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1.
Trends Neurosci ; 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38824075

RESUMO

Disentangling how cognitive functions emerge from the interplay of brain dynamics and network architecture is among the major challenges that neuroscientists face. Pharmacological and pathological perturbations of consciousness provide a lens to investigate these complex challenges. Here, we review how recent advances about consciousness and the brain's functional organisation have been driven by a common denominator: decomposing brain function into fundamental constituents of time, space, and information. Whereas unconsciousness increases structure-function coupling across scales, psychedelics may decouple brain function from structure. Convergent effects also emerge: anaesthetics, psychedelics, and disorders of consciousness can exhibit similar reconfigurations of the brain's unimodal-transmodal functional axis. Decomposition approaches reveal the potential to translate discoveries across species, with computational modelling providing a path towards mechanistic integration.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38777174

RESUMO

BACKGROUND & AIMS: While upper GI endoscopy (EGD) remains the gold standard for detecting varices in cirrhosis, the Baveno VI criteria proposed a combination of transient elastography and platelet count that could rule out high-risk varices, therefore sparing the need of an endoscopy, with significant potential cost savings. We performed a cost-effectiveness analysis of the Baveno VI criteria compared to EGD in the diagnosis of high-risk varices in cirrhosis. METHODS: We built an analytical decision model to estimate the cost and benefits of using the Baveno VI criteria compared to EGD in patients with Child Pugh A cirrhosis. The analysis was performed from the UK National Health Service (NHS) perspective, over one, five, and 20 years. A Markov model was populated with data from published evidence. Outcomes were measured in terms of Quality Adjusted Life Years (QALYs) and avoided deaths. The analyses were repeated for Canada and Spain, using relevant cost inputs. RESULTS: The Baveno VI criteria were cost-effective compared to endoscopy in all analyses. Over 1000 patients, they produced 0.16 additional QALYs at an incremental cost of £326 ($443.41) over five years, resulting in an incremental cost of £2,081 ($2,830) per additional QALY gained. The Incremental Net Monetary Benefit of Baveno VI compared to EDG was £2,808 ($3,819) over five years per patient. Baveno VI were also cost-effective in Canada and Spain. Deterministic and probabilistic sensitivity analysis supported these findings. CONCLUSION: The findings demonstrate that the Baveno VI criteria are cost-effective, suggesting that they should be considered for widespread implementation on the basis of safety, appropriateness and economic grounds.

3.
Neurorehabil Neural Repair ; : 15459683241252599, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38712875

RESUMO

BACKGROUND: Recent evidence demonstrates that manually triggered vagus nerve stimulation (VNS) combined with rehabilitation leads to increased recovery of upper limb motor function after stroke. This approach is premised on studies demonstrating that the timing of stimulation relative to movements is a key determinant in the effectiveness of this approach. OBJECTIVE: The overall goal of the study was to identify an algorithm that could be used to automatically trigger VNS on the best movements during rehabilitative exercises while maintaining a desired interval between stimulations to reduce the burden of manual stimulation triggering. METHODS: To develop the algorithm, we analyzed movement data collected from patients with a history of neurological injury. We applied 3 different algorithms to the signal, analyzed their triggering choices, and then validated the best algorithm by comparing triggering choices to those selected by a therapist delivering VNS therapy. RESULTS: The dynamic algorithm triggered above the 95th percentile of maximum movement at a rate of 5.09 (interquartile range [IQR] = 0.74) triggers per minute. The periodic algorithm produces stimulation at set intervals but low movement selectivity (34.05%, IQR = 7.47), while the static threshold algorithm produces long interstimulus intervals (27.16 ± 2.01 seconds) with selectivity of 64.49% (IQR = 25.38). On average, the dynamic algorithm selects movements that are 54 ± 3% larger than therapist-selected movements. CONCLUSIONS: This study shows that a dynamic algorithm is an effective strategy to trigger VNS during the best movements at a reliable triggering rate.

4.
J Med Chem ; 67(10): 8077-8098, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38727100

RESUMO

Migration of immune cells to sites of inflammation is a critical step in the body's response to infections but also during autoimmune flares. Chemokine receptors, members of the GPCR receptors, are instrumental in directing specific cell types to their target organs. Herein, we describe a highly potent small molecule antagonist of the chemokine receptor CCR6, which came out of fine-tuned structural elaborations from a proprietary HTS hit. Three main issues in the parent chemical series-cytotoxicity, phototoxicity, and hERG, were successfully solved. Biological characterization demonstrated that compound 45 (IDOR-1117-2520) is a selective and insurmountable antagonist of CCR6. In vivo proof-of-mechanism studies in a mouse lung inflammation model using a representative compound from the chemical class of 45 confirmed that the targeted CCR6+ cells were efficiently inhibited from migrating into the bronchoalveoli. Finally, ADMET and physicochemical properties were well balanced and the preclinical package warranted progress in the clinic.


Assuntos
Doenças Autoimunes , Receptores CCR6 , Receptores CCR6/antagonistas & inibidores , Receptores CCR6/metabolismo , Animais , Humanos , Doenças Autoimunes/tratamento farmacológico , Camundongos , Relação Estrutura-Atividade , Descoberta de Drogas
5.
Otol Neurotol ; 45(5): e435-e442, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38728559

RESUMO

OBJECTIVE: This study evaluates the clinical outcomes of 807 percutaneous wide-diameter bone-anchored hearing implants (BAHIs) in 701 patients. In addition, it compares patient groups and examines bone conduction device (BCD) usage. STUDY DESIGN: Retrospective cohort study. Mean follow-up period of 3.8 years. SETTING: Tertiary referral center. PATIENTS: All patients implanted with a percutaneous wide-diameter BAHI until December 2020 were included. Patients were divided into age groups, "loading-time" groups, and, if applicable, specific subgroups thought to be at risk for complications postsurgery, e.g., intellectual disability and comorbidities. MAIN OUTCOME MEASURES: Soft tissue reaction, implant survival, revision surgery, and BCD usage. RESULTS: In 9.1% of the 5,188 observations of 807 implants, an adverse soft tissue reaction was reported according to the Holgers' scale. Significantly more (adverse) soft tissue reactions were observed in children and intellectually disabled (ID) patients (p < 0.05). Comorbidity subgroups showed no significant differences in soft tissue reactions. Implant loss percentage, including explantations, was 6.2%. Implant survival was significantly worse in patients with ID (14.1%; p = 0.021). Pediatric age, early loading, or comorbidities did not significantly influence implant survival. At least 592 implants (73.4%) were used for bone conduction hearing, of which 65.4% were used daily. CONCLUSION: Both children and ID patients are more prone to (adverse) soft tissue reactions, ID patients only have a higher risk of implant loss. The rate of implant loss in children seemed to be reduced compared to previous studies and thus more comparable to adults since using wide-diameter implants.


Assuntos
Condução Óssea , Prótese Ancorada no Osso , Auxiliares de Audição , Humanos , Masculino , Feminino , Estudos Retrospectivos , Adulto , Criança , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Idoso , Pré-Escolar , Resultado do Tratamento , Reoperação/estatística & dados numéricos , Seguimentos , Idoso de 80 Anos ou mais , Âncoras de Sutura , Complicações Pós-Operatórias/epidemiologia
6.
J Biol Chem ; : 107338, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38705391

RESUMO

Mucosal-associated invariant T (MAIT) cells are a subset of unconventional T cells that recognize small molecule metabolites presented by MHC-I related protein 1 (MR1), via an αß T cell receptor (TCR). MAIT TCRs feature an essentially invariant TCR α-chain, which is highly conserved between mammals. Similarly, MR1 is the most highly conserved MHC-I like molecule. This extreme conservation, including the mode of interaction between the MAIT TCR and MR1, has been shown to allow for species-mismatched reactivities unique in T cell biology thereby allowing the use of selected species-mismatched MR1-antigen (MR1-Ag) tetramers in comparative immunology studies. However, the pattern of cross-reactivity of species-mismatched MR1-Ag tetramers in identifying MAIT cells in diverse species has not been formally assessed. We developed novel cattle and pig MR1-Ag tetramers and utilized these alongside previously developed human, mouse and pig-tailed macaque MR1-Ag tetramers to characterize cross-species tetramer reactivities. MR1-Ag tetramers from each species identified T cell populations in distantly related species with specificity that was comparable to species-matched MR1-Ag tetramers. However, there were subtle differences in staining characteristics with practical implications for the accurate identification of MAIT cells. Pig MR1 is sufficiently conserved across species that pig MR1-Ag tetramers identified MAIT cells from the other species. However, MAIT cells in pigs were at the limits of phenotypic detection. In the absence of sheep MR1-Ag tetramers, a MAIT cell population in sheep blood was identified phenotypically, utilizing species-mismatched MR1-Ag tetramers. Collectively, our results validate the use and limitations of species-mismatched MR1-Ag tetramers in comparative immunology studies.

7.
J Hepatol ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38789011

RESUMO

BACKGROUND: Agile scores, including liver stiffness measurements (LSM) and routine clinical/laboratory biomarkers, have been developed for advanced fibrosis (F≥3) and cirrhosis, respectively, in patients with metabolic-associated steatotic liver disease (MASLD). We independently validated the diagnostic accuracy of these scores in MASLD, alcohol-related liver disease (ALD) and chronic hepatitis B or C (CHB/C) and assessed them in clinical algorithms with FIB-4 and LSM. METHODS: We included 4,243 patients (MASLD:912, ALD:386, CHB:597, CHC:2348) with LSM, liver biopsy and laboratory tests within 6 months. FIB-4, Agile 3+ and Agile 4 scores were calculated. RESULTS: For F≥3, diagnostic accuracy of Agile 3+ and LSM were similar in MASLD (AUC: 0.86 vs 0.86, P=0.831) and ALD (0.92 vs 0.94, P=0.123). For cirrhosis, Agile 4 was similar to LSM in MASLD (0.89 vs 0.90, P=0.412) and ALD (0.94 vs 0.95, P=0.513). Agile 3+/4 performed worse than LSM in CHB/C. Using predefined dual thresholds of 90% Se/Sp, correct classification rates in MASLD were 66% vs 61% using Agile 3+ vs LS dual cut-offs and 71% vs 67% in ALD. When using Agile 3+ or LSM as a second step after FIB-4>1.3, correct classification rates were higher with Agile 3+ than LSM, both for MASLD (75% vs 71%) and for ALD patients (76% vs 72%) with fewer indeterminate results. Positive agreement of LSM and Agile 3+/4 significantly increased the specificity of a diagnosis of advanced fibrosis/cirrhosis. CONCLUSION: Agile 3+ and Agile 4 have equal diagnostic accuracy with LSM in both MASLD and ALD but result in fewer indeterminate results. Sequential use of FIB-4 and Agile 3+/4 or concurrent Agile 3+/4 and LSM can be used to further optimize F≥3 diagnosis.

8.
BMC Health Serv Res ; 24(1): 647, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773589

RESUMO

BACKGROUND: Men who have sex with men (MSM) are at heightened risk for HIV acquisition, yet they may delay or avoid HIV testing due to intersectional stigma experienced at the healthcare facility (HCF). Few validated scales exist to measure intersectional stigma, particularly amongst HCF staff. We developed the Healthcare Facility Staff Intersectional Stigma Scale (HCF-ISS) and assessed factors associated with stigma in Ghana. METHODS: We analyzed baseline data from HCF staff involved in a study testing a multi-level intervention to reduce intersectional stigma experienced by MSM. Data are from eight HCFs in Ghana (HCF Staff n = 200). The HCF-ISS assesses attitudes and beliefs towards same-sex relationships, people living with HIV (PLWH) and gender non-conformity. Exploratory factor analysis assessed HCF-ISS construct validity and Cronbach's alphas assessed the reliability of the scale. Multivariable regression analyses assessed factors associated with intersectional stigma. RESULTS: Factor analysis suggested an 18-item 3-factor scale including: Comfort with Intersectional Identities in the Workplace (6 items, Cronbach's alpha = 0.71); Beliefs about Gender and Sexuality Norms (7 items, Cronbach's alpha = 0.72); and Beliefs about PLWH (5 items, Cronbach's alpha = 0.68). Having recent clients who engage in same-gender sex was associated with greater comfort with intersectional identities but more stigmatizing beliefs about PLWH. Greater religiosity was associated with stigmatizing beliefs. Infection control training was associated with less stigma towards PLWH and greater comfort with intersectional identities. CONCLUSIONS: Achieving the goal of ending AIDS by 2030 requires eliminating barriers that undermine access to HIV prevention and treatment for MSM, including HCF intersectional stigma. The HCF-ISS provides a measurement tool to support intersectional stigma-reduction interventions.


Assuntos
Infecções por HIV , Pessoal de Saúde , Estigma Social , Humanos , Gana , Masculino , Infecções por HIV/psicologia , Adulto , Pessoal de Saúde/psicologia , Feminino , Homossexualidade Masculina/psicologia , Inquéritos e Questionários , Atitude do Pessoal de Saúde , Reprodutibilidade dos Testes , Pessoa de Meia-Idade , Análise Fatorial , Minorias Sexuais e de Gênero/psicologia
9.
Artigo em Inglês | MEDLINE | ID: mdl-38767799

RESUMO

Conventional drugs have been facing various drug delivery obstacles, including first-pass metabolism for oral medications, drug degradation by cellular enzymes, off-target effects, and cytotoxicity of healthy cells. Nanoparticles (NP) application in drug delivery can compensate for these drawbacks to a great extent. NPs can be fabricated using different materials and structures to achieve desired therapeutic effects. For each type of NP material, its physicochemical properties determine compatibility with specific drugs and other supplemental compositions. The optimized material selection becomes prominent in NP development to improve NP performances. Due to the nature of NP fabrication, the process is long and expensive. To accelerate NP composition optimization, machine learning (ML) techniques are among the most promising methods for efficient data predictions and optimizations.As a proof-of concept, we created Gaussian Process (GP) models to make predictions for drug encapsulation efficiency (EE%) and therapeutic efficacy of 32 poly (lactic-co-glycolic acid) (PLGA) NPs that are formed with materials with different physicochemical properties. Two model drugs, doxorubicin (DOX) and docetaxel (DTX) were loaded separately. The IC50 values for the various NPs formulations were evaluated using the OVCAR3 epithelial ovarian cancer cell line. EE% GP model has the highest prediction accuracy with the lowest normalized root-mean-squared-error (RMSE) of 0.187. The DOX and DTX IC50 GP models have normalized RMSEs of 0.296 and 0.206, respectively, which are higher than that of the EE% GP model.

11.
Brain Behav Immun Health ; 38: 100779, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38725444

RESUMO

Introduction: Generalized anxiety disorder (GAD) has been associated with elevated levels of C-reactive protein (CRP) and proinflammatory cytokines. Despite robust evidence as an effective treatment for GAD, research on the effects of cognitive-behavioral therapies (CBT) in the inflammatory profile of patients with clinical anxiety has presented mixed results. Objective: The present study aimed to investigate the effect of an acceptance-based behavior therapy (ABBT) on inflammatory biomarkers and their association with anxiety levels in GAD patients in comparison to supportive therapy as an active control. Methods: Peripheral inflammatory biomarkers (CRP, IL-1ß, IL-4, IL-6, IL-10, TNF-α) were measured in 77 GAD patients who participated in a 14-week 10-session randomized clinical trial of group ABBT (experimental, n = 37) or supportive group therapy (ST: active control group, n = 40). Results: The concentrations of IL-1ß decreased in the control group and the concentrations of IL-6 increased in the experimental group from baseline to post-treatment, whereas no difference was identified in IL-4, IL-10, TNF, or CRP. Although anxiety and depression levels decreased in both treatment conditions, no correlation with inflammation markers was found for most clinical and biological variables. A negative correlation between changes in IL-6 and IL-10 and anxiety symptom score changes was identified. Conclusions: The present study results found that a short trial of acceptance-based behavior therapy did not change the proinflammatory profile which may be associated with GAD. Additional research is needed to evaluate the influence of other inflammation-related variables, longer periods of follow-up as well as the effect of supportive therapy on peripheral inflammatory biomarkers in GAD patients.

12.
Sci Rep ; 14(1): 12024, 2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38797811

RESUMO

Perovskite solar cells (PSCs) have gained much attention in recent years because of their improved energy conversion efficiency, simple fabrication process, low processing temperature, flexibility, light weight, and low cost of constituent materials when compared with their counterpart silicon based solar cells. Besides, stability and toxicity of PSCs and low power conversion efficiency have been an obstacle towards commercialization of PSCs which has attracted intense research attention. In this research paper, a Glass/Cu2O/CH3NH3SnI3/ZnO/Al inverted device structure which is made of cheap inorganic materials, n-type transparent conducting oxide (TCO)-free, stable, photoexcited toxic-free perovskite have been carefully designed, simulated and optimized using a one-dimensional solar cell capacitance simulator (SCAPS-1D) software. The effects of layers' thickness, perovskite's doping concentration and back contact electrodes have been investigated, and the optimized structure produced an open circuit voltage (Voc) of 1.0867 V, short circuit current density (JSC) of 33.4942 mA/cm2, fill factor (FF) of 82.88% and power conversion efficiency (PCE) of 30.17%. This paper presents a model that is first of its kind where the highest PCE performance and eco-friendly n-type TCO-free inverted CH3NH3SnI3 based perovskite solar cell is achieved using all-inorganic transport materials.

13.
JAC Antimicrob Resist ; 6(3): dlae081, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38803386

RESUMO

Background: Antimicrobial resistance (AMR) is a growing public health concern globally, and misuse of antibiotics is a major contributor. Objective: This study investigated antibiotic utilization patterns before and during the COVID-19 pandemic in Tanzania using data from the Tanzania Medicines and Medical Devices Authority (TMDA). Methods: This retrospective longitudinal study analysed secondary data. The study compared antibiotics consumption in defined daily doses per 1000 inhabitants per day (DID) in two distinct eras: 2018-2019 as the pre-COVID-19 era and 2020-2021 as the intra-COVID-19 era. A sample t-test was conducted using Statistical Package for the Social Sciences. Results: The study analysed 10 614 records and found an overall increase in antibiotics consumption from 2018 to 2021. We found that the consumption was 61.24 DID in the intra-COVID-19 era and 50.32 DID in the pre-COVID-19 era. Levofloxacin had the highest percentage increase in use, with a 700% increase in DID during the intra-COVID-19 era. Azithromycin had a 163.79% increase, while cefotaxime had a 600% increase. By contrast, some antibiotics exhibited a decrease in usage during the intra-COVID-19 era, such as nalidixic acid, which had a 100% decrease, and cefpodoxime, which had a 66.67% decrease. Conclusions: Increased antibiotic consumption during the COVID-19 pandemic highlights the importance of implementing effective antimicrobial stewardship strategies to prevent AMR, especially during pandemics.

14.
J Phys Chem B ; 128(16): 3946-3952, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38624216

RESUMO

The microviscosity of intracellular environments plays an important role in monitoring cellular function. Thus, the capability of detecting changes in viscosity can be utilized for the detection of different disease states. Viscosity-sensitive fluorescent molecular rotors are potentially excellent probes for these applications; however, the predictable relationships between chemical structural features and viscosity sensitivity are poorly understood. Here, we investigate a set of arylcyanoamide-based fluorescent probes and the effect of small aliphatic substituents on their viscosity sensitivity. We found that the location of the substituents and the type of π-network of the fluorophore can significantly affect the viscosity sensitivity of these fluorophores. Computational analysis supported the notion that the excited state rotational energy barrier plays a dominant role in the relative viscosity sensitivity of these fluorophores. These findings provide valuable insight into the design of molecular rotor-based fluorophores for viscosity measurement.

15.
Cureus ; 16(2): e55172, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38558682

RESUMO

This case report presents the clinical details of a 42-year-old female without previous medical issues who presented with upper gastrointestinal bleeding (UGIB) characterized by melanotic stools. Initial examination revealed mild anemia and subsequent endoscopy identified a 4 cm submucosal gastric mass displaying recent bleeding indicators. Subsequent surgical pathology confirmed a high-grade gastrointestinal stromal tumor (GIST) of grade 2 with a heightened risk of recurrence. The significance of this case lies in underscoring the necessity of considering GIST in the differential diagnosis of UGIB, particularly among middle-aged individuals with no identifiable risk factors such as recent or chronic non-steroidal anti-inflammatory drug (NSAID) use, peptic ulcer disease, or alarm symptoms. Early detection and prompt surgical intervention assume paramount importance in enhancing patient outcomes. While complete resection stands as the cornerstone of treatment, adjuvant imatinib therapy is recommended for high-risk patients to mitigate the risk of recurrence.

16.
J Pharm Pharm Sci ; 27: 12797, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38558867

RESUMO

Additive manufacturing, commonly referred to as three-dimensional (3D) printing, has the potential to initiate a paradigm shift in the field of medicine and drug delivery. Ever since the advent of the first-ever United States Food and Drug Administration (US FDA)-approved 3D printed tablet, there has been an increased interest in the application of this technology in drug delivery and biomedical applications. 3D printing brings us one step closer to personalized medicine, hence rendering the "one size fits all" concept in drug dosing obsolete. In this review article, we focus on the recent developments in the field of modified drug delivery systems in which various types of additive manufacturing technologies are applied.


Assuntos
Produtos Biológicos , Tecnologia Farmacêutica , Estados Unidos , Tecnologia Farmacêutica/métodos , Impressão Tridimensional , Sistemas de Liberação de Medicamentos , Comprimidos
17.
J West Afr Coll Surg ; 14(2): 218-224, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38562394

RESUMO

Introduction: This study aimed at determining the predictive value (PV) of transrectal ultrasonic Doppler and elastographic features in prostate cancer (PCa) detection among patients in Lagos University Teaching Hospital. Materials and Methods: This prospective study involved patients that underwent evaluation for PCa. Participants had digital rectal examination (DRE), prostate-specific antigen (PSA) assay, and transrectal ultrasound-guided prostate biopsy using colour Doppler (CD) and elastography. All cores were sent for histopathology. Data were analysed using Statistical Package for the Social Sciences Version 22.0. CD and elastography PV in PCa detection and their relationships to the Gleason score (GS) were analysed (P < 0.05). Results: Seventy men (aged between 45 and 87 years) were enrolled. Forty-three (61.4%) patients had PCa with a mean age of 69.37 ± 8.22years. The sensitivity, specificity, positive PV (PPV), negative PV (NPV) and accuracy of CD were 8.50%, 97.44%, 64.10%, 66.42% and 66.31%, respectively. The sensitivity, specificity, PPV, NPV and accuracy of elastography were 84.21%, 94.59%, 88.89%, 92.11% and 91.07%, respectively. Conclusion: There is a significant association between decreased elasticity (elastography) and PCa detection but a weak association between increased vascularity (CD) and PCa detection. A positive correlation exists between extent of prostatic stiffness and GS.

18.
Int Urol Nephrol ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38557818

RESUMO

BACKGROUND: The interplay between serum bicarbonate levels and kidney outcomes is not fully understood. We conducted a prospective cohort study in three intensive care units (ICUs) to evaluate the association of serum bicarbonate levels with acute kidney injury (AKI) and kidney function recovery in critically ill patients. METHODS: A prospective cohort study in three intensive care units (ICUs) was performed. The serum bicarbonate level in the first 24 h after ICU admission was categorized as low (< 22 mEq/L), normal (22-26 mEq/L), or high (> 26 mEq/L). Serum creatinine (SCr) levels according to the KDIGO AKI guideline were used for defining AKI within the first 7 days of ICU stay. At ICU admission, SCr ≥ 1.1 for women and ≥ 1.3 mg/dL for men were indicative of impaired kidney function. Mortality outcome was tracked up to 28 days, and kidney function recovery was assessed at hospital discharge. RESULTS: A total of 2732 patients (66 ± 19 years and 55% men) were analyzed, with 32% having impaired kidney function at ICU admission. Overall, 26% of patients had low bicarbonate levels, while 32% had high bicarbonate levels. Notably, patients with preserved kidney function showed a lower prevalence of low bicarbonate levels compared to those with impaired kidney function (20% vs. 39%, p < 0.001), while higher rates were observed for high bicarbonate (35% vs. 24%, p < 0.001). Compared with patients with normal serum bicarbonate levels, those with low bicarbonate were 81% more likely to develop AKI (OR = 1.81; 95% CI 1.10-2.99), whereas those with high bicarbonate were 44% less likely (OR = 0.56; 95% CI 0.32-0.98) in the adjusted model for confounders. Neither those with high nor low serum bicarbonate levels were associated with an increased risk of mortality (HR = 1.03; 95% CI 0.68-1.56 and 0.99; 95% CI 0.68-1.42, respectively). In subgroup analysis, regardless of the kidney function at ICU admission, serum bicarbonate levels were not associated with the development of AKI and all-cause mortality. Regarding kidney function recovery, higher non-recovery rates were found for those with low bicarbonate. CONCLUSION: In critically ill ICU patients, low bicarbonate levels were associated with the more likely development of AKI and subsequent non-recovery of kidney function, while high bicarbonate levels showed no such association. Therefore, low bicarbonate levels may be considered a risk factor for adverse kidney outcomes in critically ill patients.

19.
BMC Infect Dis ; 24(1): 390, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605325

RESUMO

BACKGROUND: The world is moving towards the third target of the Joint United Nations Programme on HIV/AIDS to ensure most people receiving antiretroviral therapy (ART) are virologically suppressed. Little is known about viral suppression at an undetectable level and the risk of viral rebound phenomenon in sub-Saharan Africa which covers 67% of the global HIV burden.This study aimed to investigate the proportion of viral suppression at an undetectable level and the risk of viral rebound among people living with HIV receiving ART in northern Tanzania. METHODOLOGY: A hospital based-retrospective study recruited people living with HIV who were on ART for at least two years at Kibong'oto Infectious Disease Hospital and Mawenzi Regional Referral Hospital in Kilimanjaro Region, Tanzania. Participants' two-year plasma HIV were captured at months 6, 12, and 24 of ART. Undetectable viral load was defined by plasma HIV of viral load (VL) less than 20copies/ml and viral rebound (VR) was considered to anyone having VL of more than 50 copies/ml after having history of undetectable level of the VL less than 20copies/ml. A multivariable log-binomial generalized linear model was used to determine factors for undetectable VL and viral VR. RESULTS: Among 416 PLHIV recruited, 226 (54.3%) were female. The mean (standard deviation) age was 43.7 (13.3) years. The overall proportion of undetectable VL was 68% (95% CI: 63.3-72.3) and 40.0% had viral rebound (95% CI: 34.7-45.6). Participants who had at least 3 clinic visits were 1.3 times more likely to have undetectable VL compared to those who had 1 to 2 clinic visits in a year (p = 0.029). Similarly, participants with many clinical visits ( > = 3 visits) per year were less likely to have VR compared to those with fewer visits ( = 2 visits) [adjusted relative risk (aRR) = 0.64; 95% CI: 0.44-0.93]. CONCLUSION: Participants who had fewer clinic visits per year(ART refills) were less likely to achieve viral suppression and more likely to experience viral rebound. Enhanced health education and close follow-up of PLHIV on antiretroviral therapy are crucial to reinforce adherence and maintain an undetectable viral load.


Assuntos
Síndrome da Imunodeficiência Adquirida , Fármacos Anti-HIV , Infecções por HIV , Humanos , Feminino , Adulto , Masculino , Estudos Retrospectivos , Terapia Antirretroviral de Alta Atividade , Tanzânia/epidemiologia , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Carga Viral , Fármacos Anti-HIV/uso terapêutico
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