelet-rich fibrin (PRF) and mesenchymal stem cells (MSCs), as potential regenerative interventions. These biologically derived materials, including bone marrow aspirate/concentrate (BMA/BMAC) and adipose tissue-derived stem cells (ADSCs), exhibit promising cytokine content and regenerative potential. MSCs, in particular, have emerged as key players in wound healing, influencing inflammation and promoting tissue regeneration. This paper reviews relevant scientific literature regarding basic science and brings real-world evidence regarding the use of orthobiologics in the treatment of chronic wounds, irrespective of aetiology. The discussion highlights the regenerative properties of PRP, PRF, BMA, BMAC and SVF, showcasing their potential to enhance wound healing. Despite advancements, further research is essential to elucidate the specific roles of each orthobiologic and determine optimal applications for different wound types. The conclusion underscores the evolving landscape in chronic wound management, with a call for more comprehensive studies to refine treatment strategies and maximize the benefits of regenerative medicine.

Development of an enhanced scoring system to predict ICU readmission or in-hospital death within 24 hours using routine patient data from two NHS Foundation Trusts

Por: Pimentel · M. A. F. · Johnson · A. · Darbyshire · J. L. · Tarassenko · L. · Clifton · D. A. · Walden · A. · Rechner · I. · Watkinson · P. J. · Young · J. D.
Rationale

Intensive care units (ICUs) admit the most severely ill patients. Once these patients are discharged from the ICU to a step-down ward, they continue to have their vital signs monitored by nursing staff, with Early Warning Score (EWS) systems being used to identify those at risk of deterioration.

Objectives

We report the development and validation of an enhanced continuous scoring system for predicting adverse events, which combines vital signs measured routinely on acute care wards (as used by most EWS systems) with a risk score of a future adverse event calculated on discharge from the ICU.

Design

A modified Delphi process identified candidate variables commonly available in electronic records as the basis for a ‘static’ score of the patient’s condition immediately after discharge from the ICU. L1-regularised logistic regression was used to estimate the in-hospital risk of future adverse event. We then constructed a model of physiological normality using vital sign data from the day of hospital discharge. This is combined with the static score and used continuously to quantify and update the patient’s risk of deterioration throughout their hospital stay.

Setting

Data from two National Health Service Foundation Trusts (UK) were used to develop and (externally) validate the model.

Participants

A total of 12 394 vital sign measurements were acquired from 273 patients after ICU discharge for the development set, and 4831 from 136 patients in the validation cohort.

Results

Outcome validation of our model yielded an area under the receiver operating characteristic curve of 0.724 for predicting ICU readmission or in-hospital death within 24 hours. It showed an improved performance with respect to other competitive risk scoring systems, including the National EWS (0.653).

Conclusions

We showed that a scoring system incorporating data from a patient’s stay in the ICU has better performance than commonly used EWS systems based on vital signs alone.

Trial registration number

ISRCTN32008295.

Association of antibiotic duration and all-cause mortality in a prospective study of patients with ventilator-associated pneumonia in a tertiary-level critical care unit in Southern India

Por: Stanley · N. D. · Jeevan · J. A. · Yadav · B. · Gunasekaran · K. · Pichamuthu · K. · Chandiraseharan · V. K. · Sathyendra · S. · Hansdak · S. G. · Iyyadurai · R.
Objectives

To estimate all-cause mortality in ventilator-associated pneumonia (VAP) and determine whether antibiotic duration beyond 8 days is associated with reduction in all-cause mortality in patients admitted with VAP in the intensive care unit.

Design

A prospective cohort study of patients diagnosed with VAP based on the National Healthcare Safety Network definition and clinical criteria.

Setting

Single tertiary care hospital in Southern India.

Participants

100 consecutive adult patients diagnosed with VAP were followed up for 28 days postdiagnosis or until discharge.

Outcome measures

The incidence of mortality at 28 days postdiagnosis was measured. Tests for association and predictors of mortality were determined using 2 test and multivariate Cox regression analysis. Secondary outcomes included baseline clinical parameters such as age, underlying comorbidities as well as measuring total length of stay, number of ventilator-free days and antibiotic-free days.

Results

The overall case fatality rate due to VAP was 46%. There was no statistically significant difference in mortality rates between those receiving shorter antibiotic duration (5–8 days) and those on longer therapy. Among those who survived until day 9, the observed risk difference was 15.1% between both groups, with an HR of 1.057 (95% CI 0.26 to 4.28). In 70.4% of isolates, non-fermenting Gram-negative bacilli were identified, of which the most common pathogen isolated was Acinetobacter baumannii (62%).

Conclusion

In this hospital-based cohort study, there is insufficient evidence to suggest that prolonging antibiotic duration beyond 8 days in patients with VAP improves survival.

Using explainable AI to investigate electrocardiogram changes during healthy aging—From expert features to raw signals

by Gabriel Ott, Yannik Schaubelt, Juan Miguel Lopez Alcaraz, Wilhelm Haverkamp, Nils Strodthoff

Cardiovascular diseases remain the leading global cause of mortality. Age is an important covariate whose effect is most easily investigated in a healthy cohort to properly distinguish the former from disease-related changes. Traditionally, most of such insights have been drawn from the analysis of electrocardiogram (ECG) feature changes in individuals as they age. However, these features, while informative, may potentially obscure underlying data relationships. In this paper we present the following contributions: (1) We employ a deep-learning model and a tree-based model to analyze ECG data from a robust dataset of healthy individuals across varying ages in both raw signals and ECG feature format. (2) We use explainable AI methods to identify the most discriminative ECG features across age groups.(3) Our analysis with tree-based classifiers reveals age-related declines in inferred breathing rates and identifies notably high SDANN values as indicative of elderly individuals, distinguishing them from younger adults. (4) Furthermore, the deep-learning model underscores the pivotal role of the P-wave in age predictions across all age groups, suggesting potential changes in the distribution of different P-wave types with age. These findings shed new light on age-related ECG changes, offering insights that transcend traditional feature-based approaches.

Identifying a group of factors predicting cognitive impairment among older adults

by Longgang Zhao, Yuan Wang, Eric Mishio Bawa, Zichun Meng, Jingkai Wei, Sarah Newman-Norlund, Tushar Trivedi, Hatice Hasturk, Roger D. Newman-Norlund, Julius Fridriksson, Anwar T. Merchant

Background

Cognitive impairment has multiple risk factors spanning several domains, but few studies have evaluated risk factor clusters. We aimed to identify naturally occurring clusters of risk factors of poor cognition among middle-aged and older adults and evaluate associations between measures of cognition and these risk factor clusters.

Methods

We used data from the National Health and Nutrition Examination Survey (NHANES) III (training dataset, n = 4074) and the NHANES 2011–2014 (validation dataset, n = 2510). Risk factors were selected based on the literature. We used both traditional logistic models and support vector machine methods to construct a composite score of risk factor clusters. We evaluated associations between the risk score and cognitive performance using the logistic model by estimating odds ratios (OR) and 95% confidence intervals (CI).

Results

Using the training dataset, we developed a composite risk score that predicted undiagnosed cognitive decline based on ten selected predictive risk factors including age, waist circumference, healthy eating index, race, education, income, physical activity, diabetes, hypercholesterolemia, and annual visit to dentist. The risk score was significantly associated with poor cognitive performance both in the training dataset (OR Tertile 3 verse tertile 1 = 8.15, 95% CI: 5.36–12.4) and validation dataset (OR Tertile 3 verse tertile 1 = 4.31, 95% CI: 2.62–7.08). The area under the receiver operating characteristics curve for the predictive model was 0.74 and 0.77 for crude model and model adjusted for age, sex, and race.

Conclusion

The model based on selected risk factors may be used to identify high risk individuals with cognitive impairment.

Specific nanoprobe design for MRI: Targeting laminin in the blood-brain barrier to follow alteration due to neuroinflammation

by Juan F. Zapata-Acevedo, Mónica Losada-Barragán, Johann F. Osma, Juan C. Cruz, Andreas Reiber, Klaus G. Petry, Amael Caillard, Audrey Sauldubois, Daniel Llamosa Pérez, Aníbal José Morillo Zárate, Sonia Bermúdez Muñoz, Agustín Daza Moreno, Rafaela V. Silva, Carmen Infante-Duarte, William Chamorro-Coral, Rodrigo E. González-Reyes, Karina Vargas-Sánchez

Chronic neuroinflammation is characterized by increased blood-brain barrier (BBB) permeability, leading to molecular changes in the central nervous system that can be explored with biomarkers of active neuroinflammatory processes. Magnetic resonance imaging (MRI) has contributed to detecting lesions and permeability of the BBB. Ultra-small superparamagnetic particles of iron oxide (USPIO) are used as contrast agents to improve MRI observations. Therefore, we validate the interaction of peptide-88 with laminin, vectorized on USPIO, to explore BBB molecular alterations occurring during neuroinflammation as a potential tool for use in MRI. The specific labeling of NPS-P88 was verified in endothelial cells (hCMEC/D3) and astrocytes (T98G) under inflammation induced by interleukin 1β (IL-1β) for 3 and 24 hours. IL-1β for 3 hours in hCMEC/D3 cells increased their co-localization with NPS-P88, compared with controls. At 24 hours, no significant differences were observed between groups. In T98G cells, NPS-P88 showed similar nonspecific labeling among treatments. These results indicate that NPS-P88 has a higher affinity towards brain endothelial cells than astrocytes under inflammation. This affinity decreases over time with reduced laminin expression. In vivo results suggest that following a 30-minute post-injection, there is an increased presence of NPS-P88 in the blood and brain, diminishing over time. Lastly, EAE animals displayed a significant accumulation of NPS-P88 in MRI, primarily in the cortex, attributed to inflammation and disruption of the BBB. Altogether, these results revealed NPS-P88 as a biomarker to evaluate changes in the BBB due to neuroinflammation by MRI in biological models targeting laminin.
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