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1.
Chem Soc Rev ; 53(7): 3273-3301, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38507263

RESUMO

Oral diseases are prevalent but challenging diseases owing to the highly movable and wet, microbial and inflammatory environment. Polymeric materials are regarded as one of the most promising biomaterials due to their good compatibility, facile preparation, and flexible design to obtain multifunctionality. Therefore, a variety of strategies have been employed to develop materials with improved therapeutic efficacy by overcoming physicobiological barriers in oral diseases. In this review, we summarize the design strategies of polymeric biomaterials for the treatment of oral diseases. First, we present the unique oral environment including highly movable and wet, microbial and inflammatory environment, which hinders the effective treatment of oral diseases. Second, a series of strategies for designing polymeric materials towards such a unique oral environment are highlighted. For example, multifunctional polymeric materials are armed with wet-adhesive, antimicrobial, and anti-inflammatory functions through advanced chemistry and nanotechnology to effectively treat oral diseases. These are achieved by designing wet-adhesive polymers modified with hydroxy, amine, quinone, and aldehyde groups to provide strong wet-adhesion through hydrogen and covalent bonding, and electrostatic and hydrophobic interactions, by developing antimicrobial polymers including cationic polymers, antimicrobial peptides, and antibiotic-conjugated polymers, and by synthesizing anti-inflammatory polymers with phenolic hydroxy and cysteine groups that function as immunomodulators and electron donors to reactive oxygen species to reduce inflammation. Third, various delivery systems with strong wet-adhesion and enhanced mucosa and biofilm penetration capabilities, such as nanoparticles, hydrogels, patches, and microneedles, are constructed for delivery of antibiotics, immunomodulators, and antioxidants to achieve therapeutic efficacy. Finally, we provide insights into challenges and future development of polymeric materials for oral diseases with promise for clinical translation.


Assuntos
Anti-Infecciosos , Polímeros , Polímeros/química , Materiais Biocompatíveis/química , Anti-Inflamatórios , Fatores Imunológicos
2.
Eur J Med Res ; 28(1): 425, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37821966

RESUMO

Current research has described improving multisystem disease and organ function through dietary nitrate (DN) supplementation. They have provided some evidence that these floras with nitrate (NO3-) reductase are mediators of the underlying mechanism. Symbiotic bacteria with nitrate reductase activity (NRA) are found in the human digestive tract, including the mouth, esophagus and gastrointestinal tract (GT). Nitrate in food can be converted to nitrite under the tongue or in the stomach by these symbiotic bacteria. Then, nitrite is transformed to nitric oxide (NO) by non-enzymatic synthesis. NO is currently recognized as a potent bioactive agent with biological activities, such as vasodilation, regulation of cardiomyocyte function, neurotransmission, suppression of platelet agglutination, and prevention of vascular smooth muscle cell proliferation. NO also can be produced through the conventional L-arginine-NO synthase (L-NOS) pathway, whereas endogenous NO production by L-arginine is inhibited under hypoxia-ischemia or disease conditions. In contrast, exogenous NO3-/NO2-/NO activity is enhanced and becomes a practical supplemental pathway for NO in the body, playing an essential role in various physiological activities. Moreover, many diseases (such as metabolic or geriatric diseases) are primarily associated with disorders of endogenous NO synthesis, and NO generation from the exogenous NO3-/NO2-/NO route can partially alleviate the disease progression. The imbalance of NO in the body may be one of the potential mechanisms of disease development. Therefore, the impact of these floras with nitrate reductase on host systemic health through exogenous NO3-/NO2-/NO pathway production of NO or direct regulation of floras ecological balance is essential (e.g., regulation of body homeostasis, amelioration of diseases, etc.). This review summarizes the bacteria with nitrate reductase in humans, emphasizing the relationship between the metabolic processes of this microflora and host systemic health and disease. The potential effects of nitrate reduction bacteria on human health and disease were also highlighted in disease models from different human systems, including digestive, cardiovascular, endocrine, nervous, respiratory, and urinary systems, providing innovative ideas for future disease diagnosis and treatment based on nitrate reduction bacteria.


Assuntos
Nitratos , Nitritos , Humanos , Idoso , Nitratos/farmacologia , Nitratos/metabolismo , Nitritos/metabolismo , Óxido Nítrico/metabolismo , Dióxido de Nitrogênio/metabolismo , Bactérias/metabolismo , Nitrato Redutases/metabolismo , Arginina/metabolismo
3.
Acta Biomater ; 172: 38-52, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37816417

RESUMO

External pathogenic microorganisms and commensal microorganisms in the body have either harmful or beneficial impacts on the regenerative repair of tissues, and the immune system plays a crucial regulatory role in this process. This review summarises our current understanding of microorganism-immune system interactions, with a focus on how these interactions impact the renewal and repair ability of tissues, including skin, bone, gut, liver, and nerves. This review concludes with a discussion of the mechanisms by which microbes act on various types of immune cells to affect tissue regeneration, offers potential strategies for using microbial therapies to enhance the regenerative repair function of tissues, and suggest novel therapeutic approaches for regenerative medicine. STATEMENT OF SIGNIFICANCE: Microbiological communities have crucial impacts on human health and illness by participating in energy collection and storage and performing various metabolic processes. External pathogenic microorganisms and commensal microorganisms in the body have either harmful or beneficial impacts on the regenerative repair of tissues, and the immune system plays a critical regulatory role in this process. This study reviews the important correlation between microorganisms and the immune system and investigates the mechanism of various microorganism that participate in the regeneration and repair of tissues and organs by modulating immune system.


Assuntos
Imunidade , Cicatrização , Humanos , Medicina Regenerativa , Sistema Imunitário , Pele
4.
BioDrugs ; 37(3): 331-352, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37178431

RESUMO

Type 1 diabetes mellitus (T1DM) has been defined as an autoimmune disease characterised by immune-mediated destruction of the pancreatic ß cells, leading to absolute insulin deficiency and hyperglycaemia. Current research has increasingly focused on immunotherapy based on immunosuppression and regulation to rescue T-cell-mediated ß-cell destruction. Although T1DM immunotherapeutic drugs are constantly under clinical and preclinical development, several key challenges remain, including low response rates and difficulty in maintaining therapeutic effects. Advanced drug delivery strategies can effectively harness immunotherapies and improve their potency while reducing their adverse effects. In this review, we briefly introduce the mechanisms of T1DM immunotherapy and focus on the current research status of the integration of the delivery techniques in T1DM immunotherapy. Furthermore, we critically analyse the challenges and future directions of T1DM immunotherapy.


Assuntos
Diabetes Mellitus Tipo 1 , Humanos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Imunoterapia/métodos , Insulina/uso terapêutico , Linfócitos T
5.
Biomater Sci ; 11(12): 4151-4183, 2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37161951

RESUMO

The influence of metal and metal oxide nanomaterials on various fields since their discovery has been remarkable. They have unique properties, and therefore, have been employed in specific applications, including biomedicine. However, their potential health risks cannot be ignored. Several studies have shown that exposure to metal and metal oxide nanoparticles can lead to immunotoxicity. Different types of metals and metal oxide nanoparticles may have a negative impact on the immune system through various mechanisms, such as inflammation, oxidative stress, autophagy, and apoptosis. As an essential factor in determining the function and fate of immune cells, immunometabolism may also be an essential target for these nanoparticles to exert immunotoxic effects in vivo. In addition, the biodegradation and metabolic outcomes of metal and metal oxide nanoparticles are also important considerations in assessing their immunotoxic effects. Herein, we focus on the cellular mechanism of the immunotoxic effects and toxic effects of different types of metal and metal oxide nanoparticles, as well as the metabolism and outcomes of these nanoparticles in vivo. Also, we discuss the relationship between the possible regulatory effect of nanoparticles on immunometabolism and their immunotoxic effects. Finally, we present perspectives on the future research and development direction of metal and metal oxide nanomaterials to promote scientific research on the health risks of nanomaterials and reduce their adverse effects on human health.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Humanos , Óxidos/toxicidade , Nanopartículas/toxicidade , Nanopartículas Metálicas/toxicidade , Sistema Imunitário , Metais/toxicidade , Estresse Oxidativo
6.
Macromol Rapid Commun ; 44(15): e2300128, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37139707

RESUMO

Regenerative medicine is a highly regarded multidisciplinary field that aims to transform the future of clinical medicine through curative strategies rather than palliative therapies. As an emerging field, the development of regenerative medicine cannot be achieved without multifunctional biomaterials. Among the various bioscaffold materials, hydrogels are one of the materials of interest in bioengineering and medical research because of their similarity to the natural extracellular matrix and good biocompatibility. However, conventional hydrogels have simple internal structures and single cross-linking modes, which require improvement in a single function and structural stability. Introducing multifunctional nanomaterials into 3D hydrogel networks physically or chemically avoids their disadvantages. Nanomaterials (NMs) are materials in the size range of 1-100 nm with distinct physical and chemical properties that differ from that of the macroscopic size and enable hydrogels to exhibit multifunctionality. Although regenerative medicine and hydrogels have been well researched in their respective fields, the connection between nanocomposite hydrogels (NCHs) and regenerative medicine has not been elaborated. Therefore, this review briefly describes the preparation and design requirements of NCHs and discusses their applications and challenges in regenerative medicine, hoping to clarify the relationship between the two.


Assuntos
Medicina Regenerativa , Engenharia Tecidual , Nanogéis , Materiais Biocompatíveis/uso terapêutico , Hidrogéis/química
7.
Arch Oral Biol ; 151: 105695, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37086493

RESUMO

OBJECTIVE: To study the effect of FAM72 on the prognosis of patients with oral squamous cell carcinoma (OSCC) and to explore the relationship between FAM72 and OSCC. DESIGN: We used a vast array of databases and analytical vehicles to assess the relation between FAM72 and OSCC, including The Cancer Genome Atlas (TCGA), Metascape, and MethSurv. We made a preliminary verification of OSCC lines and tissues by real time quantitative polymerase chain reaction (RT-qPCR). RESULTS: FAM72 was higher in OSCC than in normal tissues. Analysis of univariate COX data indicated that elevated expression of FAM72A, FAM72B, and FAM72C in OSCC was related to poor overall survival. Moreover, FAM72B and FAM72C were independent of overall survival in multiple COX regression. FAM72A-D and its coexpressed genes in Metascape were analyzed by Gene Ontology (GO), they were enriched in cellular cycle, mitotic and DNA metabolism. Gene set enrichment analysis (GSEA) demonstrated an enrichment in pathways related to cell metabolism. Additionally, high FAM72 expression related to a worse prognosis in OSCC patients. FAM72A-D linked to the infiltration of tumor immune cell in OSCC patients. We found that methylation levels are likely linked to prognosis in OSCC patients. We used RT-qPCR to ascertain the differential FAM72B and FAM72C expression levels in cancer and paracancerous tissues of OSCC, human normal oral keratinocytes (HOK), and human tongue squamous cell carcinoma (Cal-33). CONCLUSION: Our findings indicate that FAM72B and FAM72C are potential molecular markers of poor prognosis in OSCC and may act as novel targets for OSCC treatment strategies.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Neoplasias da Língua , Humanos , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Neoplasias Bucais/patologia , Neoplasias da Língua/genética , Prognóstico , Biomarcadores Tumorais/genética , Neoplasias de Cabeça e Pescoço/genética , Regulação Neoplásica da Expressão Gênica
8.
Clin Chem Lab Med ; 61(1): 4-32, 2023 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-36285724

RESUMO

Saliva is a complex biological fluid with a variety of biomolecules, such as DNA, RNA, proteins, metabolites and microbiota, which can be used for the screening and diagnosis of many diseases. In addition, saliva has the characteristics of simple collection, non-invasive and convenient storage, which gives it the potential to replace blood as a new main body of fluid biopsy, and it is an excellent biological diagnostic fluid. This review integrates recent studies and summarizes the research contents of salivaomics and the research progress of saliva in early diagnosis of oral and systemic diseases. This review aims to explore the value and prospect of saliva diagnosis in clinical application.


Assuntos
Microbiota , Saliva , Humanos , Saliva/química , Biomarcadores/análise , Diagnóstico Precoce , Biópsia
9.
Front Cell Infect Microbiol ; 12: 974259, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36467727

RESUMO

Severe burn is a serious acute trauma that can lead to significant complications such as sepsis, multiple organ failure, and high mortality worldwide. The gut microbiome, the largest microbial reservoir in the human body, plays a significant role in this pathogenic process. Intestinal dysbiosis and disruption of the intestinal mucosal barrier are common after severe burn, leading to bacterial translocation to the bloodstream and other organs of the body, which is associated with many subsequent severe complications. The progression of some intestinal diseases can be improved by modulating the composition of gut microbiota and the levels of its metabolites, which also provides a promising direction for post-burn treatment. In this article, we summarised the studies describing changes in the gut microbiome after severe burn, as well as changes in the function of the intestinal mucosal barrier. Additionally, we presented the potential and challenges of microbial therapy, which may provide microbial therapy strategies for severe burn.


Assuntos
Microbioma Gastrointestinal , Sepse , Humanos , Translocação Bacteriana , Mucosa Intestinal , Sepse/terapia
10.
Biomater Sci ; 10(22): 6413-6446, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36069391

RESUMO

Oral and maxillofacial diseases such as infection and trauma often involve various organs and tissues, resulting in structural defects, dysfunctions and/or adverse effects on facial appearance. Hydrogels have been applied in the treatment of oral diseases and defect repair due to their three-dimensional network structure. With their biocompatible structure and unique stimulus-responsive property, hydrogels have been applied as an excellent drug-delivery system for treatments that mainly include oral mucosal diseases, wounds, periodontitis and cancer therapy. Hydrogels are also ideal scaffolds in regenerative engineering of dentin-pulp complex, periodontal tissue, bone and cartilage. This review discusses the fundamental structure of hydrogels in brief and then focuses on the characteristics and limitations in current research and applications of hydrogels. Finally, potential future directions are proposed.


Assuntos
Hidrogéis , Engenharia Tecidual , Hidrogéis/química , Engenharia Tecidual/métodos , Cartilagem , Osso e Ossos , Sistemas de Liberação de Medicamentos , Alicerces Teciduais/química , Materiais Biocompatíveis/química
11.
Int J Nanomedicine ; 17: 2679-2705, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35733418

RESUMO

Oral cancer is one of the most common cancers in the world, with more than 300,000 cases diagnosed each year, of which oral squamous cell carcinoma accounts for more than 90%, with a 5-year survival rate of only 40-60%, and poor prognosis. Exploring new strategies for the early diagnosis and treatment of oral cancer is key to improving the survival rate. Exosomes are nanoscale lipid bilayer membrane vesicles that are secreted by almost all cell types. During the development of oral cancer, exosomes can transport their contents (DNA, RNA, proteins, etc) to target cells and promote or inhibit the proliferation, invasion, and metastasis of oral cancer cells by influencing the host immune response, drug-resistant metastasis, and tumour angiogenesis. Therefore, exosomes have great potential and advantages as biomarkers for oral cancer diagnosis, and as drug delivery vehicles or targets for oral cancer therapy. In this review, we first describe the biogenesis, biological functions, and isolation methods of exosomes, followed by their relationship with oral cancer. Here, we focused on the potential of exosomes as oral cancer biomarkers, drug carriers, and therapeutic targets. Finally, we provide an insightful discussion of the opportunities and challenges of exosome application in oral cancer diagnosis and treatment, intending to offer new ideas for the clinical management of oral cancer.


Assuntos
Carcinoma de Células Escamosas , Exossomos , Neoplasias Bucais , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Exossomos/metabolismo , Humanos , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/terapia
12.
Front Cell Infect Microbiol ; 12: 815318, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35186795

RESUMO

Fusobacterium nucleatum is a common oral opportunistic bacterium that can cause different infections. In recent years, studies have shown that F. nucleatum is enriched in lesions in periodontal diseases, halitosis, dental pulp infection, oral cancer, and systemic diseases. Hence, it can promote the development and/or progression of these conditions. The current study aimed to assess research progress in the epidemiological evidence, possible pathogenic mechanisms, and treatment methods of F. nucleatum in oral and systemic diseases. Novel viewpoints obtained in recent studies can provide knowledge about the role of F. nucleatum in hosts and a basis for identifying new methods for the diagnosis and treatment of F. nucleatum-related diseases.


Assuntos
Infecções por Fusobacterium , Neoplasias Bucais , Doenças Periodontais , Infecções por Fusobacterium/diagnóstico , Infecções por Fusobacterium/microbiologia , Fusobacterium nucleatum , Humanos
13.
Front Cell Dev Biol ; 9: 740574, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34869324

RESUMO

Traditional cell lines and xenograft models have been widely recognized and used in research. As a new research model, organoids have made significant progress and development in the past 10 years. Compared with traditional models, organoids have more advantages and have been applied in cancer research, genetic diseases, infectious diseases, and regenerative medicine. This review presented the advantages and disadvantages of organoids in physiological development, pathological mechanism, drug screening, and organ transplantation. Further, this review summarized the current situation of vascularization, immune microenvironment, and hydrogel, which are the main influencing factors of organoids, and pointed out the future directions of development.

14.
Front Cell Dev Biol ; 9: 765859, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34912804

RESUMO

Regulatory cell death has been a major focus area of cancer therapy research to improve conventional clinical cancer treatment (e.g. chemotherapy and radiotherapy). Ferroptosis, a novel form of regulated cell death mediated by iron-dependent lipid peroxidation, has been receiving increasing attention since its discovery in 2012. Owing to the highly iron-dependent physiological properties of cancer cells, targeting ferroptosis is a promising approach in cancer therapy. In this review, we summarised the characteristics of ferroptotic cells, associated mechanisms of ferroptosis occurrence and regulation and application of the ferroptotic pathway in cancer therapy, including the use of ferroptosis in combination with other therapeutic modalities. In addition, we presented the challenges of using ferroptosis in cancer therapy and future perspectives that may provide a basis for further research.

15.
Front Oncol ; 11: 770241, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35127477

RESUMO

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is still a menace to public wellbeing globally. However, the underlying molecular events influencing the carcinogenesis and prognosis of HNSCC are poorly known. METHODS: Gene expression profiles of The Cancer Genome Atlas (TCGA) HNSCC dataset and GSE37991 were downloaded from the TCGA database and gene expression omnibus, respectively. The common differentially expressed metabolic enzymes (DEMEs) between HNSCC tissues and normal controls were screened out. Then a DEME-based molecular signature and a clinically practical nomogram model were constructed and validated. RESULTS: A total of 23 commonly upregulated and 9 commonly downregulated DEMEs were identified in TCGA HNSCC and GSE37991. Gene ontology analyses of the common DEMEs revealed that alpha-amino acid metabolic process, glycosyl compound metabolic process, and cellular amino acid metabolic process were enriched. Based on the TCGA HNSCC cohort, we have built up a robust DEME-based prognostic signature including HPRT1, PLOD2, ASNS, TXNRD1, CYP27B1, and FUT6 for predicting the clinical outcome of HNSCC. Furthermore, this prognosis signature was successfully validated in another independent cohort GSE65858. Moreover, a potent prognostic signature-based nomogram model was constructed to provide personalized therapeutic guidance for treating HNSCC. In vitro experiment revealed that the knockdown of TXNRD1 suppressed malignant activities of HNSCC cells. CONCLUSION: Our study has successfully developed a robust DEME-based signature for predicting the prognosis of HNSCC. Moreover, the nomogram model might provide useful guidance for the precision treatment of HNSCC.

16.
J Acquir Immune Defic Syndr ; 83(4): 424-433, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31904706

RESUMO

BACKGROUND: Adolescents and young adults (AYA) with HIV experience poorer health outcomes compared with adults. To improve care for AYA with HIV, information about patterns of costly health care resource utilization is needed. METHODS: Among 13-30 year olds in the US HIV Research Network, we stratified outpatient visits, emergency department (ED) visits, and inpatient days/person-year (PY) by HIV acquisition model [perinatal (PHIVY) and nonperinatal (NPHIVY)], age (13-17, 18-23, and 24-30 years), CD4 strata (<200, 200-499, and ≥500 cells/µL), and viral load (VL) suppression (<, ≥400 copies/mL [c/mL]) combined with antiretroviral (ARV) use. RESULTS: Among 4540 AYA (PHIVY: 15%; NPHIVY: 85%), mean follow-up was 2.8 years. Among PHIVY, most person-time (PT) was spent between ages 13 and 23 years (13-17 years: 43%; 18-23 years: 45%), CD4 ≥500/µL (61%), and VL <400 c/mL (69%). Among NPHIVY, most PT was spent between ages 24 and 30 years (56%), with CD4 ≥500/µL (54%), and with VL <400 c/mL (67%). PT spent while prescribed ARVs and with VL ≥400 c/mL was 29% (PHIVY) and 24% (NPHIVY). For PHIVY and NPHIVY, outpatient visit rates were higher at younger ages (13-17 years and 18-23 years), lower CD4 (<200 and 200-499/µL), and among those prescribed ARVs. Rates of ED visits and inpatient days were higher during PT spent at older ages (18-23 years and 24-30 years), lower CD4 (<200 and 200-499/µL), and VL ≥400 c/mL. Utilization was higher among PHIVY than NPHIVY (outpatient: 12.1 vs. 6.0/PY; ED: 0.4 vs. 0.3/PY; inpatient: 1.5 vs. 0.8/PY). CONCLUSIONS: More ED visits and inpatient days were observed during time spent at older ages, lower CD4 count, and VL ≥400 c/mL. Interventions to improve virologic suppression and immune response may improve outcomes, and thus decrease costly resource utilization, for AYA with HIV.


Assuntos
Envelhecimento , Infecções por HIV/tratamento farmacológico , Adolescente , Adulto , Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4 , Esquema de Medicação , Feminino , HIV-1 , Humanos , Masculino , Adesão à Medicação , Carga Viral , Adulto Jovem
17.
J Int AIDS Soc ; 22(6): e25326, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31243898

RESUMO

INTRODUCTION: Changes to the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) funding have led to closures of non-governmental HIV clinics with patient transfers to government-funded clinics. We sought to determine the success of transfers in South Africa using a national data source. METHODS: All adults (≥18 years) on antiretroviral therapy (ART) who visited a single PEPFAR-funded hospital-based HIV clinic in Durban, South Africa from March to June 2012 were transferred to community-based clinics. Previously, we matched patient records from the hospital-based HIV clinic with National Health Laboratory Services (NHLS) Corporate Data Warehouse (CDW) data to estimate the proportion of patients with a CD4 count or viral load (VL) in the CDW during the year before transfer. As a proxy for retention in care, in this study we evaluated whether patients had a CD4 count or VL at another facility within approximately three years of transfer. Patients referred to a private doctor at transfer were excluded from the analysis. We assessed predictors (age, sex, CD4 count, VL status, ART duration and location of future care) of not having post-transfer laboratory data using Cox proportional hazards models. RESULTS: Of the 3893 patients referred to a government facility at transfer, 41% were male and median age was 39 years (IQR 34 to 46). There was a post-transfer CD4 count or VL from another facility for 23% of these individuals within six months, 44% within one year, 57% within two years and 61% within approximately three years. Male sex (aHR 1.20, 95% CI 1.10 to 1.31) and shorter duration on ART (<3 months, aHR 3.80, 95% CI 2.77 to 5.21; three months to one year, aHR 1.32, 95% CI 1.15 to 1.51, each compared with >1 year) were associated with not having a post-transfer record. CONCLUSIONS: Using data from the NHLS CDW, 61% of patients had evidence of a post-transfer laboratory record at another facility within approximately three years after closure of a large South African HIV clinic. Males and those with shorter time on ART prior to transfer were at highest risk for lacking follow-up laboratory data. As patients transfer care, national data sources can be used to evaluate long-term patient care trajectories.


Assuntos
Infecções por HIV/terapia , Transferência de Pacientes/estatística & dados numéricos , Adulto , Instituições de Assistência Ambulatorial/estatística & dados numéricos , Contagem de Linfócito CD4 , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , África do Sul/epidemiologia
18.
PLoS One ; 14(6): e0219068, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31247009

RESUMO

INTRODUCTION: The Temprano and START trials provided evidence to support early ART initiation recommendations. We projected long-term clinical and economic outcomes of immediate ART initiation in Côte d'Ivoire. METHODS: We used a mathematical model to compare three potential ART initiation criteria: 1) CD4 <350/µL (ART<350/µL); 2) CD4 <500/µL (ART<500/µL); and 3) ART at presentation (Immediate ART). Outcomes from the model included life expectancy, 10-year medical resource use, incremental cost-effectiveness ratios (ICERs) in $/year of life saved (YLS), and 5-year budget impact. We simulated people with HIV (PWH) in care (mean CD4: 259/µL, SD 198/µL) and transmitted cases. Key input parameters to the analysis included first-line ART efficacy (80% suppression at 6 months) and ART cost ($90/person-year). We assessed cost-effectiveness relative to Côte d'Ivoire's 2017 per capita annual gross domestic product ($1,600). RESULTS: Immediate ART increased life expectancy by 0.34 years compared to ART<350/µL and 0.17 years compared to ART<500/µL. Immediate ART resulted in 4,500 fewer 10-year transmissions per 170,000 PWH compared to ART<350/µL. In cost-effectiveness analysis, Immediate ART had a 10-year ICER of $680/YLS compared to ART<350/µL, ranging from cost-saving to an ICER of $1,440/YLS as transmission rates varied. ART<500/µL was "dominated" (an inefficient use of resources), compared with Immediate ART. Immediate ART increased the 5-year HIV care budget from $801.9M to $812.6M compared to ART<350/µL. CONCLUSIONS: In Côte d'Ivoire, immediate compared to later ART initiation will increase life expectancy, decrease HIV transmission, and be cost-effective over the long-term, with modest budget impact. Immediate ART initiation is an appropriate, high-value standard of care in Côte d'Ivoire and similar settings.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/economia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/economia , Adolescente , Adulto , Orçamentos , Contagem de Linfócito CD4 , Estudos de Coortes , Simulação por Computador , Análise Custo-Benefício , Côte d'Ivoire , Custos de Medicamentos , Feminino , Infecções por HIV/imunologia , Recursos em Saúde/economia , Humanos , Expectativa de Vida , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Modelos Econômicos , Resultado do Tratamento , Adulto Jovem
19.
J Int AIDS Soc ; 22(4): e25274, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30990252

RESUMO

INTRODUCTION: People with HIV (PWH) are at increased risk for atherosclerotic cardiovascular disease (CVD). Screening for CVD risk factors is recommended but not routine in South African HIV clinics. We sought to describe the prevalence of CVD risk factors among antiretroviral treatment (ART)-experienced patients in South Africa. METHODS: We performed a prospective, observational cross-sectional study of PWH (>21 years, excluding pregnant women) on ART in South Africa. We interviewed patients regarding CVD risk factors, and obtained two blood pressure (BP) measurements and random/fasting glucose via a point-of-care glucometer. Standardized chart reviews provided individuals' HIV-specific data. We defined hypertension as: self-reported use of antihypertensives or mean systolic BP (SBP) ≥140 mmHg or diastolic BP (DBP) ≥90 mmHg (Stage 1) or SBP ≥160 mmHg or DBP ≥100 mmHg (Stage 2). We defined diabetes as self-reported use of insulin/oral hypoglycaemics or fasting (random) glucose ≥7.0 (≥11.1) mmol. We obtained risk ratios (RR) for hypertension from a multivariable log-binomial regression model, adjusting for age, sex and diabetes. RESULTS: From March 2015 to February 2016, 458 participants enrolled with median age 38 years (interquartile range (IQR) 33 to 44 years) and median CD4 466/µL (IQR 317 to 638/µL); 78% were women. Participants were on ART for a median of four years, with 33% on ART ≥6 years. Almost a quarter (106/458) met the study definition for hypertension, of whom 45/106 (42%) were previously diagnosed, 23/45 (51%) were on medication and 4/23 (17%) were controlled. Eight participants had asymptomatic hypertensive urgency (BP≥180/110 mmHg). Of the 458 participants, 26 (6%) met the study definition for diabetes, half of whom (13/26) were already diagnosed; 11/13 (85%) were on treatment, of whom 4/11 (36%) had normal glucose. Age was the only significant predictor of hypertension (RR, 1.04; 95% CI, 1.03 to 1.06, p < 0.0001) in the multivariable model. CONCLUSIONS: Hypertension and diabetes were prevalent among PWH prescribed ART in South Africa with less than half diagnosed, and still fewer treated and controlled. Hypertension was independently associated with age but not with HIV-specific factors. Screening for and treatment of CVD risk factors could decrease future morbidity and mortality, especially as this population ages.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/complicações , Hipertensão/etiologia , Adulto , Pressão Sanguínea , Estudos Transversais , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia , Diabetes Mellitus/metabolismo , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Masculino , Gravidez , Prevalência , Estudos Prospectivos , Fatores de Risco , África do Sul/epidemiologia
20.
BMJ Open ; 8(8): e021506, 2018 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-30139898

RESUMO

OBJECTIVE: To assess the accuracy of the South African National Health Laboratory Services (NHLS) corporate data warehouse (CDW) using a novel data cross-matching method. METHODS: Adults (≥18 years) on antiretroviral therapy (ART) who visited a hospital-based HIV clinic in Durban from March to June 2012 were included. We matched patient identifiers, CD4 and viral load (VL) records from the HIV clinic's electronic record with the NHLS CDW according to a set of matching criteria for patient identifiers, test values and test dates. We calculated the matching rates for patient identifiers, CD4 and VL records, and an overall matching rate. RESULTS: NHLS returned records for 3498 (89.6%) of the 3906 individuals requested. Using our computer algorithm, we confidently matched 3278 patients (83.9% of the total request). Considering less than confident matches as well, and then manually reviewing questionable matches using only patient identifiers, only nine (0.3% of records returned by NHLS) of the suggested matches were judged incorrect. CONCLUSIONS: We developed a data cross-matching method to evaluate national laboratory data and were able to match almost 9 of 10 patients with data we expected to find in the NHLS CDW. We found few questionable matches, suggesting that manual review of records returned was not essential. As the number of patients initiating ART in South Africa grows, maintaining a comprehensive and accurate national data repository is of critical importance, since it may serve as a valuable tool to evaluate the effectiveness of the country's HIV care system. This study helps validate the use of NHLS CDW data in future research on South Africa's HIV care system and may inform analyses in similar settings with national laboratory systems.


Assuntos
Contagem de Linfócito CD4 , Confiabilidade dos Dados , Infecções por HIV/sangue , Carga Viral , Adulto , Algoritmos , Antirretrovirais/uso terapêutico , Estudos Transversais , Monitoramento de Medicamentos , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , África do Sul/epidemiologia
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