Long-term Preventive Effects Research Articles

Cost-effectiveness of allergen immunotherapy.

Allergic rhinitis is a relevant and global health problem affecting up to 5-50% of the general population and its prevalence is increasing due to climate change and pollution among other factors and counts among the 10 most frequent reasons for medical consultation, generating an important economic impact. Allergen immunotherapy (AIT) is the only allergy-disease-modifying treatment and there is plenty of evidence of its effectiveness with regards subcutaneous and oral routes of AIT.This narrative review article examines published literature in the last 24 months regarding the pharmacoeconomics of AIT versus standard of care treatment (SOC) for the treatment of allergic rhinitis and asthma. Farraia et al. assessed in 2022 subcutaneous immunotherapy (SCIT, _438/$500.28) and sublingual immunotherapy (SLIT) (_1021/$1116.19) plus symptomatic treatment versus SOC treatment in children with HDM-driven allergic asthma, measuring QALYs, decrease of medication, decrease of exacerbations and symptoms. They used the cost-effective threshold: _18 482.80 ($21 110.14), finding that AIT is cost-effective.Also, SCIT and SLIT plus symptomatic treatment was assessed versus SOC treatment in children with grass pollen allergic rhinitis. The authors concluded that SCIT (_933/$1065.67) and SLIT (_1408/ $1608.22) seem cost-effective, particularly SCIT. Allergen immunotherapy is cost-effective in the management of allergic rhinitis and asthma as compared with SOC alone. As most studies consider only during-treatment costs and no long-term benefits or preventive effects are being assessed, the real cost-effectiveness of allergen immunotherapy could be even higher.

CAR T therapy from haematological malignancies to aging-related diseases: An ever-expanding universe.

Short but impactful, the two-decade story of gene editing allowed a significant breakthrough in the treatment of haematological malignancies. However, despite different generations of chimeric antigen receptor T (CAR T), such a successful therapy has not yet been replicated in solid tumours and non-oncological diseases. This narrative review discusses how CAR T therapy still faces challenges in overcoming the complexity of the solid tumour microenvironment and the concerns that its long-term activity raises about potential unknown and unpredictable consequences in non-oncological diseases. In the most recent studies, the senolytic potential of CAR T is becoming an exciting field of research. Still, experimental but promising results indeed indicate the clearance of senescent cells as an effective strategy to improve exercise capacity and metabolic dysfunction in physiological ageing, with long-term therapeutic and preventive effects. However, an effective expansion of a CAR T population requires a lympho-depleting chemotherapy prior to infusion. While this procedure sounds reasonable for rescue therapy of oncological diseases, it poses genotoxic risks that may not be justified for non-malignant diseases. Those represent the leading gaps for applying CAR T therapy in non-oncological diseases. More is expected from current studies on the other classes of CAR cells now under investigation. Engineering NK cells and macrophages are candidates to improve cytotoxic and immunomodulating properties, potentially able to broaden application in solid tumours and non-oncological diseases. Finally, engineering autologous T cells in old individuals may generate biologically deteriorated CAR T clones with impaired function and unpredictable effects on cytokine release.

Prophylactic and long-lasting efficacy of senolytic CAR T cells against age-related metabolic dysfunction.

Senescent cells, which accumulate in organisms over time, contribute to age-related tissue decline. Genetic ablation of senescent cells can ameliorate various age-related pathologies, including metabolic dysfunction and decreased physical fitness. While small-molecule drugs that eliminate senescent cells ('senolytics') partially replicate these phenotypes, they require continuous administration. We have developed a senolytic therapy based on chimeric antigen receptor (CAR) T cells targeting the senescence-associated protein urokinase plasminogen activator receptor (uPAR), and we previously showed these can safely eliminate senescent cells in young animals. We now show that uPAR-positive senescent cells accumulate during aging and that they can be safely targeted with senolytic CAR T cells. Treatment with anti-uPAR CAR T cells improves exercise capacity in physiological aging, and it ameliorates metabolic dysfunction (for example, improving glucose tolerance) in aged mice and in mice on a high-fat diet. Importantly, a single administration of these senolytic CAR T cells is sufficient to achieve long-term therapeutic and preventive effects.

The mitochondrial genome-encoded peptide MOTS-c interacts with Bcl-2 to alleviate nonalcoholic steatohepatitis progression

Nonalcoholic steatohepatitis (NASH) is a metabolism-associated fatty liver disease with accumulated mitochondrial stress, and targeting mitochondrial function is a potential therapy. The mitochondrial genome-encoded bioactive peptide MOTS-c plays broad physiological roles, but its effectiveness and direct targets in NASH treatment are still unclear. Here, we show that long-term preventive and short-term therapeutic effects of MOTS-c treatments alleviate NASH-diet-induced liver steatosis, cellular apoptosis, inflammation, and fibrosis. Mitochondrial oxidative capacity and metabolites profiling analysis show that MOTS-c significantly reverses NASH-induced mitochondrial metabolic deficiency. Moreover, we identify that MOTS-c directly interacts with the BH3 domain of antiapoptotic B cell lymphoma-2 (Bcl-2), increases Bcl-2 protein stability, and suppresses Bcl-2 ubiquitination. By using a Bcl-2 inhibitor or adeno-associated virus (AAV)-mediated Bcl-2 knockdown, we further confirm that MOTS-c improves NASH-induced mitochondrial dysfunction, inflammation, and fibrosis, which are dependent on Bcl-2 function. Therefore, our findings show that MOTS-c is a potential therapeutic agent to inhibit the progression of NASH.

Carrier-Free Nanovaccine: An Innovative Strategy for Ultrahigh Melanoma Neoantigen Loading.

In personalized cancer immunotherapy, developing an effective neoantigen nanovaccine with high immunogenicity is a significant challenge. Traditional nanovaccine delivery systems often require nanocarriers, which can hinder the delivery of the neoantigen and cause significant toxicity. In this study, we present an innovative strategy of carrier-free nanovaccine achieved through direct self-assembly of 2'-fluorinated CpG (2'F-CpG) with melanoma neoantigen peptide (Obsl1). Molecular dynamics simulations demonstrated that the introduction of a fluorine atom into CpG increases the noncovalent interaction between 2'F-CpG and Obsl1, which enhanced the loading of Obsl1 on 2'F-CpG, resulting in the spontaneous formation of a hybrid 2'F-CpG/Obsl1 nanovaccine. This nanovaccine without extra nanocarriers showed ultrahigh Obsl1 loading up to 83.19 wt %, increasing the neoantigen peptide uptake by antigen-presenting cells (APCs). In C57BL/6 mice models, we demonstrated the long-term preventive and therapeutic effects of the prepared 2'F-CpG/Obsl1 nanovaccine against B16F10 melanoma. Immunocellular analysis revealed that the nanovaccine activated innate and adaptive immune responses to cancer cells. Hence, this study established a simple, safe, and effective preparation strategy for a carrier-free neoantigen nanovaccine, which could be adapted for the future design of personalized cancer vaccines in clinical settings.

Comparison of Long-term Preventive Effects of Dual Antiplatelet Therapy vs. Monotherapy in High Cardiovascular Risk Patients After Myocardial Infarction with Nonobstructive Coronary Arteries (MINOCA)

Comparison of Long-term Preventive Effects of Dual Antiplatelet Therapy vs. Monotherapy in High Cardiovascular Risk Patients After Myocardial Infarction with Nonobstructive Coronary Arteries (MINOCA)

Fewer maternal depression symptoms after the Close Collaboration with Parents intervention: Two-year follow-up.

AimTo test whether the implementation of the Close Collaboration with Parents intervention at a neonatal intensive care unit (NICU) decreases depression symptoms of mothers up to two years after the delivery of preterm infants.MethodsWe used a non‐equivalent two‐group design, comparing mothers of very low birthweight infants in the same NICU before (2001–2006) and after (2011–215) the intervention. The unit carried out the educational intervention (2009–2012) that was targeted at its healthcare team and aimed to improve their skills to collaborate with parents. Maternal depression symptoms were measured using the Edinburgh Postnatal Depression Scale (EPDS) six months and two years after the expected birth date of the infant.ResultsWe found a median difference of 2.56 (95% CI from 1.64 to 3.48) in EPDS at the two‐year follow‐up between the pre‐intervention and post‐intervention groups, p < 0.001. Furthermore, we found no interaction between measurement time‐points and group, implying that the intervention effect on maternal depression symptoms was similar at the six‐month and two‐year time‐points.ConclusionThe intervention seems to have long‐term preventive effects on maternal depressive symptoms. This effect is of clinical significance as prolonged maternal depression associates with adverse child outcomes.

Evaluation of the SPARK Child Mentoring Program: A Social and Emotional Learning Curriculum for Elementary School Students

Social and Emotional Learning (SEL) programs seek to enhance social and emotional competencies in children, including self-awareness, self-management, social awareness, relationship skills, and responsible decision-making. By means of direct instruction regarding social and emotional competencies, SEL programs have the potential to strengthen resilience in children and thus their capacity to effectively cope with life’s challenges. Strengthening resilience in children who are repeatedly exposed to adverse experiences, particularly those from economically disadvantaged minority backgrounds, is of particular importance and has implications for the prevention of a multitude of problems later in life. Our study reports the result of an investigation of the SPARK Child Mentoring program, a resilience-focused SEL program designed to reduce risk factors, uncover innate resilience, promote natural emotional well-being, and facilitate school success. We employed a randomized controlled trial comprising 94 elementary school students that included pre- and post-intervention measurements. After controlling for pre-intervention levels, we found a significant difference between students’ understanding of underlying program principles; communication, decision making, and problem-solving skills; emotional regulation; and resilience for students who received the intervention compared to students who did not receive the intervention. These results provide initial evidence for the efficacy of the SPARK Child Mentoring program with a diverse sample of elementary school students and adds to the existing literature base concerning positive outcomes associated with SEL programs. We discuss implications for future research focused on long-term preventive effects of the program and the characteristics of students most likely to benefit from it.

Prevention of UV-induced skin cancer in mice by gamma oryzanol-loaded nanoethosomes

AimsSkin cancer is the most widespread cancer worldwide, mainly caused by exposure to ultraviolet radiation (UV) in sunlight. Utilizing topical preventive agents in routinely daily used cosmetics may prevent UV-related skin damages and skin cancers. γ-Oryzanol (GO) is a natural component derived from rice bran oil, with potential antioxidant and skin anti-aging properties. Main methodsWe biologically thorough studied the antioxidant and anticancer effects of GO in vitro to found the effective signaling pathways, then evaluated the sun protection factor of prepared formulation, and finally investigated the long-term preventive effects of GO-loaded nanoethosomes (GO-NEs) against UVB-induced skin cancer in mice. Key findingsGO-NEs could effectively prevent UVB-induced skin cancer. SignificanceOur results suggest that GO-NEs could be utilized as an innovative ingredient in cosmetics.

Preventing Recurrence of Depression: Long-Term Effects of a Randomized Controlled Trial on Cognitive Control Training for Remitted Depressed Patients

Previous studies suggest that cognitive control training (CCT) shows potential as a preventive intervention for depression. In this study, the first to examine long-term preventive effects of CCT, we examined effects on (a) task-specific cognitive transfer at 1-year follow-up, (b) recurrence of depression, and (c) functioning over the course of a year. Each of 92 remitted depressed patients were randomly assigned to a CCT condition or an active control condition (ACT). Effects of training were monitored using weekly assessments of emotion regulation, cognitive complaints, depressive symptoms, and resilience (brief weekly questionnaire). At 1-year follow-up, participants completed a structured clinical interview, cognitive transfer task, and questionnaires. We observed task-specific cognitive transfer ( p &lt; .001, d = 1.23) and lower recurrence rates in the CCT condition ( p = .04; odds ratio = 0.38). However, no long-term beneficial effects of training were observed on the weekly ratings of functioning, and groups did not differ in performance on the self-report questionnaires at 1-year follow-up.

Longitudinal effects of a nationwide lifestyle intervention program on cardiometabolic outcomes in Japan: An observational cohort study

The Japanese government launched a nationwide health screening and lifestyle intervention program in 2008 to prevent and reduce metabolic syndrome in at-risk individuals. This study examined the longitudinal effects of the program's lifestyle interventions on metabolic outcomes using health insurance data from one prefecture. The study population comprised 16,317 individuals aged 40–74 years who met the recommendation criteria for the interventions between 2009 and 2015. Participants were categorized into an overall intervention group (comprising a single-session motivational intervention group and a multi-session intensive intervention group) and a non-intervention group. We evaluated the interventions' effects on the initiation of medications for metabolic disorders (hyperlipidemia, hypertension, and hyperglycemia) and metabolic syndrome incidence for 6 years using discrete hazard models that adjusted for sex, age, health screening measurements, and smoking habit. The longitudinal effects on health screening measurements were also evaluated using regression models for repeated measures. The adjusted hazard ratios (aHRs) (95% confidence interval [CI]) for initiation of medications were 0.83 (0.77–0.90), 0.77 (0.71–0.84), and 0.66 (0.57–0.77) for overall, motivational, and intensive interventions, respectively. The aHRs (95%CI) for metabolic syndrome incidence were 0.84 (0.75–0.94), 0.80 (0.71–0.91), and 0.67 (0.51–0.89) for overall, motivational, and intensive interventions, respectively. The interventions reduced body mass index and waist circumference, but had modest effects on blood lipids, blood glucose, and hemoglobin A1c levels; blood pressure was unaffected. These interventions represent an effective strategy to prevent the progression of preclinical metabolic syndrome, but further studies are needed to evaluate their long-term preventive effects on cardiovascular disease and diabetes.

Manual lymph drainage may not have a preventive effect on the development of breast cancer-related lymphoedema in the long term: a randomised trial.

What are the short-term and long-term preventive effects of manual lymph drainage (MLD), when used in addition to information and exercise therapy, on the development of lymphoedema after axillary dissection for breast cancer? Randomised controlled trial with concealed allocation, blinded assessors and intention-to-treat analysis. Adults undergoing unilateral dissection for breast cancer were recruited, with 79 allocated to the experimental group and 81 to the control group. The experimental group received guidelines about prevention of lymphoedema, exercise therapy and MLD. The control group received the same guidelines and exercise therapy, but no MLD. The interventions in both groups were delivered for 6 months. The primary outcome was cumulative incidence of arm lymphoedema defined in four ways (≥200ml,≥2cm,≥5%, and≥10% increase), which represent the difference in arm volume or circumference between the affected and healthy sides compared with the difference before surgery. Secondary outcomes included point prevalence of lymphoedema, change in arm volume difference, shoulder range of movement, quality of life and function. Incidence rates were comparable between experimental and control groups at all follow-up measurements. Sixty months after surgery, the cumulative incidence rate for the≥200ml definition was 35% for the experimental group versus 29% for the control group (RR 0.89, 95% CI 0.51 to 1.54, p=0.45); for the≥2cm definition 35% versus 38% (RR 0.93, 95% CI 0.59 to 1.45, p=0.73); for the≥5% definition 68% versus 53% (RR 1.28, 95% CI 0.97 to 1.69, p=0.08) and for the≥10% definition 28% versus 24% (RR 1.18, 95% CI 0.66 to 2.10, p=0.57). The secondary outcomes were comparable between the groups at most assessment points. Manual lymph drainage may not have a preventive effect on the development of breast cancer-related lymphoedema in the short and long term. Netherlands Trial Register NTR 1055. [Devoogdt N, Geraerts I, Van Kampen M, De Vrieze T, Vos L, Neven P, Vergote I, Christiaens M-R, Thomis S, De Groef A (2018) Manual lymph drainage may not have a preventive effect on the development of breast cancer-related lymphoedema in the long term: a randomised trial. Journal of Physiotherapy 64: 245-254].

Short- and Long-term Effects of Case Management on Suicide Prevention among Individuals with Previous Suicide Attempts: a Survival Analysis.

BackgroundThis study examined the long-term preventive effects of a case management service on suicide reattempts, and clarified the factors related to suicide reattempts.MethodsWe reviewed the medical records of suicide attempters who visited the emergency department of Ulsan University Hospital from August 28, 2013 to July 31, 2017. A 4-week case management service was provided to consenting participants, either face-to-face or by telephone. Using survival analysis, we analyzed differences in the time to the next emergency department visit for a suicide attempt according to whether participants completed the case management service. We also assessed which characteristics of participants were associated with suicide reattempts.ResultsWe found no overall difference in time to suicide reattempt between case-managed participants and controls over the entire observation period (median period: 19 months). However, in the first 24 weeks after the initial suicide attempt, the case-managed group showed a longer time to reattempt than did the control group (log-rank test = 4.243; P = 0.039). A higher risk of reattempt was found among participants with the medical benefit type of health insurance compared to those with national health insurance (hazard ratio [HR], 5.134; P < 0.001) and among participants aged 20–39 compared to those aged ≥ 60 (HR, 3.502; P = 0.05).ConclusionCase management had only short-term benefits (within 24 weeks of initial suicide attempt). Risk factors for suicide reattempts were having a medical benefit health insurance and being aged 20–39 years.

Does intraperitoneal injection of propofol prior to detorsion improve testes weight and histopathological findings in a rat model?

ObjectivesTo determine the long-term preventive effects of intraperitoneal propofol on testicular ischemia–reperfusion injury in a rat model.Materials and methodsForty adult male albino Wistar rats were divided randomly into the following four groups according to the planned treatment (n=10 per group): group I, control; group II, sham-operated; group III, torsion/detorsion (T/D); and group IV, T/D plus propofol. Testicular ischemia was achieved by twisting the left testis 720° clockwise (ie, applying torsion) for 1 h. In the T/D plus propofol group (group IV), 50 mg/kg propofol was administered intraperitoneally 30 minutes before detorsion. Ipsilateral orchiectomy was performed under general anesthesia to determine the mean testicular weight and to enable histopathological examination of the testes using Johnsen’s mean testicular biopsy score 30 days after the surgical procedure in all groups.ResultsThe testicular weights in groups I, II, III, and IV were 1.65±0.32, 1.59±0.33, 1.11±0.56, and 1.08±0.50 g (mean ± SD), respectively. Testicular weight was significantly lower in the T/D groups (III and IV) than in both the control and sham-operated groups (I and II), but there was no improvement in testicular weight as a result of propofol administration. Similarly, Johnsen’s mean testicular biopsy score was lower in groups III and IV than in groups I and II, but no positive effect was conferred by the administration of propofol in group IV.ConclusionThe use of propofol in the treatment of testicular ischemia–reperfusion injury caused by testis torsion has no significant long-term therapeutic potential.

Long-term financing needs for HIV control in sub-Saharan Africa in 2015–2050: a modelling study

ObjectivesTo estimate the present value of current and future funding needed for HIV treatment and prevention in 9 sub-Saharan African (SSA) countries that account for 70% of HIV burden in...

Enduring effects of Preventive Cognitive Therapy in adults remitted from recurrent depression: A 10 year follow-up of a randomized controlled trial

BackgroundPrevention of recurrence is a challenge in the management of major depressive disorder (MDD). The long-term effects of Preventive Cognitive Therapy (PCT) in preventing recurrence in MDD are not known. MethodsA RCT comparing the addition of PCT to Treatment As Usual (TAU), versus TAU including patients with recurrent depression who were in remission at entry (N=172). PCT consisted of eight weekly group sessions. TAU involved standard treatment. Primary outcome is time to first recurrence of a depressive episode as assessed by blinded interviewers over 10 years based on DSM-IV-TR criteria. ResultsAlso over 10 years, the protective effect of PCT was dependent on the number of previous episodes a patient experienced. The protective effect intensified with the number of previous depressive episodes (Cox regression; p=.004, Hazard ratio=.576, 95% CI=.396–.837) and is mainly established within the first half of the 10 year follow-up period. For patients with more than three previous episodes (52% of the sample), PCT significantly increased the median survival time (713.0 days) versus patients that received TAU (205.0 days). No enduring effects were found on secondary outcomes. LimitationsDropout rates were relatively high for secondary outcomes, but relatively low for the primary outcome. Results were comparable after multiple imputation. ConclusionsPCT in remitted patients with multiple prior episodes has long-term preventive effects on time to recurrence. To reduce recurrence rates, booster sessions might be necessary. A personalized medicine approach might be necessary to reduce recurrence rates even further.

Long-term survival in pre-specified groups at risk in the Oslo Study, 1972-1973.

Using the Oslo Study of 1972-1973, we wished to compare the long-term mortality pattern up to 40 years, in both the healthy cardiovascular groups at supposedly high and low risk, and in some groups having cardiovascular disease at screening. At the screening, 16,203 (63% of those invited) men aged 40-49 years participated. Study groups were identified by means of questionnaires regarding diseases, blood pressure and measurements of total cholesterol, triglycerides and glucose. We identified six groups: very high cholesterol, very high blood pressure, very high glucose, non-smoking with non-elevated such risk factors, from a randomized diet and antismoking trial, and a randomized drug treatment in mild-to-moderate hypertension. Statistical analyses were by Cox regression analysis, with Kaplan-Meier graphs. The supposedly low-risk group had a total mortality of one-third of other groups, such as: men with hypertension, diabetes or hypercholesterolemia, or those whom participated in the two trials. Between these latter groups, we found 2-5 years of difference in their median survival time, but their absolute risk stayed at rather high levels through all the years, with the median remaining a lifetime that was 3-8 years shorter than the men whom were free of known cardiovascular disease, diabetes or hypertension. The long-term preventive effects on total mortality seem large, if the levels of the classical risk factors of blood pressure, total cholesterol and glucose can be adequately controlled, concurrently with a non-smoking behavior. The study indicated that non-smoking and a low total cholesterol value were the most important contributors to extended survival.

Long-term preventive effects of xylitol

Long-term preventive effects of xylitol

Preventive and therapeutic effect of treadmill running on chronic stress-induced memory deficit in rats

Previous results indicated that stress impairs learning and memory. In this research, the effects of preventive, therapeutic and regular continually running activity on chronic stress-induced memory deficit in rats were investigated. 70 male rats were randomly divided into seven groups as follows: Control, Sham, Stress-Rest, Rest-Stress, Stress-Exercise, Exercise-Stress and Exercise-Stress & Exercise groups. Chronic restraint stress was applied 6h/day for 21days and treadmill running 1h/day. Memory function was evaluated by the passive avoidance test. The results revealed that running activities had therapeutic effect on mid and long-term memory deficit and preventive effects on short and mid-term memory deficit in stressed rats. Regular continually running activity improved mid and long-term memory compared to Exercise-Stress group. The beneficial effects of exercise were time-dependent in stress conditions. Finally, data corresponded to the possibility that treadmill running had a more important role on treatment rather than on prevention on memory impairment induced by stress.

臨床 IaおよびIb群薬抵抗性心房細動に対するpilsicainide, flecainide ならびにbepridilの長期予防効果

臨床 IaおよびIb群薬抵抗性心房細動に対するpilsicainide, flecainide ならびにbepridilの長期予防効果