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Vaccines Jul 2023As the world continues to urbanize, particularly in low- and middle-income countries, understanding the barriers and effective interventions to improve urban... (Review)
Review
INTRODUCTION
As the world continues to urbanize, particularly in low- and middle-income countries, understanding the barriers and effective interventions to improve urban immunization equity is critical to achieving both Immunization Agenda 2030 targets and the Sustainable Development Goals. Approximately 25 million children missed one or more doses of the diphtheria, tetanus and pertussis (DTP3) vaccine in 2021 and it is estimated that close to 30% of the world's children missing the first dose of DTP, known as zero-dose, live in urban and peri-urban settings.
METHODS
The aim of this research is to improve understanding of urban immunization equity through a qualitative review of mixed method studies, urban immunization strategies and funding proposals across more than 70 urban areas developed between 2016 and 2020, supported by Gavi, the Vaccine Alliance. These research studies and strategies created a body of evidence regarding the barriers to vaccination in urban settings and potential interventions relevant to low- and middle-income countries (LMICs) with a focus on the vaccination of urban poor, populations of concern and residents of informal settlements. Through the document review we identified common challenges to achieving equitable coverage in urban areas and mapped proposed interventions.
RESULTS
We identified 70 documents as part of the review and categorized results across (1) social determinants of health, (2) immunization service-delivery barriers and (3) quality of services. Barriers and solutions identified in the documents were categorized in these thematic areas, drawing information from results in more than 21 countries.
CONCLUSION
Populations of concern such as migrants, refugees, residents of informal settlements and the urban poor face barriers to accessing care which include poor availability and quality of service. Example solutions proposed to these challenges include tailored delivery strategies, improved use of digital data collection and child-friendly services. More research is required on the efficacy of the proposed interventions identified and on gender-specific dynamics in urban poor areas affecting equitable immunization coverage.
PubMed: 37515016
DOI: 10.3390/vaccines11071200 -
Infectious Diseases and Therapy Nov 2023Pertussis, caused by Bordetella pertussis, remains one of the most widespread, contagious, and vaccine-preventable diseases. It results in notable morbidity and... (Review)
Review
Pertussis, caused by Bordetella pertussis, remains one of the most widespread, contagious, and vaccine-preventable diseases. It results in notable morbidity and mortality as well as severe medical, social, and economic burden. Despite high global vaccine coverage, pertussis continues to be a significant epidemiologic problem, with outbreak episodes every few years just as in the pre-vaccination era. In Türkiye, there is a lack of comprehensive data on the current burden of pertussis in different age and risk groups, leading to underdiagnosis and underreporting of the disease, especially in adults who are often not considered at risk. Available data from Türkiye also reveal inadequate levels of protective antibodies in preterm newborns, emphasizing the need for additional preventive measures. Authors stated that improving physician awareness of pertussis symptoms in patients with prolonged cough, increasing access to routine pertussis tests, and conducting surveillance studies would aid in accurate diagnosis and reporting in Türkiye. As the Turkish Ministry of Health Antenatal Care Management Guide suggests routine second and third pregnancy check-up visits at weeks 18-24 and 28-32 correspondingly, this period can be considered the ideal vaccination time for Türkiye. Introducing a booster dose of Tdap at around 10 years of age or during national military service would reduce transmission and protect susceptible individuals. Identifying individuals at high risk of severe pertussis and prioritizing them for a booster dose is also crucial in Türkiye. Enhancing surveillance systems, increasing healthcare professionals' awareness through training, and organizing catch-up visits for missed vaccinations during the COVID-19 pandemic are mentioned as additional strategies to improve pertussis prevention in Türkiye. This review focuses on the global and regional burden of pertussis and obstacles to effective prevention and evaluates existing strategies to achieve lifelong pertussis prevention. Literature and current strategies were also discussed from a Turkish national standpoint.
PubMed: 37815753
DOI: 10.1007/s40121-023-00876-0 -
Supportive Care in Cancer : Official... Jan 2024Despite the availability of various prevention methods, dental caries continue to be diagnosed in patients receiving head and neck radiotherapy (RT). Since conventional...
PURPOSE
Despite the availability of various prevention methods, dental caries continue to be diagnosed in patients receiving head and neck radiotherapy (RT). Since conventional approaches do not evaluate posttreatment alterations in dietary behaviors, we aimed to assess the influence of radiation-induced xerostomia on post-RT cariogenic dietary habits in patients.
METHODS
Fifty-seven patients completed the Xerostomia Questionnaire (XQ) and answered questions regarding daily cariogenic food and beverage (CFB) intake, daily tooth brushing, fluoride application, and subjective total taste acuity (STTA). They also underwent evaluations to determine the Simplified Oral Hygiene Index (OHI-S) score, Saxon test score, number of decayed-missing-filled teeth (DMFT), and proportion of DMFT to the test teeth (DMFT rate). Clinical records were searched for information regarding RT modalities, including the median of the mean dose to the parotid glands, days after the completion of RT, submandibular gland resection, whole-neck irradiation, and the DMFT value and rate before RT. The patients were divided into low and high XQ score groups based on the median XQ score of 47.5 for the two sample tests. Univariable and multivariable regression analyses were used to identify independent factors for frequent CFB intake.
RESULTS
Higher XQ scores were associated with a significantly greater frequency of CFB intake (p = 0.028*). Regression analysis also identified a higher XQ score (p = 0.017*) as an independent risk factor for frequent CFB intake.
CONCLUSION
Radiation-induced xerostomia increased the frequency of CFB intake.
Topics: Humans; Dental Caries; Xerostomia; Oral Ulcer; Feeding Behavior; Radiation Oncology
PubMed: 38193941
DOI: 10.1007/s00520-023-08298-x -
Frontiers in Toxicology 2023While targeted investigation of key toxicity pathways has been instrumental for biomarker discovery, unbiased and holistic analysis of transcriptomic data provides a...
While targeted investigation of key toxicity pathways has been instrumental for biomarker discovery, unbiased and holistic analysis of transcriptomic data provides a complementary systems-level perspective. However, in a systematic context, this approach has yet to receive comprehensive and methodical implementation. Here, we took an integrated bioinformatic approach by re-analyzing publicly available MCF7 cell TempO-seq data for 44 ToxCast chemicals using an alternative pipeline to demonstrate the power of this approach. The original study has focused on analyzing the gene signature approach and comparing them to biological pathway altering concentrations determined from ToxCast HTS assays. Our workflow, in comparison, involves sequential differential expression, gene set enrichment, benchmark dose modeling, and identification of commonly perturbed pathways by network visualization. Using this approach, we identified dose-responsive molecular changes, biological pathways, and points of departure in an untargeted manner. Critically, benchmark dose modeling based on pathways recapitulated points of departure for apical endpoints, while also revealing additional perturbed mechanisms missed by single endpoint analyses. This systems-toxicology approach provides multifaceted insights into the complex effects of chemical exposures. Our work highlights the importance of unbiased data-driven techniques, alongside targeted methods, for comprehensively evaluating molecular initiating events, dose-response relationships, and toxicity pathways. Overall, integrating omics assays with robust bioinformatics holds promise for improving chemical risk assessment and advancing new approach methodologies (NAMs).
PubMed: 38046401
DOI: 10.3389/ftox.2023.1272364 -
Diabetes Technology & Therapeutics Jan 2024Connected insulin pens are creating opportunities for the millions of individuals with diabetes using multiple daily injections (MDI) therapy across the globe....
Connected insulin pens are creating opportunities for the millions of individuals with diabetes using multiple daily injections (MDI) therapy across the globe. Continuous glucose monitoring (CGM) data from connected insulin pens are revealing gaps and opportunities to significantly improve care for this population. In this article, we report real-world findings of the InPen™ smart insulin pen paired with CGM (InPen system), used by persons with type 1 diabetes (T1D) and type 2 diabetes (T2D). A retrospective cohort analysis was conducted with the real-world data collected from the InPen system of individuals ( = 3793 with T1D, = 552 with T2D, and = 808 unidentified) who used the system from January 01, 2020, to December 31, 2021. Diabetes management (e.g., missed and mistimed insulin dosing, mismatched food intake, and correction dose delivery) and glycemic outcomes were assessed. In the overall and T1D populations, a dosing frequency of ≥3 doses per day and a missed dose frequency of <20% was associated with improved glycemia. In adults with T2D, missing <20% of doses was the significant factor determining improved glycemia. This analysis, integrating data from a smart insulin pen and CGM, provides insights into the impact of dosing behavior on glycemic outcomes and informs counseling strategies for the diabetes care team, through technologically advanced insulin management for those using MDI therapy.
Topics: Adult; Humans; Insulin; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Blood Glucose Self-Monitoring; Retrospective Studies; Blood Glucose; Insulin, Regular, Human
PubMed: 37855818
DOI: 10.1089/dia.2023.0365 -
Vaccines Dec 2023The WHO recommended the use of the RTS,S/AS01 malaria vaccine (RTS,S) based on a pilot evaluation in routine use in Ghana, Kenya, and Malawi. A longitudinal qualitative...
Acceptance of and Adherence to a Four-Dose RTS,S/AS01 Schedule: Findings from a Longitudinal Qualitative Evaluation Study for the Malaria Vaccine Implementation Programme.
BACKGROUND
The WHO recommended the use of the RTS,S/AS01 malaria vaccine (RTS,S) based on a pilot evaluation in routine use in Ghana, Kenya, and Malawi. A longitudinal qualitative study was conducted to examine facilitators and barriers to uptake of a 4-dose RTS,S schedule.
METHODS
A cohort of 198 caregivers of RTS,S-eligible children from communities where RTS,S was provided through the pilot were interviewed three times over a ≈22-month, 4-dose schedule. The interviews examined caregiver perceptions and behaviors. Children's vaccination history was obtained to determine dose uptake.
RESULTS
162 caregivers remained at round 3 (R3); vaccination history was available for 152/162 children. Despite early rumors/fears, the uptake of initial doses was high, driven by vaccine trust. Fears dissipated by R2, replaced with an enthusiasm for RTS,S as caregivers perceived its safety and less frequent and severe malaria. By R3, 98/152 children had received four doses; 34 three doses; 9 one or two doses; and 11 zero doses. The health system and information barriers were important across all under-dose cases. Fears about AEFIs/safety were important in zero-, one-, and two-dose cases. Competing life/livelihood demands and complacency were found in three-dose cases. Regardless of the doses received, caregivers had positive attitudes towards RTS,S by R3.
CONCLUSIONS
Findings from our study will help countries newly introducing the vaccine to anticipate and preempt reasons for delayed acceptance and missed RTS,S doses.
PubMed: 38140205
DOI: 10.3390/vaccines11121801 -
Biomedicines Nov 2023Acute respiratory distress syndrome (ARDS) is often a consequence of a dysregulated immune response; therefore, immunomodulation by extracorporeal cytokine removal has... (Review)
Review
BACKGROUND
Acute respiratory distress syndrome (ARDS) is often a consequence of a dysregulated immune response; therefore, immunomodulation by extracorporeal cytokine removal has been increasingly used as an adjuvant therapy, but convincing data are still missing. The aim of this study was to investigate the effects of adjunctive hemoadsorption (HA) on clinical and laboratory outcomes in patients with ARDS.
METHODS
We performed a systematic literature search in PubMed, Embase, CENTRAL, Scopus, and Web of Science (PROSPERO: CRD42022292176). The population was patients receiving HA therapy for ARDS. The primary outcome was the change in PaO2/FiO2 before and after HA therapy. Secondary outcomes included the before and after values for C-reactive protein (CRP), lactate, interleukin-6 (IL-6), and norepinephrine (NE) doses.
RESULTS
We included 26 publications, with 243 patients (198 undergoing HA therapy and 45 controls). There was a significant improvement in PaO2/FiO2 ratio following HA therapy (MD = 68.93 [95%-CI: 28.79 to 109.06] mmHg, = 0.005) and a reduction in CRP levels (MD = -45.02 [95%-CI: -82.64; -7.39] mg/dL, = 0.026) and NE dose (MD = -0.24 [95%-CI: -0.44 to -0.04] μg/kg/min, = 0.028).
CONCLUSIONS
Based on our findings, HA resulted in a significant improvement in oxygenation and a reduction in NE dose and CRP levels in patients treated with ARDS. Properly designed RCTs are still needed.
PubMed: 38002070
DOI: 10.3390/biomedicines11113068 -
Lipids in Health and Disease May 2024Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) exhibit potential as therapeutics for a variety of diseases. This observational and Mendelian randomization (MR)... (Observational Study)
Observational Study
BACKGROUND
Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) exhibit potential as therapeutics for a variety of diseases. This observational and Mendelian randomization (MR) study aims to explore the relationship between omega-3 PUFAs and osteoarthritis (OA).
METHODS
Excluding individuals under 20 years old and those with missing data on relevant variables in the National Health and Nutrition Examination Survey (NHANES) spanning from 2003 to 2016, a total of 22 834 participants were included in this cross-sectional study. Weighted multivariable-adjusted logistic regression was used to estimate the association between omega-3 PUFAs and OA in adults. Moreover, restricted cubic splines were utilized to examine the dose-response relationship between omega-3 PUFAs and OA. To further investigate the potential causal relationship between omega-3 PUFAs and OA risk, a two-sample MR study was conducted. Furthermore, the robustness of the findings was assessed using various methods.
RESULTS
Omega-3 PUFAs intake were inversely associated with OA in adults aged 40 ∼ 59 after multivariable adjustment [Formula: see text], with a nonlinear relationship observed between omega-3 PUFAs intake and OA [Formula: see text]. The IVW results showed there was no evidence to suggest a causal relationship between omega-3 PUFAs and OA risk [Formula: see text].
CONCLUSIONS
Omega-3 PUFAs were inversely associated with OA in adults aged 40 ∼ 59. However, MR studies did not confirm a causal relationship between the two.
Topics: Humans; Osteoarthritis; Fatty Acids, Omega-3; Mendelian Randomization Analysis; Male; Middle Aged; Female; Adult; Nutrition Surveys; Cross-Sectional Studies; Risk Factors
PubMed: 38760818
DOI: 10.1186/s12944-024-02139-4 -
Heart and Vessels Sep 2023The outcome of the patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) is also influenced by the renal and hepatic organ functions. Risk...
The outcome of the patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) is also influenced by the renal and hepatic organ functions. Risk stratification, using scores such as EURO Score II or STS Short-Term Risk Calculator for patients undergoing cardiac surgery with cardiopulmonary bypass, ignores the quantitative renal and hepatic function; therefore, MELD-Score was applied in these cases. We retrospectively examined patient data using the MELD score as a predictor of mortality. To perform a univariate analysis of the data, patients were classified into three groups based on the MELD Score: MELD < 10 (Group 1), MELD 10 to 19 (Group 2), and MELD ≥ 20 (Group 3). A total of 11,477 participants were included in the study, though several patients with either missing MELD scores or lack of creatinine, bilirubin, or INR levels were dropped from the original cohort. Eventually, 10,882 patients were included in the analysis. The primary outcome was defined as postoperative, in-hospital mortality. Secondary outcomes such as postoperative bleeding, including the requirement for repeat thoracotomy, postoperative neurological complications, and assessment of catecholamines on weaning from cardiopulmonary bypass/ requirement of mechanical circulatory support were examined. A higher MELD score was associated with increased postoperative mortality. Patients with MELD > 20 experienced a 31.2% postoperative mortality, compared to Group 1 (4.6%) and Group 2 (17.5%). The highest rates of postoperative bleeding (13.8%) and, repeat thoracotomy (13.2%) & postoperative pneumonia (17.4%) were seen in Group 3 (threefold increase when compared to Group 1, renal failure requiring dialysis (N = 235, 2.7% in Group 1 v/s N = 78, 22.9% in Group 3) or requiring high dose catecholamines post-operatively or mechanical circulatory support (IABP/ECLS). Incidentally, an increased MELD Score was not associated with a significant increase in the postoperative incidence of stroke/TIA or the presence of sternal wound infections/complications. A higher mortality was observed in patients with reduced liver and renal function, with a significant increase in patients with a MELD score > 20. As the current risk stratification scores do not consider this, we recommend applying the MELD score before considering patients for cardiac surgery.
Topics: Humans; Retrospective Studies; Cardiac Surgical Procedures; Risk Factors; Postoperative Complications; Liver; Risk Assessment
PubMed: 37004541
DOI: 10.1007/s00380-023-02262-9 -
European Journal of Cancer (Oxford,... Aug 2023The pharmaceutical industry's productivity has been declining over the last two decades and high attrition rates and reduced regulatory approvals are being seen. The...
BACKGROUND
The pharmaceutical industry's productivity has been declining over the last two decades and high attrition rates and reduced regulatory approvals are being seen. The development of oncology drugs is particularly challenging with low rates of approval for novel treatments when compared with other therapeutic areas. Reliably establishing the potential of novel treatment and the corresponding optimal dosage is a key component to ensure efficient overall development. A growing interest lies in terminating developments of poor treatments quickly while enabling accelerated development for highly promising interventions.
METHODS
One approach to reliably establish the optimal dosage and the potential of a novel treatment and thereby improve efficiency in the drug development pathway is the use of novel statistical designs that make efficient use of the data collected.
RESULTS
In this paper, we discuss different (seamless) strategies for early oncology development and illustrate their strengths and weaknesses through real trial examples. We provide some directions for good practices in early oncology development, discuss frequently seen missed opportunities for improved efficiency and some future opportunities that have yet to fully develop their potential in early oncology treatment development.
DISCUSSION
Modern methods for dose-finding have the potential to shorten and improve dose-finding and only small changes to current approaches are required to realise this potential.
Topics: Humans; Medical Oncology; Drug Development; Research Design; Neoplasms
PubMed: 37301716
DOI: 10.1016/j.ejca.2023.05.005