Preventive Therapy Research Articles

Meta-Analysis and Trial Sequential Analysis on Incisional Negative-Pressure Wound Therapy for Surgical Site Infection Prevention.

Meta-Analysis and Trial Sequential Analysis on Incisional Negative-Pressure Wound Therapy for Surgical Site Infection Prevention.

Applications of nanotechnology-mediated herbal nanosystems for ophthalmic drug.

In recent years, herbal nanomedicines have gained tremendous popularity for novel drug discovery. Nanotechnology has provided several advances in the healthcare sector, emerging several novel nanocarriers that potentiate the bioavailability and therapeutic efficacy of the herbal drug. The recent advances in nanotechnology with accelerated strategies of ophthalmic nanosystems have paved a new path for overcoming the limitations associated with ocular drug delivery systems, such as low bioavailability, poor absorption, stability, and precorneal drug loss. Ophthalmic drug delivery is challenging due to anatomical and physiological barriers. Due to the presence of these barriers, the herbal drug entry into the eyes can be affected when administered by following multiple routes, i.e., topical, injectables, or systemic. However, the advancement of nanotechnology with intelligent systems enables the herbal active constituent to successfully entrap within the system, which is usually difficult to reach employing conventional herbal formulations. Herbal-loaded nanocarrier drug delivery systems demonstrated enhanced herbal drug permeation and prolonged herbal drug delivery. In this current manuscript, an extensive search is conducted for original research papers using databases Viz., PubMed, Google Scholar, Science Direct, Web of Science, etc. Further painstaking efforts are made to compile and update the novel herbal nanocarriers such as liposomes, polymeric nanoparticles, solid lipid nanoparticles, nanostructure lipid carriers, micelles, niosomes, nanoemulsions, dendrimers, etc., which are mostly used for ophthalmic drug delivery system. This article presents a comprehensive survey of diverse applications used for the preventative measures and treatment therapy of varied eye disorders. Further, this article highlights the recent findings that the innovators are exclusively working on ophthalmic nanosystems for herbal drug delivery systems. The nanocarriers are promising drug delivery systems that enable an effective and supreme therapeutic potential circumventing the limitations associated with conventional ocular drug delivery systems. The nanotechnology-based approach is useful to encapsulate the herbal bioactive and prevent them from degradation and therefore providing them for controlled and sustained release with enhanced herbal drug permeation. Extensive research is still being carried out in the field of herbal nanotechnology to design an ophthalmic nanosystem with improved.

Lack of Prognostic Value of T-Wave Alternans for Implantable Cardioverter-Defibrillator Benefit in Primary Prevention.

New methods to identify patients who benefit from a primary prophylactic implantable cardioverter-defibrillator (ICD) are needed. T-wave alternans (TWA) has been shown to associate with arrhythmogenesis of the heart and sudden cardiac death. We hypothesized that TWA might be associated with benefit from ICD implantation in primary prevention. In the EU-CERT-ICD (European Comparative Effectiveness Research to Assess the Use of Primary Prophylactic Implantable Cardioverter-Defibrillators) study, we prospectively enrolled 2327 candidates for primary prophylactic ICD. A 24-hour Holter monitor reading was taken from all recruited patients at enrollment. TWA was assessed from Holter monitoring using the modified moving average method. Study outcomes were all-cause death, appropriate shock, and survival benefit. TWA was assessed both as a contiguous variable and as a dichotomized variable with cutoff points <47 μV and <60 μV. The final cohort included 1734 valid T-wave alternans samples, 1211 patients with ICD, and 523 control patients with conservative treatment, with a mean follow-up time of 2.3 years. TWA ≥60 μV was a predicter for a higher all-cause death in patients with an ICD on the basis of a univariate Cox regression model (hazard ratio, 1.484 [95% CI, 1.024-2.151]; P=0.0374; concordance statistic, 0.51). In multivariable models, TWA was not prognostic of death or appropriate shocks in patients with an ICD. In addition, TWA was not prognostic of death in control patients. In a propensity score-adjusted Cox regression model, TWA was not a predictor of ICD benefit. T-wave alternans is poorly prognostic in patients with a primary prophylactic ICD. Although it may be prognostic of life-threatening arrhythmias and sudden cardiac death in several patient populations, it does not seem to be useful in assessing benefit from ICD therapy in primary prevention among patients with an ejection fraction of ≤35%.

Summary for Patients: Benefits and Risks Associated With Statin Therapy for Primary Prevention in Old and Very Old Adults.

Summary for Patients: Benefits and Risks Associated With Statin Therapy for Primary Prevention in Old and Very Old Adults.

Benefits and Risks Associated With Statin Therapy for Primary Prevention in Old and Very Old Adults : Real-World Evidence From a Target Trial Emulation Study.

There is little consensus on using statins for primary prevention of cardiovascular diseases (CVDs) and all-cause mortality in adults aged 75 years or older due to the underrepresentation of this population in randomized controlled trials. To investigate the benefits and risks of using statins for primary prevention in old (aged 75 to 84 years) and very old (aged ≥85 years) adults. Sequential target trial emulation comparing matched cohorts initiating versus not initiating statin therapy. Territory-wide public electronic medical records in Hong Kong. Persons aged 75 years or older who met indications for statin initiation from January 2008 to December 2015 were included. Participants with preexisting diagnosed CVDs at baseline, such as coronary heart disease (CHD), were excluded from the analysis. Among 69 981 eligible persons aged 75 to 84 years and 14 555 persons aged 85 years or older, 41 884 and 9457 had history of CHD equivalents (for example, diabetes) in the respective age groups. Initiation of statin therapy. Incidence of major CVDs (stroke, myocardial infarction, or heart failure), all-cause mortality, and major adverse events (myopathies and liver dysfunction). Of 42 680 matched person-trials aged 75 to 84 years and 5390 matched person-trials aged 85 years or older (average follow-up, 5.3 years), 9676 and 1600 of them developed CVDs in each age group, respectively. Risk reduction for overall CVD incidence was found for initiating statin therapy in adults aged 75 to 84 years (5-year standardized risk reduction, 1.20% [95% CI, 0.57% to 1.82%] in the intention-to-treat [ITT] analysis; 5.00% [CI, 1.11% to 8.89%] in the per protocol [PP] analysis) and in those aged 85 years or older (ITT: 4.44% [CI, 1.40% to 7.48%]; PP: 12.50% [CI, 4.33% to 20.66%]). No significantly increased risks for myopathies and liver dysfunction were found in both age groups. Unmeasured confounders, such as lifestyle factors of diet and physical activity, may exist. Reduction for CVDs after statin therapy were seen in patients aged 75 years or older without increasing risks for severe adverse effects. Of note, the benefits and safety of statin therapy were consistently found in adults aged 85 years or older. Health Bureau, the Government of Hong Kong Special Administrative Region, China, and National Natural Science Foundation of China.

Rationale, models, and impact of workplace-based psychotherapeutic services

Mental illnesses and behavioral disorders are very common among the working population, affecting up to athird of employees each year, and are associated with great suffering, the risk of chronicity, and the loss of employment. Economically, mental illnesses cause high costs. In order to mitigate these consequences and increase the chances of recovery, rapid diagnosis, early and appropriate treatment where necessary, and-over and above the usual psychotherapy approach-attention to the work-related causes are of crucial importance.Psychotherapeutic Consultation at the Workplace (PT-A) attempts to meet these requirements. It offers psychotherapeutic help at short notice and close to the workplace for employees suffering from mental stress; provides (depending on the problem) counseling, diagnostics, prevention, and short-term or bridging therapy; and supports reintegration after alonger period of mental illness. It is helpful to cooperate closely with the company medical service, which consults the PT‑A, refers employees to it, provides information on the company situation, and can support reintegration if necessary. Funding is often provided by the company but can also be provided by health insurance companies in integrated care models.This article begins by describing the history and principles of PT‑A and the role of work stress in the development of psychological and psychosomatic disorders. The implementation of PT‑A is then outlined using two examples. Finally, the current study "Early Intervention at the Workplace" ("Frühe Intervention am Arbeitsplatz" [friaa]), to which several articles in this special issue refer, is briefly presented.

Effects of voluntary and forced physical exercise on the retinal health of aging Wistar rats.

Aging is accompanied by an increased prevalence of degenerative conditions, including those affecting ocular health, which significantly impact quality of life and increase the burden on healthcare systems. Among these, retinal aging is of particular concern due to its direct link to vision impairment, a leading cause of disability in the elderly. Vision loss in the aging population is associated with heightened risks of cognitive decline, social isolation, and morbidity. This study addresses the critical gap in our understanding of modifiable lifestyle factors, such as physical exercise, that may mitigate retinal aging and its related pathologies. We investigated the effects of different exercise regimens-voluntary (recreational-type) and forced (high-intensity)-on the retinal health of aging Wistar rats (18-month-old), serving as a model for studying the translational potential of exercise interventions in humans. Male Wistar rats were divided into four groups: a young control (3-month-old) for baseline comparison, an aged sedentary control, an aged group engaging in voluntary exercise via a running wheel in their cage, and an aged group subjected to forced exercise on a treadmill for six sessions of 20 min each per week. After a 6-month experimental period, we assessed retinal function via electroretinography (ERG), measured retinal thickness histologically, and analyzed protein expression changes relevant to oxidative stress, inflammation, and anti-aging mechanisms. Our findings reveal that voluntary exercise positively impacts retinal function and morphology, reducing oxidative stress and inflammation markers while enhancing anti-aging protein expression. In contrast, forced exercise showed diminished benefits. These insights underscore the importance of exercise intensity and preference in preserving retinal health during aging. The study highlights the potential of recreational physical activity as a non-invasive strategy to counteract retinal aging, advocating for further research into exercise regimens as preventative therapies for age-related ocular degenerations.

Cardiac magnetic resonance to predict appropriate therapies in secondary prevention

Abstract Introduction Implantable cardioverter-defibrillator (ICD) therapy plays a pivotal role in the management of patient’s survivors of life-threatening ventricular arrhythmias (secondary prevention). Risk of recurrence may be related to presence of myocardial scar and its components (including core mass, border zone (BZ) mass, and BZ channels) assessed with late gadolinium enhancement cardiac magnetic resonance (LGE-CMR). Purpose Our study aims to analyze the role of imaging in predicting the risk of recurrent ventricular arrhythmias and improving the risk stratification for appropriate ICD therapy in patients receiving an ICD for secondary prevention. Methods From 2015 to 2020, a total of 111 patients with LGE-CMR before ICD implantation for secondary prevention. Scar tissue including core, BZ and BZ channels were automatically detected by specialized investigational software in patients with LGE-CMR. Patients were followed until a new event was detected. Results The mean age was 65.4 ± 11.4 years; 87% were men; 55% had ischemic cardiomyopathy. The mean left ventricular ejection fraction was 37.8 % ± 14.31%. Patients were followed for a median of 3.26 years (IQR 1.4-4.9). Within the first year of follow-up 22% of patients had received an appropriate therapy, 39% within 3 years and 53% within 6 years. Chronic kidney disease and New York Heart Association (NYHA) class were associated with the primary endpoint [HR 1.94(1.06-3.55), P-value 0.032)] and [HR 1.86 (1.19-2.91), P-value 0.006)], respectively. Regarding CMR characteristics, BZ percentage was also associated with appropriate ICD therapy in the follow up [HR 1.04(1-1.08), P-value 0.048)]. Other CMR parameter, such as BZ mass, BZ core %, BZ core mass and core mass showed a trend to predict ICD therapies during follow-up. ROC curve analysis with Youden’s index defined an optimal BZ percentage cutoff value for recurrence prediction of 9.5% [HR 0.49 (0.28-0.85)]. Conclusion In patients receiving an ICD for secondary prevention, chronic kidney disease, NYHA class and BZ percentage analyzed by LGE-CMR were predictors of recurrent ventricular arrhythmia. A cutoff of BZ of 9.5% could be used to select patients with high risk of recurrence.

One-year effectiveness and safety outcomes of edoxaban treatment in Chinese patients with atrial fibrillation: First snapshot of more than 4,800 patients from the ETNA-AF-China study

Abstract Background Direct oral anticoagulants (DOACs) have become the first-line therapy for ischaemic stroke prevention in atrial fibrillation (AF) patients. Data on the effectiveness and safety of single DOAC in large Chinese populations are scarce. Purpose We firstly present the one-year outcome data of edoxaban treatment in 5001 Chinese AF patients. Methods This is a multi-centre, prospective, observational study, ETNA-AF-China, conducted in 89 centres from four economic regions in Mainland of China with a follow-up of two years. Primary endpoint of safety [bleeding events including intracranial hemorrhage (ICH), all-cause and cardiovascular (CV) mortality] and efficacy endpoints [stroke, systemic embolic events (SEE), transient ischemic attack (TIA)] were adjudicated. Annualised event rates and Kaplan­Meier (KM) survival curves are given. Results A total of 4822 patients (57.1% male) using edoxaban (60 mg OD: n=2614, 30 mg OD: n=2208) who completed one-year follow-up were included in the full analysis set. The mean (SD) age of the overall patient population was 70.3 (9.5) years, CHA2DS2-VASc and HAS-BLED scores were 2.9 (1.4), 1.7 (1.0), with creatinine clearance (CrCl) of 71.2 (27.7) mL/min. Patients receiving 30 mg OD edoxaban at baseline were older (73.4 vs 67.7 years), with higher CHA2DS2-VASc score (3.3 vs 2.6), larger percentage of frail (9.9% vs 3.4%), and higher renal impairment (defined as CrCl ≤80 mL/min, 70.3% vs 42.9%). Annualised rates for all-cause and cardiovascular death in the overall population were very low with 2.22%/year and 0.41%/year, respectively. (Figure 1) The death rates were nearly three times lower in those receiving standard dose (60 mg) than reduction dose (30 mg) of edoxaban. Annualised event rates for all stroke/SEE (1.03%/year) and ischemic stroke (0.60%/year) were similar between two dose groups. Overall, annualised rates for major bleeding (1.03%/year), ICH (0.18%/year), major gastrointestinal (GI) bleeding (0.48%/year) events were relatively low, and those on 60 mg dose experienced less above bleeding events. Cumulative survival analysis demonstrated a slow increase in time-to-first event curve of all-cause death; and from baseline to 1-year follow-up, significant lower events of all-cause death (log-rank p&amp;lt;0.001), major bleeding (p=0.002) in 60 mg vs 30 mg edoxaban groups. (Figure 2). Conclusion Low incidences of major bleeding, notably ICH, major GI bleeding, and CV death were observed in unselected 4822 patients with AF during 1-year of edoxaban treatment. These findings confirm the effectiveness and safety of routine edoxaban use in China, consistent with other countries, and reinforce the results of the ENGAGE AF-TIMI 48 trial.Figure 1Figure 2

P.004 Real-world effectiveness of intravenous eptinezumab in patients with chronic migraine and previous subcutaneous preventive migraine treatment

Background: Since 2018, several CGRP-targeted therapies have entered the migraine market, including eptinezumab. Minimal evidence exists evaluating the real-world effectiveness of switching from a subcutaneous to an intravenous anti-CGRP mAb. Methods: An observational, multi-site (n=4), US-based study, REVIEW evaluated real-world experiences of patients with chronic migraine (CM) treated with eptinezumab using a chart review, patient survey, and physician interviews. Adults (≥18 years) with a diagnosis of CM who had completed ≥2 consecutive eptinezumab infusion cycles were eligible. Results: Enrolled patients were primarily female (83%, 78/94), had a mean age of 49 years and a mean migraine diagnosis duration of 15.4 years. All patients (94/94) self-reported prior preventive therapy with 89% (84/94) reporting prior subcutaneous anti-CGRP mAb use (i.e., fremanezumab, galcanezumab, or erenumab). Regardless of prior exposure to a CGRP ligand or receptor blocker, the number of “good” days/month more than doubled following eptinezumab. Patients experienced a similar mean change in the number of “good” days/month regardless of the number and type of previous subcutaneous anti-CGRP mAb used. Conclusions: This real-world, patient survey showed that patients with prior exposure to subcutaneous anti-CGRP mAbs had high overall satisfaction with the effectiveness of eptinezumab treatment regardless of the number and type of previous therapies used.

#1572 Recurrent parvovirus B19 infection-associated pure red cell aplasia in kidney transplantation

Abstract Background and Aims Anemia is frequent in kidney transplant (KT) recipients, with multiple potential causes. Parvovirus B19 (PVB19) infection-associated pure red cell aplasia (PRCA) becomes an important diagnosis in KT recipients experiencing persistent anemia, in whom other etiologies have been excluded. PVB19-associated PRCA is described in up to 27% of KT recipients with anemia and recurrent disease in up to 33% of cases. The authors describe a case of a recurrent PVB19-associated PRCA in a KT recipient. Method - Results A 42-year-old male with chronic kidney disease of unknown etiology underwent KT from a deceased donor after circulatory death in January 2021. He received induction immunosuppression (IS) with thymoglobulin and maintenance IS with prednisolone, tacrolimus, and mycophenolate mofetil (MMF). Three months after KT, the patient complained of progressive asthenia, and normocytic normochromic (NN) anemia was detected. A thorough investigation revealed normal leucocyte and platelet counts, low reticulocyte count, and no signs of bacterial infection, iron deficiency, or hemolysis; thyroid function, erythropoietin, folate, and vitamin B12 levels were normal, direct Coombs test was negative and no monoclonal spike was detected on protein electrophoresis. Endoscopic studies and cervico-thoraco-abdomino-pelvic computer tomography were unremarkable. Serum PCR of PVB19 was positive and confirmed the diagnosis of PVB19-associated PRCA. MMF was discontinued but anemia continued aggravating (nadir hemoglobin [Hg] level of 6.6 g/dL) with a sustained PVB19 load. He was admitted to the hospital, received blood transfusions, and was started on intravenous immunoglobulin (IVIG) 2 g/kg. A bone marrow aspirate was performed and was compatible with recovery after erythroid aplasia. The patient was discharged with Hg 8 g/dL and reduced PVB19 load. Although MMF remained suspended, and close monitoring of Hg and PVB19 load was performed, four months later he developed recurrent PVB19-associated PRCA, which motivated another hospital admission for IVIG with excellent response. In addition, he presented kidney dysfunction, and a kidney biopsy revealed borderline acute T-cell mediated rejection. In this setting, IS was altered to TRANSFORM SCHEEME. Four months later, he presented a second recurrence of PVB19-associated PRCA, requiring new hospitalization and treatment with IVIG. Considering the recurrent PVB19-associated PRCA, in a patient with chronic allograft dysfunction, high immunologic risk, and the foscarnet's probable nephrotoxicity, preventive therapy with IVIG (0.4 mg/kg) every 4 weeks was started. After 7 months of preventive IVIG infusion, no relapse was identified, the Hg is 11.5 g/dL (and increasing, without erythropoiesis stimulants) and the PVB19 load remains low. Conclusion PVB19-associated PRCA is characterized by persistent NN anemia with low reticulocyte counts, which is unresponsive to erythropoietin. One significant risk factor is induction IS, particularly thymoglobulin. In the setting of solid organ transplants, the absence of PVB19 antibodies does not exclude this diagnosis and viral detection should be performed. The initial therapeutic approach involves reducing IS. However, the risk of allograft rejection must be acknowledged. If this approach proves insufficient, IVIG treatment is usually successful. In our patient, considering the facts that allograft rejection limits the reduction of IS, the need for blood transfusions, and the inherent immunization, in a young patient that will possibly require a second KT, the undesirable nephrotoxicity of foscarnet, the successful response to IVIG, and patient's quality of life, chronic IVIG therapy was thought to be the best choice and proved efficacious in preventing relapses. Despite the absence of precise guidelines for chronic PVB19 infection management, maintenance therapy with prolonged IVIG infusions may be a therapeutic option for recurrent PRCA, but more studies are necessary to define the appropriate duration of treatment.

#2458 Factors associated with cytomegalovirus infection in kidney transplant patients: analysis from a nationwide registry data

Abstract Background and Aims Cytomegalovirus (CMV) has had a significant impact on solid organ transplantation. It can affect allograft function and increase patient morbidity and mortality. We have made several efforts to prevent CMV infection after kidney transplantation (KT), but we have not yet been able to prevent it satisfactorily. Drugs were used as preventive therapy or preemptive therapy, but they did not completely prevent the diseases. Therefore, it will be possible to reduce CMV infection by taking actions against factors that can easily cause CMV infection. We investigated factors that make CMV infection more likely and explored the effects of CMV infection using The Korean Organ Transplantation Registry (KOTRY) datasets. Method We used the data from the KOTRY datasets. A total of 7545 KT recipients were analysed. Results The mean age of the subjects was 49.7 ± 11.5 years (range, 19-80). Among the 7545 subjects, 58.6% were male. Three hundred and twenty-four (4.2%) subjects had CMV infection (CMV group). There were 4827 (64%) living donors, 2717 (36%) cadaveric donors, and 1338 (17.3%) ABO incompatible donors. Of the total, 95% were transplanted from positive to positive CMV IgG, and 1.9% were from positive to negative. Although preventive treatment is performed in the second cases, in most cases preemptive therapy is performed. The age was 49.6 ± 11.5 in the no CMV group and 51.4 ± 12.6 in the CMV group (P = 0.013). There was no difference in sex, weight and BMI in both cases. The causes of end stage renal disease were glomerulonephritis, DM, and hypertension in that order, and there was no difference in the rates of diabetes and hypertension between the two groups. There was no difference in the desensitization rate at 24% in the no CMV group and 23% in the CMV group. At the time of discharge after surgery, the tacrolimus dose was 6.4 mg/d±3.6 in the no CMV group and 6.3 ± 3.8 mg/d in the CMV group (P = 0.89). Tacrolimus concentration (C0) was 8.0 ± 2.6 ng/ml in the no CMV group and 8.9 ± 2.4 ng/ml in the CMV group. It was higher in the CMV group (P = 0.002). When divided into 3 tertiles based on C0, the break points were 6.7 and 8.9 ng/ml. There was a higher incidence of CMV in the third tertile group compared to the first and second tertiles, but there was no difference between the first and second groups. When the metabolic rate (tacrolimus concentration divided by dose) was divided into three groups, CMV occurred more frequently in the group with the lower metabolic rate, at 3.9% in the group with the lowest tertile and 2.3% in the highest tertile (P = 0.046). At 6 months, tacrolimus dose was 4.3 ± 2.4 mg/d in the no CMV group and 3.9 ± 2.3 mg/d in the CMV group, which was lower in the CMV group (P = 0.005). Tacrolimus concentration was 6.8 ± 2.4 ng/ml in the no CMV group and 6.4 ± 2.3 ng/ml in the CMV group, which was lower in the CMV group (P = 0.004). There was no difference according to metabolic rate. At discharge (62.5 ± 25.7 vs. 54.5 ± 26.5), at 6 month (56.0 ± 22.3 vs. 47.9 ± 19.0), and at 1 year (57.2 ± 20.0 vs. 48.8 ± 19.6 mL/min/1.73 m2), eGFR in the No CMV group was higher than that in the CMV group (P &amp;lt; 0.005). One thousand two hundred and sixty-four (16.8%) patients showed acute rejection within 1 year. Acute rejection occurred within 1 year in 36.4% of the CMV group and 15.9% of the no CMV group (P &amp;lt; 0.001). Delayed graft function occurred in 4.6% of the CMV group and 5.5% of the no CMV group (P &amp;lt; 0.001). Conclusion CMV was more common in older people, those with higher tacrolimus concentrations, and those with lower tacrolimus metabolic rates. The risk increases when the concentration exceeds 8.9 ng/ml, and after reducing the dose, the dose and concentration were lower in the CMV group at 6 month and 1 year. Although the dose was later reduced in the CMV group, more acute rejections occurred within 1 year, which suggests that CMV infection can trigger rejections. Delayed graft function occurred less frequently in the CMV group, which may be related to the higher concentration of tacrolimus.

Can Daily Dietary Choices Have a Cardioprotective Effect? Food Compounds in the Prevention and Treatment of Cardiometabolic Diseases

Cardiovascular diseases accompanying metabolic syndrome comprise one of the leading causes of death worldwide. The medical community undertakes attempts to improve treatment options and minimize cardiovascular diseases’ numerous consequences and exacerbations. In parallel with pharmacotherapies provided by physicians, nutritionists are developing strategies for diet therapy and prevention based on lifestyle changes, with high success rates. Consumption of specified food compounds included in various products with proven protective properties can be helpful in this regard. Due to the wide possibilities of diet in metabolic health promotion, it seems necessary to systematize information about the metabolically protective and cardioprotective properties of fiber, probiotic bacteria, plant sterols, folic acid, vitamins B12, C, and E, PUFAs, lycopene, polyphenols, arginine, CoQ10, and allicin. The aim of this review was to present the food compounds with potential use in cardiometabolic prevention and diet therapy based on the latest available literature.

Life satisfaction and awareness of meaningful activities among middle-aged adults: A population-based study

Introduction: Meaningful activities have been suggested to contribute to life satisfaction. Investigating the association between the awareness of meaningful activities and life satisfaction will help us develop a population-based occupational therapy strategy. The purpose of this study was to investigate the proportion of people who were aware of meaningful activities among middle-aged adults, and the relationship between the awareness of meaningful activities and life satisfaction. Method: A cross-sectional analysis was conducted on 2698 middle-aged adults who participated in an online survey conducted in Japan by the Y-Cloud system. Participants responded to demographic questions, life satisfaction, and awareness of meaningful activities. We examined the association between the awareness of meaningful activities and life satisfaction using binomial logistic regression analysis. Results: Of the respondents, 77.4% were aware of meaningful activities. Binomial logistic regression analysis adjusted for covariates showed that the awareness of meaningful activities was significantly associated with higher life satisfaction (odds ratio, 2.97; 95% confidence interval: 2.45–3.61, p &lt; 0.001). Conclusion: The results suggest the value of presenting that the awareness of meaningful activities should be considered in preventive population-based occupational therapy strategies for life satisfaction.

Position statement of the Brazilian society of Rheumatology on mesna use as a preventive therapy for bladder disease in patients with systemic autoimmune diseases and systemic vasculitis under cyclophosphamide treatment

ObjectiveTo review current literature to support the use of mesna as a preventive therapy for hemorrhagic cystitis and bladder cancer in patients with systemic autoimmune diseases and systemic vasculitis treated with cyclophosphamide.Materials and methodsThe search for articles was conducted systematically through MEDLINE, LILACS, Cochrane Library, and Embase databases. Only articles in English were selected. For available records, titles and abstracts were selected independently by two investigators.ResultsEighteen studies were selected for analysis. The known adverse effects of cyclophosphamide were hematological toxicity, infections, gonadal toxicity, teratogenicity, increased risk for malignancy and hemorrhagic cystitis. Long-term toxicity was highly dependent on cyclophosphamide cumulative dose. The risk of bladder cancer is especially higher in long-term exposure and with cumulative doses above 36 g. The risk remains high for years after drug discontinuation. Hemorrhagic cystitis is highly correlated with cumulative dose and its incidence ranges between 12 and 41%, but it seems to be lower with new regimens with reduced cyclophosphamide dose. No randomized controlled trials were found to analyze the use of mesna in systemic autoimmune rheumatic diseases and systemic vasculitis. Retrospective studies yielded conflicting results. Uncontrolled prospective studies with positive results were considered at high risk of bias. No evidence was found to support the use of mesna during the treatment with cyclophosphamide for autoimmune diseases or systemic vasculitis to prevent hemorrhagic cystitis and bladder cancer. In the scenarios of high cumulative cyclophosphamide dose (i.e., > 30 g), patients with restricted fluid intake, neurogenic bladder, therapy with oral anticoagulants, and chronic kidney disease, mesna could be considered.ConclusionThe current evidence was found to be insufficient to support the routine use of mesna for the prophylaxis of hemorrhagic cystitis and bladder cancer in patients being treated for systemic autoimmune diseases and systemic vasculitis with cyclophosphamide. The use may be considered for selected cases.

Spatial distribution and determinants of intermittent preventive treatment for malaria during pregnancy: a secondary data analysis of the 2019 Ghana malaria indicators survey

BackgroundMalaria during pregnancy is associated with poor maternal, foetal, and neonatal outcomes. To prevent malaria infection during pregnancy, the World Health Organization recommended the use of intermittent preventive therapy with sulfadoxine-pyrimethamine (IPTp-SP) in addition to vector control strategies. Although Ghana’s target is to ensure that all pregnant women receive at least three (optimal) doses of SP, the uptake of SP has remained low; between 2020 and 2022, only 60% of pregnant women received optimal SP during their most recent pregnancy. This study sought to map the geospatial distribution and identify factors associated with SP uptake during pregnancy in Ghana.MethodsSecondary data analysis was conducted using the 2019 Ghana Malaria Indicator Survey dataset. The data analysed were restricted to women aged 15–49 years who reported having a live birth within the two years preceding the survey. A modified Poisson regression model was used to determine factors associated with SP uptake during pregnancy. Geospatial analysis was employed to map the spatial distribution of optimal SP uptake across the ten regions of Ghana using R software.ResultsThe likelihood that pregnant women received optimal SP correlated with early initiation of first antenatal care (ANC), number of ANC contacts, woman’s age, region of residence, and family size. Overall, the greater the number of ANC contacts, the more likely for pregnant women to receive optimal SP. Women with four or more ANC contacts were 2 times (aPR: 2.16; 95% CI: [1.34–3.25]) more likely to receive optimal SP than pregnant women with fewer than four ANC contacts. In addition, early initiation and a high number of ANC contacts were associated with a high number of times a pregnant woman received SP. Regarding spatial distribution, a high uptake of optimal SP was significantly observed in the Upper East and Upper West Regions, whereas the lowest was observed in the Eastern Region of Ghana.ConclusionsIn Ghana, there were regional disparities in the uptake of SP during pregnancy, with the uptake mainly correlated with the provision of ANC services. To achieve the country’s target for malaria control during pregnancy, there is a need to strengthen intermittent preventive treatment for malaria during pregnancy by prioritizing comprehensive ANC services.

Patient knowledge about risk factors, achievement of target values and guideline adherent secondary prevention therapies 12 months after acute myocardial infarction.

The prospective GULLIVE-R study aimed to evaluate adherence to guideline recommended secondary prevention, physicians' and patients' estimation of cardiac risk, and patients' knowledge about target values of risk factors after acute myocardial infarction (AMI). We performed a prospective study enrolling patients 9-12 months after AMI. Guideline recommended secondary prevention therapies and physicians as well as patients' estimation about their risk, and patients' knowledge about target values were prospectively collected. Between 07/2019 and 06/2021 a total of 2509 outpatients were enrolled in 150 German centers 10 months after AMI. The mean age was 66 years, 26.4% were women, 45.3% had STEMI, 54.7% had NSTEMI, 93.6% had revascularization (84.0% PCI, 7.4% CABG, 1.8% both). Guideline recommended secondary drug therapies were prescribed in over 80% of patients, while only about 50% received all five recommended drugs (aspirin, P2Y12 inhibitors, statins, beta-blockers, RAAS inhibitors) and regular exercise was performed by only one third. About 90% of patients felt well informed about secondary prevention, but the correct target value for blood pressure was known in only 37.9% and for LDL-C in only 8.2%. Both, physicians and patients underestimated the objective risk for future AMIs as determined by the TIMI risk score for secondary prevention. There is still room for improvement in patient education and implementation of guideline recommended non-pharmacological and pharmacological secondary prevention therapies in patients in the chronic phase after AMI.

Comparing patterns of recent and remote Mycobacterium tuberculosis infection determined using the QuantiFERON-TB Gold Plus assay in a high TB burden setting.

One quarter of the world's population is estimated to be infected with Mycobacterium tuberculosis. Identifying recent TB infection (TBI) offers an avenue to targeted TB preventative therapy provision, and prevention to disease progression. However, detecting recent TBI remains challenging. The QuantiFERON-TB Gold Plus assay (QFT-Plus) claims to have improved sensitivity in detecting recent TBI, by the addition of the TB2 antigen tube to the TB1 tube used in previous tests. TB2 detects CD8-mediated interferon gamma response, a potential marker of recent infection. We compared QFT-Plus TB1 and TB2 responses in individuals with recent and remote infection in high-burden settings. The Tuberculosis Reduction through Expanded Antiretroviral Treatment and TB Screening (TREATS) Project followed a cohort of adolescents and young people (AYP) aged 15-24 years in Zambia and South Africa to determine TBI incidence measured by QFT-Plus over 24 months. We categorised individuals with QTF-Plus positive result into recent and remote infection. We compared their TB1 and TB2 responses and the antigen tube differential [TB2-TB1], an indicator of CD8-activity, using logistic regression. At baseline, 3876 AYP, 1852/3876 (47.8%) were QFT-Plus positive whilst 2024/3876 (52.2%) QFT-Plus negative. Of the QFT-Plus baseline positives, 1069/1852 (57.7%) tested positive at both 12 and 24 months-remote infection. Of the QFT-Plus baseline negatives, 274/2024(13.3%) converted within a 12-month period- recent infection. TB1 and TB2 responses were higher in remote than recent infection. In recent infection, TB2 responses were greater than TB1 responses. The mean differential was 0.01 IU/ml in recent and -0.22 IU/ml in remote infection, (p = 0.145). The quantitative QFT-Plus results did not appear to reflect a marked distinction between recent and remote infection. Further analysis of the responses of infected individuals who developed disease is required to determine whether any signal in QFT-Plus results may predict progression to disease.

Incident heart failure in chronic kidney disease: proteomics informs biology and risk stratification.

Incident heart failure (HF) among individuals with chronic kidney disease (CKD) incurs hospitalizations that burden patients and health care systems. There are few preventative therapies, and the Pooled Cohort equations to Prevent Heart Failure (PCP-HF) perform poorly in the setting of CKD. New drug targets and better risk stratification are urgently needed. In this analysis of incident HF, SomaScan V4.0 (4638 proteins) was analysed in 2906 participants of the Chronic Renal Insufficiency Cohort (CRIC) with validation in the Atherosclerosis Risk in Communities (ARIC) study. The primary outcome was 14-year incident HF (390 events); secondary outcomes included 4-year HF (183 events), HF with reduced ejection fraction (137 events), and HF with preserved ejection fraction (165 events). Mendelian randomization and Gene Ontology were applied to examine causality and pathways. The performance of novel multi-protein risk models was compared to the PCP-HF risk score. Over 200 proteins were associated with incident HF after adjustment for estimated glomerular filtration rate at P < 1 × 10-5. After adjustment for covariates including N-terminal pro-B-type natriuretic peptide, 17 proteins remained associated at P < 1 × 10-5. Mendelian randomization associations were found for six proteins, of which four are druggable targets: FCG2B, IGFBP3, CAH6, and ASGR1. For the primary outcome, the C-statistic (95% confidence interval [CI]) for the 48-protein model in CRIC was 0.790 (0.735, 0.844) vs. 0.703 (0.644, 0.762) for the PCP-HF model (P = .001). C-statistic (95% CI) for the protein model in ARIC was 0.747 (0.707, 0.787). Large-scale proteomics reveal novel circulating protein biomarkers and potential mediators of HF in CKD. Proteomic risk models improve upon the PCP-HF risk score in this population.

Development of EBV Related Diffuse Large B-cell Lymphoma in Deficiency of Adenosine Deaminase 2 with Uncontrolled EBV Infection

Deficiency of Adenosine Deaminase 2 (DADA2) patients presenting with primary immunodeficiency are at risk of uncontrolled EBV infection and secondary malignancies including EBV-related lymphoproliferative disorders (LPD). This paper describes the first case of EBV related diffuse large B-cell lymphoma in a patient with DADA2 and uncontrolled EBV infection. Consideration should be given to monitoring for EBV viraemia and to preventative EBV specific therapy in DADA2 and patients with at risk primary immunodeficiencies. A type I interferon (IFN) gene signature is associated with DADA2 though its association with immune dysregulation is unclear.