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The Lancet. Global Health Apr 2021Increasing access to hepatitis C virus (HCV) care and treatment will require simplified service delivery models. We aimed to evaluate the effects of decentralisation and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Increasing access to hepatitis C virus (HCV) care and treatment will require simplified service delivery models. We aimed to evaluate the effects of decentralisation and integration of testing, care, and treatment with harm-reduction and other services, and task-shifting to non-specialists on outcomes across the HCV care continuum.
METHODS
For this systematic review and meta-analysis, we searched PubMed, Embase, WHO Global Index Medicus, and conference abstracts for studies published between Jan 1, 2008, and Feb 20, 2018, that evaluated uptake of HCV testing, linkage to care, treatment, cure assessment, and sustained virological response at 12 weeks (SVR12) in people who inject drugs, people in prisons, people living with HIV, and the general population. Randomised controlled trials, non-randomised studies, and observational studies were eligible for inclusion. Studies with a sample size of ten or less for the largest denominator were excluded. Studies were categorised according to the level of decentralisation: full (testing and treatment at same site), partial (testing at decentralised site and referral elsewhere for treatment), or none. Task-shifting was categorised as treatment by specialists or non-specialists. Data on outcomes across the HCV care continuum (linkage to care, treatment uptake, and SVR12) were pooled using random-effects meta-analysis.
FINDINGS
Our search identified 8050 reports, of which 132 met the eligibility criteria, and an additional ten reports were identified from reference citations and grey literature. Therefore, the final synthesis included 142 studies from 34 countries (20 [14%] studies from low-income and middle-income countries) and a total of 489 996 patients (239 446 [49%] from low-income and middle-income countries). Rates of linkage to care were higher with full decentralisation compared with partial or no decentralisation among people who inject drugs (full 72% [95% CI 57-85] vs partial 53% [38-67] vs none 47% [11-84]) and among people in prisons (full 94% [79-100] vs partial 50% [29-71]), although the CIs overlap for people who inject drugs. Similarly, treatment uptake was higher with full decentralisation compared with partial or no decentralisation (people who inject drugs: full 73% [65-80] vs partial 66% [55-77] vs none 35% [23-48]; people in prisons: full 72% [48-91] vs partial 39% [17-63]), although CIs overlap for full versus partial decentralisation. The results in the general population studies were more heterogeneous. SVR12 rates were high (≥90%) across different levels of decentralisation in all populations. Task-shifting of care and treatment to a non-specialist was associated with similar SVR12 rates to treatment delivered by specialists. There was a severe or critical risk of bias for 46% of studies, and heterogeneity across studies tended to be very high (I>90%).
INTERPRETATION
Decentralisation and integration of HCV care to harm-reduction sites or primary care showed some evidence of improved access to testing, linkage to care, and treatment, and task-shifting of care and treatment to non-specialists was associated with similarly high cure rates to care delivered by specialists, across a range of populations and settings. These findings provide support for the adoption of decentralisation and task-shifting to non-specialists in national HCV programmes.
FUNDING
Unitaid.
Topics: Antiviral Agents; Delivery of Health Care, Integrated; Health Services Accessibility; Hepacivirus; Hepatitis C; Humans; Models, Organizational; National Health Programs; Observational Studies as Topic; Patient Acceptance of Health Care; Randomized Controlled Trials as Topic; Sustained Virologic Response
PubMed: 33639097
DOI: 10.1016/S2214-109X(20)30505-2 -
Vaccines May 2023The COVID-19 vaccination is a crucial public health intervention for controlling the spread and severity of the SARS-CoV2 virus. COVID-19 vaccines have been developed in... (Review)
Review
The COVID-19 vaccination is a crucial public health intervention for controlling the spread and severity of the SARS-CoV2 virus. COVID-19 vaccines have been developed in record time, but their deployment has varied across countries, owing to differences in health system capacity, demand for the vaccine, and purchasing power of countries. The aim of this rapid review is to summarize and synthesize experiences on COVID-19 vaccine service delivery and integration to inform future COVID-19 vaccination programming and contribute to the knowledge base for future pandemic management. A systematic search was conducted in PubMed, Scopus, and Global Index Medicus databases. Twenty-five studies were included in the analysis. Included studies spanned nine countries where COVID-19 vaccines were delivered through mass, mobile, and fixed-post vaccination service delivery models. There was limited evidence of integrating COVID-19 vaccines into routine services for pregnant women, people who inject drugs, and leveraging existing health programs to deliver COVID-19 vaccines to the general population. Common challenges reported were vaccine skepticism, lack of adequate health workers, and linguistic barriers to access. Partnerships with a variety of stakeholders and the involvement of volunteers were vital in overcoming barriers and contributed to the efficient functioning of COVID-19 vaccination programs.
PubMed: 37243078
DOI: 10.3390/vaccines11050974 -
Cancer Treatment Reviews Jun 2024Gastric cancer (GC), known for its unfavorable prognosis, has been classified in four distinct molecular subtypes. These subtypes not only exhibit differences in their... (Review)
Review
BACKGROUND
Gastric cancer (GC), known for its unfavorable prognosis, has been classified in four distinct molecular subtypes. These subtypes not only exhibit differences in their genome and transcriptome but also in the composition of their tumor immune microenvironment. The microsatellite instable (MSI) and Epstein-Barr virus (EBV) positive GC subtypes show clear clinical benefits from immune checkpoint blockade, likely due to a neoantigen-driven and virus-driven antitumor immune response and high expression of immune checkpoint molecule PD-L1. However, even within these subtypes response to checkpoint inhibition is variable, which is potentially related to heterogeneity in the tumor immune microenvironment (TIME) and expression of co-inhibitory molecules. We conducted a systematic review to outline the current knowledge about the immunological features on the TIME of MSI and EBV + GCs.
METHODS
A systematic search was performed in PubMed, EMBASE and Cochrane Library. All articles from the year 1990 and onwards addressing immune features of gastric adenocarcinoma were reviewed and included based on predefined in- and exclusion criteria.
RESULTS
In total 5962 records were screened, of which 139 were included that reported immunological data on molecular GC subtypes. MSI and EBV + GCs were reported to have a more inflamed TIME compared to non-MSI and EBV- GC subtypes. Compared to microsatellite stable (MSS) tumors, MSI tumors were characterized by higher numbers of CD8 + and FoxP3 + T cells, and tumor infiltrating pro- and anti-inflammatory macrophages. HLA-deficiency was most common in MSI tumors compared to other molecular GC subtypes and associated with lower T and B cell infiltrates compared to HLA-proficient tumors. EBV + was associated with a high number of CD8 + T cells, Tregs, NK cells and macrophages. Expression of PD-L1, CTLA-4, Granzyme A and B, Perforin and interferon-gamma was enriched in EBV + tumors. Overall, MSI tumors harbored a more heterogeneous TIME in terms of immune cell composition and immune checkpoints compared to the EBV + tumors.
DISCUSSION AND CONCLUSION
MSI and EBV + GCs are highly Handbook for Conducting a Literature-Based Health Assessment Using OHAT Approach for Systematic Review and Evidence Integration.; 2019pro-inflammatory immune cell populations. Although studies on the direct comparison of EBV + and MSI tumors are limited, EBV + tumors show less intra-subgroup heterogeneity compared to MSI tumors. More studies are needed to identify how Intra-subgroup heterogeneity impacts response to immunotherapy efficacy.
Topics: Humans; Stomach Neoplasms; Tumor Microenvironment; Epstein-Barr Virus Infections; DNA Mismatch Repair; Herpesvirus 4, Human; Microsatellite Instability
PubMed: 38669788
DOI: 10.1016/j.ctrv.2024.102737 -
Expert Review of Vaccines Sep 2019: In Asia Pacific, most countries recommend a monovalent hepatitis B virus (HBV) vaccine dose at birth followed by primary vaccination series including three or four...
Integration of hexavalent diphtheria, tetanus, acellular pertussis, hepatitis B virus, inactivated poliomyelitis and Haemophilus influenzae type b conjugate vaccine within existing national recommendations following a birth dose of monovalent hepatitis B virus vaccine: results of a systematic...
: In Asia Pacific, most countries recommend a monovalent hepatitis B virus (HBV) vaccine dose at birth followed by primary vaccination series including three or four doses of combination vaccines against diphtheria, tetanus, and pertussis, with or without type b (Hib), HBV or poliomyelitis antigens. If hexavalent conjugate vaccines against diphtheria-tetanus-acellular pertussis-HBV-inactivated poliovirus-Hib (DTPa-HBV-IPV/Hib) replace the vaccines included in the primary vaccination series, co-administration of lower-valent vaccines would be avoided but infants would receive ≥4 doses of HBV-containing vaccines before the age of 2 years. : We searched for clinical trials conducted in the South-East Asia and Western Pacific Regions (World Health Organization geographic definition), investigating vaccination regimens with >3 doses of HBV-containing vaccines in infants, including a monovalent HBV vaccine birth dose and ≥1 dose of GSK's hexavalent DTPa-HBV-IPV/Hib vaccine. : The six clinical trials included in this review showed that infants who received the monovalent HBV vaccine at birth and three or four doses of DTPa-HBV-IPV/Hib vaccine achieved protective immunogenic titers with a clinically acceptable safety profile. Our results support the integration of hexavalent DTPa-HBV-IPV/Hib vaccine within existing national recommendations in the Asia Pacific region to reduce the number of injections during infancy.
Topics: Databases, Factual; Diphtheria; Diphtheria-Tetanus-acellular Pertussis Vaccines; Haemophilus Infections; Haemophilus influenzae type b; Hepatitis B; Hepatitis B Vaccines; Hepatitis B virus; Humans; Immunization Schedule; Poliomyelitis; Tetanus; Vaccines, Combined; Vaccines, Conjugate; Whooping Cough
PubMed: 31328999
DOI: 10.1080/14760584.2019.1646643 -
Frontiers in Bioscience (Landmark... Jun 2022The purpose of this manuscript is to provide a comparative overview of the two global pandemics: the first on June 11th 2009 due to influenza A H1N1 (H1N1-09); the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The purpose of this manuscript is to provide a comparative overview of the two global pandemics: the first on June 11th 2009 due to influenza A H1N1 (H1N1-09); the second and current pandemic caused by coronavirus 2019 (COVID-19) on March 11th 2020, focusing on how autopsy can contribute to the definition of cellular pathology, to clinical pathology and, more generally, to public health.
METHODS
A systematic literature search selection was conducted on PubMed database on June 5, 2021, with this search strategy: (COVID-19) AND (H1N1 influenza) showing 101 results. The following inclusion criteria were selected: English language; published in a scholarly peer-reviewed journal; full-length articles were further elected. To further refine the research was to focus on the type of manuscript: review, systematic review, and meta-analysis. A critical appraisal of the collected studies was conducted, analyzing titles and abstracts, excluding the following topics: treatment, public health measures and perception of the general population or healthcare personnel about their quality of life. According to these procedures, 54 eligible studies were included in the present review.
RESULTS
Histopathological findings play a key role in understanding the pathophysiological mechanisms of diseases and, thus possible therapeutic approaches. The evidence on the thrombo-inflammatory mechanism underlying COVID-19 is growing to a much greater magnitude than the diffuse alveolar damage in common with H1N1-09; our study appears to be in line with these results. The prevailing scientific thinking to explain the morbidity and mortality of COVID-19 patients is that it elicits an exuberant immune reaction characterized by dysregulated cytokine production, known as a "cytokine storm".
CONCLUSIONS
The histological and immunohistochemical pattern demonstrated similarities and differences between the infectious manifestations of the two pathogens, which justify empirical therapeutic approaches, in the first phase of the COVID-19 pandemic. Therefore, the previous pandemic should have taught us to promote a culture of clinical and forensic autopsies in order to provide timely evidence from integration among autopsy and clinical data for early adopting adequate therapies.
Topics: Autopsy; COVID-19; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Lung; Pandemics; Quality of Life
PubMed: 35748258
DOI: 10.31083/j.fbl2706182 -
Fertility and Sterility Mar 2016To evaluate the effectiveness of semen washing in human immunodeficiency virus (HIV)-discordant couples in which the male partner is infected. (Meta-Analysis)
Meta-Analysis Review
Effectiveness of semen washing to prevent human immunodeficiency virus (HIV) transmission and assist pregnancy in HIV-discordant couples: a systematic review and meta-analysis.
OBJECTIVE
To evaluate the effectiveness of semen washing in human immunodeficiency virus (HIV)-discordant couples in which the male partner is infected.
DESIGN
Systematic review and meta-analysis.
SETTING
Not applicable.
PATIENT(S)
Forty single-arm open-label studies among HIV-discordant couples that underwent intrauterine insemination (IUI) or in vitro fertilization (IVF) with or without intracytoplasmic sperm injection (ICSI) using washed semen.
INTERVENTION(S)
Semen washing followed by IUI, IVF, or IVF/ICSI.
PRIMARY OUTCOME
HIV transmission to HIV-uninfected women; secondary outcomes: HIV transmission to newborns and proportion of couples achieving a clinical pregnancy.
RESULT(S)
No HIV transmission occurred in 11,585 cycles of assisted reproduction with the use of washed semen among 3,994 women. Among the subset of HIV-infected men without plasma viral suppression at the time of semen washing, no HIV seroconversions occurred among 1,023 women after 2,863 cycles of assisted reproduction with the use of washed semen. Studies that measured HIV transmission to infants reported no cases of vertical transmission. Overall, 56.3% of couples (2,357/4,184) achieved a clinical pregnancy with the use of washed semen.
CONCLUSION(S)
Semen washing appears to significantly reduce the risk of transmission in HIV-discordant couples desiring children, regardless of viral suppression in the male partner. There are no randomized controlled studies or studies from low-income countries, especially those with a large burden of HIV. Continued development of lower-cost semen washing and assisted reproduction technologies is needed. Integration of semen washing into HIV prevention interventions could help to further reduce the spread of HIV.
Topics: Adult; Female; Fertilization in Vitro; HIV; HIV Infections; HIV Seronegativity; HIV Seropositivity; Humans; Infectious Disease Transmission, Vertical; Insemination, Artificial; Male; Middle Aged; Pregnancy; Pregnancy Rate; Risk Factors; Sperm Injections, Intracytoplasmic; Sperm Retrieval; Spermatozoa; Treatment Outcome
PubMed: 26688556
DOI: 10.1016/j.fertnstert.2015.11.028 -
Human Cell Mar 2022The Proviral Integration of Molony murine leukemia virus (PIM)-1 protein contributes to the solid cancers and hematologic malignancies, cell growth, proliferation,... (Review)
Review
The Proviral Integration of Molony murine leukemia virus (PIM)-1 protein contributes to the solid cancers and hematologic malignancies, cell growth, proliferation, differentiation, migration, and other life activities. Many studies have related these functions to its molecular structure, subcellular localization and expression level. However, recognition of specific active sites and their effects on the activity of this constitutively active kinase is still a challenge. Based on the close relationship between its molecular structure and functional activity, this review covers the specific residues involved in the binding of ATP and different substrates in its catalytic domain. This review then elaborates on the relevant changes in protein conformation and cell functions after PIM-1 binds to different substrates. Therefore, this intensive study can improve the understanding of PIM-1-regulated signaling pathways by facilitating the discovery of its potential phosphorylation substrates.
Topics: Animals; Catalytic Domain; Cell Proliferation; Hematologic Neoplasms; Mice; Phosphorylation; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-pim-1
PubMed: 35000143
DOI: 10.1007/s13577-021-00656-3 -
Cancer Research Jun 2004Cancers of the anogenital tract as well as some head and neck cancers are caused by persistent infections with high-risk type human papillomaviruses (HPVs). Two viral... (Review)
Review
Cancers of the anogenital tract as well as some head and neck cancers are caused by persistent infections with high-risk type human papillomaviruses (HPVs). Two viral oncogenes, E6 and E7, induce severe chromosomal instability associated with centrosome aberrations, anaphase bridges, chromosome lagging, and breaking. This occurs early in preneoplastic lesions, when the viral genome still persists in an episomal state. In most invasive cancers and also in a few high-grade dysplastic lesions, however, integration of high-risk HPV genomes into the host genome is observed. Integration seems to be a direct consequence of chromosomal instability and an important molecular event in the progression of preneoplastic lesions. Disruption or deregulation of defined critical cellular gene functions by insertional mutagenesis by integrated HPV genome fragments has been hypothesized as one major promoting factor in the pathogenesis of HPV-associated cancers. This hypothesis was based on the detection of HPV integration events in the area of tumor-relevant genes in few cases. Here, we reviewed >190 reported integration loci with respect to changes in the viral structure and the targeted genomic locus. This analysis confirms that HPV integration sites are randomly distributed over the whole genome with a clear predilection for genomic fragile sites. No evidence for targeted disruption or functional alteration of critical cellular genes by the integrated viral sequences could be found.
Topics: Cell Transformation, Viral; DNA, Viral; Epithelial Cells; Female; Gene Expression Regulation, Viral; Genital Neoplasms, Female; Humans; In Situ Hybridization, Fluorescence; Papillomaviridae; Uterine Cervical Neoplasms; Vaginal Neoplasms; Virus Integration; Vulvar Neoplasms; Uterine Cervical Dysplasia
PubMed: 15172997
DOI: 10.1158/0008-5472.CAN-04-0009 -
Journal of Gastroenterology and... Sep 2020Various all-oral direct-acting antiviral (DAA) regimens are being widely used in the treatment of human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infected... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIM
Various all-oral direct-acting antiviral (DAA) regimens are being widely used in the treatment of human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infected patients; however, the comparative efficacy and safety of different types and combinations of DAAs are not completely clear. There is still a lack of integration of evidence for optimized therapies for HIV/HCV co-infection.
METHODS
We conducted a systematic literature search in several databases up to January 1, 2020. All the studies that reported the sustained virologic response (SVR) and adverse events of DAAs in HIV/HCV co-infected patients were included. The Bayesian Markov Chain Monte Carlo method was used for the pooled estimates of network meta-analysis.
RESULTS
We identified 33 eligible articles with 7 combinations of all-oral DAAs for the analyses of efficacy and safety. Grazoprevir-elbasvir ± ribavirin (GZR/EBR ± RBV: 95.6%; 95% CrI, 91.7-98.1%), ombitasvir/paritaprevir/ritonavir and dasabuvir ± ribavirin (3D ± RBV: 95.3%; 95% CrI, 93.4-96.9%), sofosbuvir-ledipasvir ± ribavirin (SOF/LDV ± RBV: 95.2%; 95% CrI, 93.7-96.6%), and sofosbuvir-daclatasvir ± ribavirin (SOF/DCV ± RBV: 94.8%; 95% CrI, 92.5-96.6%) were the most effective combinations for HIV/HCV co-infected patients, with SVR rates of approximately 94% and above while severe adverse events were rare. However, the SVR rates of sofosbuvir-ribavirin (SOF/RBV) and sofosbuvir-simeprevir ± ribavirin (SOF/SMV ± RBV) both failed to reach 90%, and the incidences of adverse events were higher than 5%.
CONCLUSIONS
Efficacy and safety of all-oral DAAs were in prospect for HIV/HCV co-infection patients. GZR/EBR ± RBV was the optimal combination recommended for HIV/HCV co-infected patients based on the excellent treatment effects and insignificant adverse events.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Coinfection; Cyclopropanes; Drug Therapy, Combination; Female; HIV Infections; Hepatitis C, Chronic; Humans; Imidazoles; Male; Middle Aged; Quinoxalines; Ribavirin; Safety; Sulfonamides; Sustained Virologic Response; Treatment Outcome
PubMed: 32246857
DOI: 10.1111/jgh.15051 -
The International Journal on Drug Policy Oct 2019Despite the key role that people who inject drugs (PWID) play in the hepatitis C virus (HCV) epidemic, HCV treatment rates among this population have been historically...
BACKGROUND
Despite the key role that people who inject drugs (PWID) play in the hepatitis C virus (HCV) epidemic, HCV treatment rates among this population have been historically low. Integrated models of HCV and substance use care have the potential to overcome some barriers to access; however, the evidence base is uncertain. This systematic review assesses the impacts of integrated HCV and substance use services on engagement in HCV care among PWID.
METHODS
We searched five databases up to December 2018 to identify original quantitative studies evaluating the impacts of co-location of HCV and substance use services on engagement in the HCV cascade of care among adult PWID. We conducted a narrative synthesis, categorizing models based on patient entry point (a: HCV facility, b: substance use disorder (SUD) facility, and c: other facilities), and levels of integrated services offered (a: HCV/substance use testing only, b: HCV/substance use treatment, and c: testing/treatment + other services).
RESULTS
A total of 46 articles corresponding to 44 original studies were included. Almost all studies (n = 42) were conducted in high-income countries and only six studies in the Direct-Acting Antiviral (DAA) era. Twenty-six studies discussed the integration of services at SUD facilities, one at HCV facilities, and seventeen at other facilities. Analysis of included studies indicated that overall integrated care resulted in improved engagement in HCV care (e.g., testing, treatment uptake and cure). However, the quality of evidence was predominantly low to moderate.
CONCLUSIONS
Available evidence suggests that integration of HCV and substance use services may improve engagement along the continuum of HCV care among PWID. Given limitations in data quality, and very few studies conducted in the DAA era and in low- and middle-income settings, further research is urgently needed to inform strategies to optimize HCV care access and outcomes among PWID globally.
Topics: Adult; Antiviral Agents; Delivery of Health Care, Integrated; Hepatitis C, Chronic; Humans; Substance Abuse, Intravenous
PubMed: 31147142
DOI: 10.1016/j.drugpo.2019.05.023