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Cancer Prevention Research... Oct 2023Therapeutic targeting of RAS-mutated cancers is difficult, whereas prevention or interception (treatment before or in the presence of preinvasive lesions) preclinically...
Therapeutic targeting of RAS-mutated cancers is difficult, whereas prevention or interception (treatment before or in the presence of preinvasive lesions) preclinically has proven easier. In the A/J mouse lung model, where different carcinogens induce tumors with different KRAS mutations, glucocorticoids and retinoid X receptor (RXR) agonists are effective agents in prevention and interception studies, irrespective of specific KRAS mutations. In rat azoxymethane-induced colon tumors (45% KRAS mutations), cyclooxygenase 1/2 inhibitors and difluoromethylornithine are effective in preventing or intercepting KRAS-mutated or wild-type tumors. In two KRAS-mutant pancreatic models multiple COX 1/2 inhibitors are effective. Furthermore, combining a COX and an EGFR inhibitor prevented the development of virtually all pancreatic tumors in transgenic mice. In the N-nitroso-N-methylurea-induced estrogen receptor-positive rat breast model (50% HRAS mutations) various selective estrogen receptor modulators, aromatase inhibitors, EGFR inhibitors, and RXR agonists are profoundly effective in prevention and interception of tumors with wild-type or mutant HRAS, while the farnesyltransferase inhibitor tipifarnib preferentially inhibits HRAS-mutant breast tumors. Thus, many agents not known to specifically inhibit the RAS pathway, are effective in an organ specific manner in preventing or intercepting RAS-mutated tumors. Finally, we discuss an alternative prevention and interception approach, employing vaccines to target KRAS.
Topics: Mice; Rats; Animals; Proto-Oncogene Proteins p21(ras); Mice, Transgenic; Mutation; Pancreatic Neoplasms; ErbB Receptors; Vaccines; Primary Prevention
PubMed: 37468135
DOI: 10.1158/1940-6207.CAPR-23-0027 -
European Journal of Preventive... Nov 2023
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Cardiovascular Diseases; Hypertension; Diabetes Mellitus; Primary Prevention; Primary Health Care
PubMed: 37439146
DOI: 10.1093/eurjpc/zwad231 -
Obesity Reviews : An Official Journal... Jan 2024Primary prevention targets development of overweight in individuals with healthy weight and is a great challenge. This paper summarizes the main findings of a working... (Review)
Review
A literature review of evidence for primary prevention of overweight and obesity in healthy weight children and adolescents: A report produced by a working group of the Danish Council on Health and Disease Prevention.
Primary prevention targets development of overweight in individuals with healthy weight and is a great challenge. This paper summarizes the main findings of a working group of the Danish Council on Health and Disease Prevention that reviewed the literature on primary prevention of overweight and obesity among children and adolescents. The results were presented in a Danish report, in which a 2019 Cochrane review on childhood obesity prevention was complemented by searches in PubMed to include all relevant subsequent studies published from January 2018 until March 2020. In this paper, the review was updated until June 2023. Numerous childhood overweight prevention interventions have been developed during the past decades, primarily targeting diet and/or physical activity. Several of these interventions showed positive effects on diet and physical activity level but did not show effects on risk of developing overweight. The evidence foundation is inconsistent as four out of five interventions did not show positive effects. Previously observed intervention effects may not reflect excessive weight gain prevention among children with healthy weight but rather bodyweight reduction among those with overweight or obesity. We do not have sufficient knowledge about how to prevent children with healthy weight from developing overweight, and creative solutions are urgently needed.
Topics: Child; Adolescent; Humans; Overweight; Pediatric Obesity; Diet; Denmark; Primary Prevention
PubMed: 37871966
DOI: 10.1111/obr.13641 -
Circulation Jul 2023Black Americans have a higher risk of nonischemic cardiomyopathy (NICM) than White Americans. We aimed to evaluate differences in the risk of tachyarrhythmias among...
BACKGROUND
Black Americans have a higher risk of nonischemic cardiomyopathy (NICM) than White Americans. We aimed to evaluate differences in the risk of tachyarrhythmias among patients with an implantable cardioverter-defibrillator (ICD).
METHODS
The study population comprised 3895 ICD recipients in the United States enrolled in primary prevention ICD trials. Outcome measures included ventricular tachyarrhythmia (VTA), atrial tachyarrhythmia (ATA), ICD therapies, VTA burden (using Andersen-Gill recurrent event analysis), death, and the predicted benefit of the ICD. All events were adjudicated blindly. Outcomes were compared between self-reported Black patients versus White patients with cardiomyopathy (ischemic and NICM).
RESULTS
Black patients were more likely to be female (35% versus 22%) and younger (57±12 versus 62±12 years) with a higher frequency of comorbidities. In NICM, Black patients had a higher rate of first VTA, fast VTA, ATA, and appropriate and inappropriate ICD therapy (VTA ≥170 bpm, 32% versus 20%; VTA ≥200 bpm, 22% versus 14%; ATA, 25% versus 12%; appropriate therapy, 30% versus 20%; and inappropriate therapy, 25% versus 11%; <0.001 for all). Multivariable analysis showed that Black patients with NICM experienced a higher risk of all types of arrhythmia or ICD therapy (VTA ≥170 bpm, hazard ratio [HR] 1.71; VTA ≥200 bpm, HR 1.58; ATA, HR 1.87; appropriate therapy, HR 1.62; inappropriate therapy, HR 1.86; ≤0.01 for all), higher burden of tachyarrhythmias or therapies (VTA, HR 1.84; appropriate therapy, HR 1.84; <0.001 for both), and a higher risk of death (HR 1.92; =0.014). In contrast, in ischemic cardiomyopathy, the risk of all types of tachyarrhythmia, ICD therapy, or death was similar between Black patients and White patients. Both Black patients and White patients derived a significant and similar benefit from ICD implantation.
CONCLUSIONS
Among patients with NICM with an ICD for primary prevention, Black patients compared with White patients had a high risk and burden of VTA, ATA, and ICD therapies with a lower survival rate. Nevertheless, the overall benefit of the ICD was maintained and was similar to that of White patients.
Topics: Humans; Female; United States; Male; White; Death, Sudden, Cardiac; Risk Factors; Arrhythmias, Cardiac; Cardiomyopathies; Defibrillators, Implantable; Tachycardia, Ventricular; Primary Prevention
PubMed: 37459413
DOI: 10.1161/CIRCULATIONAHA.123.065367 -
BMJ Global Health Oct 2023Primary prevention of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) encompasses the timely diagnosis and adequate treatment of the superficial group A... (Review)
Review
Research opportunities for the primary prevention and management of acute rheumatic fever and rheumatic heart disease: a National Heart, Lung, and Blood Institute workshop report.
Primary prevention of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) encompasses the timely diagnosis and adequate treatment of the superficial group A (GAS) infections pharyngitis and impetigo. GAS is the only known inciting agent in the pathophysiology of the disease. However, sufficient evidence indicates that the uptake and delivery of primary prevention approaches in RHD-endemic regions are significantly suboptimal. This report presents expert deliberations on priority research and implementation opportunities for primary prevention of ARF/RHD that were developed as part of a workshop convened by the US National Heart, Lung, and Blood Institute in November 2021. The opportunities identified by the Primary Prevention Working Group encompass epidemiological, laboratory, clinical, implementation and dissemination research domains and are anchored on five pillars including: (A) to gain a better understanding of superficial GAS infection epidemiology to guide programmes and policies; (B) to improve diagnosis of superficial GAS infections in RHD endemic settings; (C) to develop scalable and sustainable models for delivery of primary prevention; (D) to understand potential downstream effects of the scale-up of primary prevention and (E) to develop and conduct economic evaluations of primary prevention strategies in RHD endemic settings. In view of the multisectoral stakeholders in primary prevention strategies, we emphasise the need for community co-design and government engagement, especially in the implementation and dissemination research arena. We present these opportunities as a reference point for research organisations and sponsors who aim to contribute to the increasing momentum towards the global control and prevention of RHD.
Topics: Humans; National Heart, Lung, and Blood Institute (U.S.); Primary Prevention; Rheumatic Fever; Rheumatic Heart Disease; United States
PubMed: 37914184
DOI: 10.1136/bmjgh-2023-012356 -
BMC Endocrine Disorders Sep 2023Concerning ascending trend in the prevalence of chronic type II diabetes, prevention and the development of an effective approach after the recognition of at-risk... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Concerning ascending trend in the prevalence of chronic type II diabetes, prevention and the development of an effective approach after the recognition of at-risk individuals is crucial. This study aims to investigate comparing the influence of lifestyle modification and metformin interventions in the prevention of type II diabetes developments.
METHOD
The search was conducted using PubMed, Google Scholar, Scopus and Web of Science databases. The inclusion criteria include randomized controlled trials (RCT) which studied both lifestyle modification and metformin interventions in the population above 18 years old without a history of any type of diabetes. After excluding studies with intervention time of fewer than 6 months, a systematic review and meta-analysis were performed to evaluate relative risk (RR) with a confidence interval (CI) of 95% of type II diabetes development.
RESULTS
Data from 5 studies were included in the meta-analysis. The population also consists of individuals with a mean age of 50 years old with BMI and FBS of 35.5 and 104.7 mg/dl respectively. Participants range of prevention years was between 2-3 years with a mean of 2.8 years. Lifestyle modification decreases the probability of the incidence of type II diabetes by 25.3% (RR: 0.747, 95% CI, 0.6-0.92) compared to the metformin intervention (p-value = 0.007). Our results indicate that long-term lifestyle modifications can prevent diabetes type II and decrease diabetes mellitus incidence down to one-quarter in comparison to metformin.
CONCLUSION
Lifestyle modification can be more efficacious than metformin in diminishing the incidence of type II diabetes. Therefore, lifestyle modification can be a therapeutic strategy for controlling type II diabetes incidence, especially in high-risk individuals.
Topics: Humans; Middle Aged; Adolescent; Metformin; Diabetes Mellitus, Type 2; Behavior Therapy; Life Style; Primary Prevention
PubMed: 37723440
DOI: 10.1186/s12902-023-01445-9 -
Journal of the American Geriatrics... Feb 2024
Topics: Humans; Aged; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Cardiovascular Diseases; Risk Factors; Primary Prevention
PubMed: 38217414
DOI: 10.1111/jgs.18764 -
Cancer Journal (Sudbury, Mass.)Cancer continues to be the second most common cause of death in the United States. Racially and ethnically minoritized populations continue to experience disparities in...
Cancer continues to be the second most common cause of death in the United States. Racially and ethnically minoritized populations continue to experience disparities in cancer prevention compared with majority populations. Multilevel interventions-from policy, communities, health care institutions, clinical teams, families, and individuals-may be uniquely suited to reducing health disparities through behavioral risk factor modification in these populations. The aim of this article is to provide a brief overview of the evidence for primary prevention among racially and ethnically minoritized subpopulations in the United States. We focus on the epidemiology of tobacco use, obesity, diet and physical activity, alcohol use, sun exposure, and smoking, as well as increasing uptake of the Human Papillomavirus Vaccine (HPV), as mutable behavioral risk factors. We describe interventions at the policy level, including raising excise taxes on tobacco products; within communities and with community partners, for safe greenways and parks, and local healthful food; health care institutions, with reminder systems for HPV vaccinations; among clinicians, by screening for alcohol use and providing tailored weight reduction approaches; families, with HPV education; and among individuals, routinely using sun protection. A multilevel approach to primary prevention of cancer can modify many of the risk factors in racially and ethnically minoritized populations for whom cancer is already a burden.
Topics: Humans; United States; Papillomavirus Infections; Risk Factors; Neoplasms; Smoking; Primary Prevention
PubMed: 37963370
DOI: 10.1097/PPO.0000000000000686 -
Human Vaccines & Immunotherapeutics Aug 2023Conflict poses a threat to the stability of health-care systems around the world. Within the context of immunization service delivery, conflict-affected geographies are... (Review)
Review
Conflict poses a threat to the stability of health-care systems around the world. Within the context of immunization service delivery, conflict-affected geographies are often dogged by recurrent disease outbreaks due to the inability to administer life-saving vaccines to children residing in these areas. Essential immunization coverage is often poor in conflict-affected geographies, and within the specific context of the Global Polio Eradication Initiative (GPEI), multiple rounds of supplementary immunization activities are often needed to compensate for the inability to provide adequate immunization services. In order to implement polio vaccination activities, GPEI has often resorted to innovative approaches to reach and vaccinate children in security-compromised areas. This article examines the approaches adopted by the global polio program in conducting vaccination activities in conflict-affected geographies with the aim of understanding how they have influenced the successes and setbacks of the program in its bid to eradicate all polioviruses.
Topics: Child; Humans; Animals; Dogs; Vaccination; Immunization; Behavior Therapy; Vaccination Coverage; Poliomyelitis
PubMed: 37489591
DOI: 10.1080/21645515.2023.2237390 -
European Journal of Preventive... Nov 2023Obesity is a prevalent chronic disorder and a well-known risk factor for cardiovascular disease. However, the evidence of treating obesity for primary prevention of... (Meta-Analysis)
Meta-Analysis Review
Obesity is a prevalent chronic disorder and a well-known risk factor for cardiovascular disease. However, the evidence of treating obesity for primary prevention of major cardiovascular events is still scarce and controversial. In this review, we provided a comprehensive description of the current evidence in treating obesity regarding cardiovascular protection. Bariatric surgery appears to be the most robust method to reduce events in people without established cardiovascular disease. High compliance to lifestyle interventions can further reduce cardiovascular risk. Concerning pharmacological therapies, a post hoc analysis from SUSTAIN-6 and a meta-analysis from STEP trials suggest that semaglutide, a GLP-1 receptor agonist, could reduce cardiovascular events in people without established cardiovascular disease. The first study addressed specifically a high-risk population with diabetes and, the second, low- or intermediary-risk individuals without diabetes. Tirzepatide, a novel dual GIP/GLP-1 agonist, although not yet tested in specific cardiovascular outcomes trials, could be an alternative since it induces loss in weight similar to the achieved by bariatric surgery. Therefore, extrapolated data in distinct baseline cardiovascular risk populations suggest that these two drugs could be used in primary prevention with the aim of preventing cardiovascular events, but the grade of this evidence is still low. Specifically designed studies are needed to address this specific topic.
Topics: Humans; Cardiovascular Diseases; Obesity; Glucagon-Like Peptide 1; Diabetes Mellitus; Primary Prevention; Diabetes Mellitus, Type 2; Hypoglycemic Agents
PubMed: 37648659
DOI: 10.1093/eurjpc/zwad280