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Cureus Mar 2024Advanced pancreatic cancer is one of the prominent contributors to cancer-related mortality globally. Chemotherapy, especially gemcitabine, is generally used for the... (Review)
Review
Advanced pancreatic cancer is one of the prominent contributors to cancer-related mortality globally. Chemotherapy, especially gemcitabine, is generally used for the treatment of advanced pancreatic cancer. Despite the treatment, the fatality rate for advanced pancreatic cancer is alarmingly high. Thus, the dire need for better treatment alternatives has drawn focus to cancer vaccinations. The Wilms tumor gene (WT1), typically associated with Wilms tumor, is found to be excessively expressed in some cancers, such as pancreatic cancer. This characteristic feature is harvested to develop cancer vaccines against WT1. This review aims to systematically summarize the clinical trials investigating the efficacy and safety of WT1 vaccines in patients with advanced pancreatic cancer. An extensive literature search was conducted on databases Medline, Web of Science, ScienceDirect, and Google Scholar using the keywords "Advanced pancreatic cancer," "Cancer vaccines," "WT1 vaccines," and "Pulsed DC vaccines," and the results were exclusively studied to construct this review. WT1 vaccines work by introducing peptides from the WT1 protein to trigger an immune response involving cytotoxic T lymphocytes via antigen-presenting cells. Upon activation, these lymphocytes induce apoptosis in cancer cells by specifically targeting those with increased WT1 levels. WT1 vaccinations, which are usually given in addition to chemotherapy, have demonstrated clinically positive results and minimal side effects. However, there are several challenges to their widespread use, such as the immunosuppressive nature of tumors and heterogeneity in expression. Despite these limitations, the risk-benefit profile of cancer vaccines is encouraging, especially for the WT1 vaccine in the treatment of advanced pancreatic cancer. Considering the fledgling status of their development, large multicentric, variables-matched, extensive analysis across diverse demographics is considered essential.
PubMed: 38665761
DOI: 10.7759/cureus.56934 -
Clinical Microbiology and Infection :... Apr 2024Tuberculosis (TB) is a common complication associated with treatment with tumour necrosis factor (TNF) antagonists and Janus kinase (JAK) inhibitors. However, there is... (Review)
Review
BACKGROUND
Tuberculosis (TB) is a common complication associated with treatment with tumour necrosis factor (TNF) antagonists and Janus kinase (JAK) inhibitors. However, there is uncertainty about the risk of TB relapse in patients with TB and comorbidities requiring treatment with these agents.
OBJECTIVES
To assess the risk of TB relapse in patients (re-)started on TNF antagonists or JAK inhibitors.
METHODS
Systematic review.
DATA SOURCES
PubMed and Cochrane Library databases until 11 December 2023.
STUDY ELIGIBILITY CRITERIA
Randomized control trials, prospective and retrospective cohort studies, case reports and case series.
PARTICIPANTS
Patients with current or previous TB who were (re-)started on TNF antagonists or JAK inhibitors.
INTERVENTIONS
(Re-)introduction of TNF antagonists and JAK inhibitors.
ASSESSMENT OF RISK OF BIAS
All studies meeting entry criteria were included regardless of quality.
METHODS OF DATA SYNTHESIS
Categorical data are presented as frequencies and percentages. For non-normally distributed aggregated data, we calculated the pooled weighted median with 95% CI. For individual patient data, the median and interquartile range (IQR) were calculated.
RESULTS
Of 5018 articles screened for eligibility, 67 publications reporting on 368 TB patients who (re-)initiated treatment with TNF antagonists for underlying diseases were included. The median age was 42.5 years (95% CI: 40.4-42.5) and the proportion of female patients was 36.6% (n = 74) of patients whose sex was reported. A total of 14 patients (3.8%, 95% CI: 2.1-6.3%) developed TB relapse after a median of 8.5 months (interquartile range, 6.8-14.8 months) following (re-)initiation of anti-TNF treatment. Furthermore, among 251 articles screened for eligibility, 11 reports on TB patients who were (re-)started on JAK inhibitors for underlying diseases were identified. The median age was 62 years (interquartile range, 48.5-68.5 years) and 45.5% (n = 5) were female. Only one patient (9.1%; 95% CI: 0.2-41.3%) had TB reactivation 10 months after starting treatment with ruxolitinib. In addition, 94 patients who were treated with TNF antagonists and two patients temporarily treated with JAK inhibitors for the prevention or treatment of paradoxical reactions were analysed. None of the publications reported microbiological failure or worsening of TB-related symptoms.
CONCLUSIONS
(Re-)initiation of TNF antagonists and JAK inhibitors may be relatively safe in patients with current or previous TB and the need for further treatment of underlying diseases.
PubMed: 38663653
DOI: 10.1016/j.cmi.2024.04.011 -
Immunity, Inflammation and Disease Apr 2024Immunocompromised individuals have been shown to mount a reduced response to vaccination, resulting in reduced vaccine effectiveness in this cohort. Therefore, in the... (Review)
Review
INTRODUCTION
Immunocompromised individuals have been shown to mount a reduced response to vaccination, resulting in reduced vaccine effectiveness in this cohort. Therefore, in the postvaccination era, immunocompromised individuals remain at high risk of breakthrough infection and COVID-19 related hospitalization and death, which persist despite vaccination efforts. There has been a marked paucity of systematic reviews evaluating existing data describing the clinical measures of efficacy of COVID-19 vaccination, specifically in immunocompromised populations. In particular, there is a scarcity of comprehensive evaluations exploring breakthrough infections and severe COVID-19 in this patient population.
METHODS
To address this gap, we conducted a systematic review which aimed to provide a summary of current clinical evidence of the effectiveness of COVID-19 vaccination in the immunocompromised population. Using PRISMA guidelines, we conducted a literature search on PubMed and the Cochrane database published between January 1, 2021 to September 1, 2022.
RESULTS
Our findings demonstrated that despite vaccination, immunocompromised patients remained at high risk of new breakthrough COVID-19 infection and severe COVID-19 outcomes compared to the general population. We found increased average relative risk (RR) of breakthrough infections in the immunocompromised population, including patients with cancer (RR = 1.4), HIV (RR = 1.92), chronic kidney disease (RR = 2.26), immunodeficiency (RR = 2.55), and organ transplant recipients (RR = 6.94). These patients are also at greater risk for hospitalizations and death following COVID-19 breakthrough infection. We found that the RR of hospitalization and death in Cancer patients was 1.08 and 2.82, respectively.
CONCLUSION
This demonstrated that vaccination does not offer an adequate level of protection in these groups, necessitating further measures such as Evusheld and further boosters.
Topics: Humans; Breakthrough Infections; COVID-19; COVID-19 Vaccines; Hospitalization; Immunocompromised Host; Neoplasms; Risk Factors; Vaccination; Vaccine Efficacy
PubMed: 38661301
DOI: 10.1002/iid3.1259 -
Frontiers in Public Health 2024Omicron (B.1.1.529), a variant of SARS-CoV-2, has emerged as a dominant strain in COVID-19 pandemic. This development has raised concerns about the effectiveness of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Omicron (B.1.1.529), a variant of SARS-CoV-2, has emerged as a dominant strain in COVID-19 pandemic. This development has raised concerns about the effectiveness of vaccination to Omicron, particularly in the context of children and adolescents. Our study evaluated the efficacy of different COVID-19 vaccination regimens in children and adolescents during the Omicron epidemic phase.
METHODS
We searched PubMed, Cochrane, Web of Science, and Embase electronic databases for studies published through March 2023 on the association between COVID-19 vaccination and vaccine effectiveness (VE) against SARS-CoV-2 infection in children and adolescents at the Omicron variant period. The effectiveness outcomes included mild COVID-19 and severe COVID-19. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was prospectively registered in PROSPERO (CRD42023390481).
RESULTS
A total of 33 studies involving 16,532,536 children were included in the analysis. First, in children and adolescents aged 0-19 years, the overall VE of the COVID-19 vaccine is 45% (95% confidence interval [CI]: 40 to 50%). Subgroup analysis of VE during Omicron epidemic phase for different dosage regimens demonstrated that the VE was 50% (95% CI: 44 to 55%) for the 2-dose vaccination and 61% (95% CI: 45 to 73%) for the booster vaccination. Upon further analysis of different effectiveness outcomes during the 2-dose vaccination showed that the VE was 41% (95% CI: 35 to 47%) against mild COVID-19 and 71% (95% CI: 60 to 79%) against severe COVID-19. In addition, VE exhibited a gradual decrease over time, with the significant decline in the efficacy of Omicron for infection before and after 90 days following the 2-dose vaccination, registering 54% (95% CI: 48 to 59%) and 34% (95% CI: 21 to 56%), respectively.
CONCLUSION
During the Omicron variant epidemic, the vaccine provided protection against SARS-CoV-2 infection in children and adolescents aged 0-19 years. Two doses of vaccination can provide effective protection severe COVID-19, with booster vaccination additionally enhancing VE.
Topics: Adolescent; Child; Child, Preschool; Humans; Infant; COVID-19; COVID-19 Vaccines; SARS-CoV-2; Vaccination; Vaccine Efficacy
PubMed: 38660347
DOI: 10.3389/fpubh.2024.1338208 -
Vaccine May 2024A global shift to bivalent mRNA vaccines is ongoing to counterbalance the diminishing effectiveness of the original monovalent vaccines due to the evolution of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A global shift to bivalent mRNA vaccines is ongoing to counterbalance the diminishing effectiveness of the original monovalent vaccines due to the evolution of SARS-CoV-2 variants, yet substantial variation in the bivalent vaccine effectiveness (VE) exists across studies and a complete picture is lacking.
METHODS
We searched papers evaluating absolute or relative effectiveness of SARS-CoV-2 BA.1 type or BA.4/5 type bivalent mRNA vaccines on eight publication databases published from September 1st, 2022, to November 8th, 2023. Pooled VE against Omicron-associated infection and severe events (hospitalization and/or death) was estimated in reference to unvaccinated, ≥2 original monovalent doses, and ≥ 3 original monovalent doses.
RESULTS
From 630 citations identified, 28 studies were included, involving 55,393,303 individuals. Bivalent boosters demonstrated higher effectiveness against symptomatic or any infection for all ages combined, with an absolute VE of 53.5 % (95 % CI: -22.2-82.3 %) when compared to unvaccinated and relative VE of 30.8 % (95 % CI: 22.5-38.2 %) and 28.4 % (95 % CI: 10.2-42.9 %) when compared to ≥ 2 and ≥ 3 original monovalent doses, respectively. The corresponding VE estimates for adults ≥ 60 years old were 22.5 % (95 % CI: 16.8-39.8 %), 31.4 % (95 % CI: 27.7-35.0 %), and 30.6 % (95 % CI: -13.2-57.5 %). Pooled bivalent VE estimates against severe events were higher, 72.9 % (95 % CI: 60.5-82.4 %), 57.6 % (95 % CI: 42.4-68.8 %), and 62.1 % (95 % CI: 54.6-68.3 %) for all ages, and 72.0 % (95 % CI: 51.4-83.9 %), 63.4 % (95 % CI: 41.0-77.3 %), and 60.7 % (95 % CI: 52.4-67.6 %) for adults ≥ 60 years old, compared to unvaccinated, ≥2 original monovalent doses, and ≥ 3 original monovalent doses, respectively.
CONCLUSIONS
The bivalent boosters demonstrated superior protection against severe outcomes than the original monovalent boosters across age groups, highlighting the critical need for improving vaccine coverage, especially among the vulnerable older subpopulation.
Topics: Humans; COVID-19 Vaccines; COVID-19; SARS-CoV-2; Vaccine Efficacy; Immunization, Secondary; mRNA Vaccines; Vaccines, Synthetic; Middle Aged; Adult
PubMed: 38653679
DOI: 10.1016/j.vaccine.2024.04.049 -
Human Vaccines & Immunotherapeutics Dec 2024Few papers focus their attention on VZV vaccination effectiveness among people living with HIV (PLWH). Flanking the live attenuated vaccine (VZL) available, a newly... (Review)
Review
Few papers focus their attention on VZV vaccination effectiveness among people living with HIV (PLWH). Flanking the live attenuated vaccine (VZL) available, a newly recombinant vaccine (RZV) was recently introduced and approved for HZ prevention among adults. PLWH represents a population on which a particular attention should be applied, in order to guarantee the vaccine efficacy and safety. We performed a literature search in USNLM, PubMed, PubMed Central, PMC and Cochrane Library. From all the publications found eligible, data were extracted and processed per population, vaccine type, immunogenicity and ADRs. The review of the 13 included studies shows that both RZV and VZL are immunogenic and have an acceptable safety profile in adults and children living with HIV. However, given the lack of research available about vaccine efficacy in preventing VZV and HZ in PLWH, additional studies need to be performed, in order to achieve a full completeness of data.
Topics: Humans; Vaccines, Attenuated; HIV Infections; Herpes Zoster Vaccine; Vaccines, Synthetic; Herpes Zoster; Vaccines, Inactivated; Immunogenicity, Vaccine; Vaccine Efficacy; Herpesvirus 3, Human; Adult; Child; Vaccination; Chickenpox Vaccine
PubMed: 38650460
DOI: 10.1080/21645515.2024.2341456 -
Journal of Medical Virology Apr 2024This study aimed to examine the safety, immunogenicity and protective effective of inhaled COVID-19 vaccines (ICVs). Literature research was done through EMBASE,... (Meta-Analysis)
Meta-Analysis Review
This study aimed to examine the safety, immunogenicity and protective effective of inhaled COVID-19 vaccines (ICVs). Literature research was done through EMBASE, Cochrane, PubMed, and Web of Science up to 10 March 2024. Pooled estimates with corresponding 95% confidence intervals (CI) were computed and compared using the random effects and common effects model. Of the 15 studies, 11 analyzed safety, 13 analyzed immunogenicity, and 3 analyzed protective effective. The results showed a favorable safety profile of ICVs for primary vaccination series, however it does not always seem to produce the expected immune response and protective effective. Meta-analysis of ICVs booster vaccinations (BVs) showed that the levels of neutralizing antibody Geometric mean titer (nAb-GMT) with aerosolised Ad5-nCoV (AAd5-nCoV) were all higher than those with inactivated vaccine (INA-nCoV) (standard mean difference (SMD) = 2.32; 95% CI: 1.96-2.69) and intramuscular Ad5-nCoV (IMAd5-nCoV) (SMD = 0.31; 95% CI: 0.14-0.48) against the original strain of SARS-CoV-2. Importantly, we also observed similar results in the omicron variant. In addition, ICV in BVs has high mucosal immunity to IgA antibodies. The risk of adverse events was comparable or lower for AAd5-nCoV compared to INA-nCoV or IMAd5-nCoV. Current evidence shows that the safety profile of ICVs were well. The booster dose of AAd5-nCoV had a high immune response (including mucosal immunity) and provided protection against COVID-19 caused by the SARS-CoV-2 omicron variant. Further studies are needed to investigate the long-term safety of intranasal vaccine booster protection and various types of ICVs.
Topics: Humans; COVID-19 Vaccines; COVID-19; Antibodies, Neutralizing; Antibodies, Viral; SARS-CoV-2; Administration, Inhalation; Immunogenicity, Vaccine; Immunization, Secondary; Vaccination; Vaccines, Inactivated; Vaccine Efficacy
PubMed: 38650361
DOI: 10.1002/jmv.29625 -
European Urology Focus Apr 2024Several bacterial immunisations have been developed to reduce the socioeconomic burden of urinary tract infections (UTIs) and the use of prophylactic antibiotics in the... (Review)
Review
BACKGROUND AND OBJECTIVE
Several bacterial immunisations have been developed to reduce the socioeconomic burden of urinary tract infections (UTIs) and the use of prophylactic antibiotics in the management of recurrent UTIs (rUTIs). This systematic review evaluates the effectiveness of vaccinations in preventing rUTIs.
METHODS
Medline, Embase, and Web of Science were searched from inception to December 2023. Data were collected from cohort studies with a comparator arm and randomised controlled trials (RCTs) investigating vaccination efficacy in adult rUTI patients according to predefined selection criteria (PROSPERO registration: CRD42022356662). A pooled analysis took place for RCTs, with a subgroup analysis for vaccine types and booster regimens. Other studies were synthesised narratively. The risk of bias was assessed using Cochrane Risk-of-Bias tools. The Grading of Recommendations, Assessment, Development, and Evaluations framework evaluated the quality of evidence.
KEY FINDINGS AND LIMITATIONS
Fourteen comparative studies were selected, including 2822 patients across five vaccination types. The pooled risk ratio of eight placebo-controlled studies of the percentage of patients UTI free in the short term (6-12 mo) was 1.52 (95% confidence interval [CI] 1.05-2.20) with a number needed to treat of 6.45 (95% CI 2.80-64.80). There is substantial heterogeneity and a slight risk of a publication bias.
CONCLUSIONS AND CLINICAL IMPLICATIONS
There is limited evidence to suggest that vaccinations are effective at reducing UTI recurrence in adult female patients in the short term. Owing to low quality of evidence, the literature requires further long-term RCTs with large sample sizes utilising standardised definitions for conclusive evidence of the long-term efficacy of vaccination in rUTI prevention.
PATIENT SUMMARY
We explored whether vaccines could help stop urinary tract infections (UTIs) from happening again. The latest information shows that these vaccines are safe and may help lower the chances of women getting UTIs again for about 6-12 mo.
PubMed: 38644097
DOI: 10.1016/j.euf.2024.04.002 -
BMJ Evidence-based Medicine Apr 2024To compare the efficacy of influenza vaccines of any valency for adults 60 years and older.
OBJECTIVES
To compare the efficacy of influenza vaccines of any valency for adults 60 years and older.
DESIGN AND SETTING
Systematic review with network meta-analysis (NMA) of randomised controlled trials (RCTs). MEDLINE, EMBASE, JBI Evidence-Based Practice (EBP) Database, PsycINFO, and Cochrane Evidence -Based Medicine database were searched from inception to 20 June 20, 2022. Two reviewers screened, abstracted, and appraised articles (Cochrane Risk of Bias (ROB) 2.0 tool) independently. We assessed certainty of findings using Confidence in Network Meta-Analysis and Grading of Recommendations, Assessment, Development and Evaluations approaches. We performed random-effects meta-analysis and network meta-analysis (NMA), and estimated odds ratios (ORs) for dichotomous outcomes and incidence rate ratios (IRRs) for count outcomes along with their corresponding 95% confidence intervals (CIs) and prediction intervals.
PARTICIPANTS
Older adults (≥60 years old) receiving an influenza vaccine licensed in Canada or the USA (vs placebo, no vaccine, or any other licensed vaccine), at any dose.
MAIN OUTCOME MEASURES
Laboratory-confirmed influenza (LCI) and influenza-like illness (ILI). Secondary outcomes were the number of vascular adverse events, hospitalisation for acute respiratory infection (ARI) and ILI, inpatient hospitalisation, emergency room (ER) visit for ILI, outpatient visit, and mortality, among others.
RESULTS
We included 41 RCTs and 15 companion reports comprising 8 vaccine types and 206 032 participants. Vaccines may prevent LCI compared with placebo, with high-dose trivalent inactivated influenza vaccine (IIV3-HD) (NMA: 9 RCTs, 52 202 participants, OR 0.23, 95% confidence interval (CI) (0.11 to 0.51), low certainty of evidence) and recombinant influenza vaccine (RIV) (OR 0.25, 95%CI (0.08 to 0.73), low certainty of evidence) among the most efficacious vaccines. Standard dose trivalent IIV3 (IIV3-SD) may prevent ILI compared with placebo, but the result was imprecise (meta-analysis: 2 RCTs, 854 participants, OR 0.39, 95%CI (0.15 to 1.02), low certainty of evidence). Any HD was associated with prevention of ILI compared with placebo (NMA: 9 RCTs, 65 658 participants, OR 0.38, 95%CI (0.15 to 0.93)). Adjuvanted quadrivalent IIV (IIV4-Adj) may be associated with the least vascular adverse events, but the results were very uncertain (NMA: eight 8 RCTs, 57 677 participants, IRR 0.18, 95%CI (0.07 to 0.43), very low certainty of evidence). RIV on all-cause mortality may be comparable to placebo (NMA: 20 RCTs, 140 577 participants, OR 1.01, 95%CI (0.23 to 4.49), low certainty of evidence).
CONCLUSIONS
This systematic review demonstrated efficacy associated with IIV3-HD and RIV vaccines in protecting older persons against LCI. RIV vaccine may reduce all-cause mortality when compared with other vaccines, but the evidence is uncertain. Differences in efficacy between influenza vaccines remain uncertain with very low to moderate certainty of evidence.
PROSPERO REGISTRATION NUMBER
CRD42020177357.
PubMed: 38604619
DOI: 10.1136/bmjebm-2023-112767 -
Human Vaccines & Immunotherapeutics Dec 2024Insect vector-borne diseases (VBDs) pose significant global health challenges, particularly in tropical and subtropical regions. The WHO has launched the "Global Vector...
Insect vector-borne diseases (VBDs) pose significant global health challenges, particularly in tropical and subtropical regions. The WHO has launched the "Global Vector Control Response (GVCR) 2017-2030" to address these diseases, emphasizing a comprehensive approach to vector control. This systematic review investigates the potential of malaria and dengue vaccines in controlling mosquito-borne VBDs, aiming to alleviate disease burdens and enhance public health. Following PRISMA 2020 guidelines, the review incorporated 39 new studies out of 934 identified records. It encompasses various studies assessing malaria and dengue vaccines, emphasizing the significance of vaccination as a preventive measure. The findings indicate variations in vaccine efficacy, duration of protection, and safety considerations for each disease, influencing public health strategies. The review underscores the urgent need for vaccines to combat the increasing burden of VBDs like malaria and dengue, advocating for ongoing research and investment in vaccine development.
Topics: Animals; Dengue; Dengue Vaccines; Malaria; Mosquito-Borne Diseases; Public Health; Humans
PubMed: 38602074
DOI: 10.1080/21645515.2024.2337985