Preventive Therapy Research Articles

Endoscopic vacuum therapy (eVAC) combined with continuous perianastomotic irrigation for prevention of anastomotic leak after surgical ampullectomy.

Transduodenal surgical ampullectomy (tAMP) with papillary reimplantation is a valid alternative to pancreaticoduodenectomy for lesions of the periampullary region not amenable to endoscopic resection. As tAMP is burdened by high rates of biliopancreatic-enteric anastomotic leak, we tested preventive endoluminal vacuum therapy (eVAC) combined with post-operative continuous perianastomotic irrigation (CPI) to reduce such anastomotic leak. Between 10/2013 and 09/2023, 37 patients undergoing laparotomic tAMP (with or without jejunal transposition) and papillary reimplantation at Hirslanden Klinik Zurich were retrospectively analysed; of these, 16 received prophylactic eVAC combined with CPI, while the remaining represented the historical cohort. The eVAC-CPI-group and the historical-cohort were homogeneous in demographic characteristics. Surgery in the prophylactic eVAC-CPI-group lasted about 30min longer due to eVAC application (p = 0.008). The biliopancreatico-enteric anastomotic leak rates were 6.2% in the eVAC-CIP-group vs. 19.0% in the historical-cohort (p = 0.266). Along, a strong trend of less severe post-operative complications in general (p = 0.073), and borderline-significantly less cases of acute pancreatitis (p = 0.057) and tAMP-related re-operations or re-interventions (p = 0.057) in particular, were observed in the eVAC-CPI-group. The only anastomotic leak in the eVAC-CPI-group was successfully managed through repeated cycles of eVAC. The device was well tolerated by all patients; no vacuum/irrigation-related complications or malfunctioning occurred. Our study is the first to provide some technical insights demonstrating the safety and feasibility of a prophylactic approach with eVAC and perianastomotic irrigation to reduce anastomotic leak after tAMP. Increasing the number of subjects will confirm the benefit of our promising results.

High disease burden and healthcare resource usage in patients with acute porphyria-A population-based analysis.

Acute porphyria is a chronic recurrent disease with late diagnosis, heterogeneous clinical presentations and potentially devastating complications. The study aimed at providing real-world evidence on the natural course of acute porphyria, patient characteristics, disease burden, and healthcare utilization before diagnosis. This observational study used anonymized claims data covering 8 365 867 persons from German statutory health insurance, spanning 6 years (2015-2020). Patients with at least one diagnosis of acute porphyria during the index period (2019-2020) were classified into three groups by attack frequency. These findings were compared with two age- and sex-adjusted reference groups: the general population and fibromyalgia patients. Prevalence over the index period was calculated for all porphyria patients and those with active acute porphyria. We revealed a prevalence of 79.8 per 1 000 000 for acute porphyria, with 12.9 per 1 000 000 being active cases. Acute porphyria patients, particularly with frequent attacks, demonstrated a higher comorbidity burden compared to the general population. Within the year before the recorded diagnosis, patients with acute porphyria required a median of 23.0 physician visits, significantly higher than the general population's 16.0. Additionally, 33.8% were hospitalized at least once during this period, a notably higher proportion than the general population (19.3%). This study's findings, collected before the introduction of givosiran, as the first approved preventive therapy for acute porphyria in Europe, highlight the need for healthcare strategies and policies tailored to the complex needs of acute porphyria patients. The significant healthcare demands, heightened comorbidity burden, and increased healthcare system utilization emphasize the urgency of developing a comprehensive support infrastructure for these patients. Also, these acute porphyria real-world findings provide additional insights on disease characteristics in Germany.

Risk score prediction for bacteriologically confirmed tuberculosis among adults with HIV on antiretroviral therapy in northwest Ethiopia: prognostic model development.

This study was aimed at developing a risk score prediction model for bacteriologically confirmed tuberculosis (TB) among adults with HIV receiving antiretroviral therapy in Ethiopia. An institutional-based retrospective follow-up study was conducted among 569 adults with HIV on ART. We used demographic and clinical prognostic factors to develop a risk prediction model. Model performance was evaluated by discrimination and calibration using the area under the receiver operating characteristic (AUROC) curve and calibration plot. Bootstrapping was used for internal validation. A decision curve analysis was used to evaluate the clinical utility. Opportunistic infection, functional status, anemia, isoniazid preventive therapy, and WHO clinical stages were used to develop risk prediction. The AUROC curve of the original model was 87.53% [95% confidence interval (CI): 83.88-91.25] and the calibration plot ( P -value = 0.51). After internal validation, the AUROC curve of 86.61% (95% CI: 82.92-90.29%) was comparable with the original model, with an optimism coefficient of 0.0096 and good calibration ( P -value = 0.10). Our model revealed excellent sensitivity (92.65%) and negative predictive value (NPV) (98.60%) with very good specificity (70.06%) and accuracy (72.76%). After validation, accuracy (74.85%) and specificity (76.27%) were improved, but sensitivity (86.76%) and NPV (97.66%) were relatively reduced. The risk prediction model had a net benefit up to 7.5 threshold probabilities. This prognostic model had very good performance. Moreover, it had very good sensitivity and excellent NPV. The model could help clinicians use risk estimation and stratification for early diagnosis and treatment to improve patient outcomes and quality of life.

Neutralizing Antibodies Targeting BK Polyomavirus

Abstract The majority of the world’s adult population is latently infected by the BK polyomavirus. It causes asymptomatic infection in healthy individuals but emerged as a threat to kidney transplant recipients because of virus associated nephropathy caused by immunosuppressive therapy. In these conditions, when a functional cellular response is impaired by immunosuppression, neutralizing antibodies may play a major role, since they can directly prevent infection of target cells, independently of cell mediated immunity, by binding to the viral particles. Studying the contribution of anti-BK virus neutralizing antibodies in viral control has long been hampered by the lack of convenient in vitro models but major progress has been made in the last decade. The four BK virus genotypes have been demonstrated to behave as distinct serotypes. A low recipient neutralizing antibody titer against the donor’s serotype before kidney transplant has been significantly associated with BK virus replication after transplant. Different mechanisms exploited by the BK virus to evade neutralizing antibodies have been described. Recent studies also support the potential benefit of administering intravenous immunoglobulins or monoclonal neutralizing antibodies as a therapeutic strategy and, more interestingly, this could also be used as preventive or pre-emptive therapy, before advanced kidney damage has occurred. Besides, neutralizing antibodies could be induced by vaccination. In this review, we summarize accumulated knowledge on anti-BK virus neutralizing antibodies as well as their clinical importance and therapeutic potential for kidney transplant recipients.

Glycoprotein Nonmetastatic Melanoma Protein B: A Potential Therapeutic Target in Chronic Intestinal Fibrosis Induced by Dextran Sulfate Sodium

Abstract Background: Intestinal fibrosis is a complication of inflammatory bowel disease (IBD). Currently, there are no effective preventive measures or medical therapies for intestinal fibrosis. Surgery remains the only available strategy in the management of fibro stenotic enteropathies. However, more than 50% of patients undergoing surgery experience recurrence of stenosis. We assessed effects of glycoprotein nonmetastatic melanoma protein B (Gpnmb) on chronic colonic fibrosis induced by dextran sulfate sodium (DSS) in mice. Materials and Methods: GSE42768 mRNA microarray dataset was selected to carry out GEO2R bioinformatics analysis to predict differentially expressed genes. Chronic colonic inflammation-associated fibrosis was induced by DSS in mice. Twenty-four healthy male BALB/c were assigned to four groups: Control, model, T1: Intragastric administration of Thalidomide (Thal) 100 mg/kg.day beginning at day 18, T2: Intragastric administration of Thal (100 mg/kg.day) beginning at day 0 (n = 6 in each group). The colon was removed after modeling and assessed by pathological staining, Western blot, and reverse-transcription polymerase chain reaction. Col1α2, Gpnmb, Wnt1, and β-catenin antibodies were used. Results: The degree of chronic colitis and fibrosis was highest in the model group, and lowest in the control group. Thal treatment significantly alleviated DSS-induced chronic colitis and intestinal fibrosis, decreasing Gpnmb at both mRNA and Western blot levels. Expressions of Col1α2, Wnt1, and β-catenin got the same results. Conclusions: From bioinformatic analysis and fundamental experiment, we have illustrated that Gpnmb may stimulate the occurrence of intestinal fibrosis via Wnt1/β-catenin pathway. It may be a new therapeutic target for IBD-related intestinal fibrosis.

Glycoprotein Nonmetastatic Melanoma Protein B: A Potential Therapeutic Target in Chronic Intestinal Fibrosis Induced by Dextran Sulfate Sodium

Abstract Background: Intestinal fibrosis is a complication of inflammatory bowel disease (IBD). Currently, there are no effective preventive measures or medical therapies for intestinal fibrosis. Surgery remains the only available strategy in the management of fibro stenotic enteropathies. However, more than 50% of patients undergoing surgery experience recurrence of stenosis. We assessed effects of glycoprotein nonmetastatic melanoma protein B (Gpnmb) on chronic colonic fibrosis induced by dextran sulfate sodium (DSS) in mice. Materials and Methods: GSE42768 mRNA microarray dataset was selected to carry out GEO2R bioinformatics analysis to predict differentially expressed genes. Chronic colonic inflammation-associated fibrosis was induced by DSS in mice. Twenty-four healthy male BALB/c were assigned to four groups: Control, model, T1: Intragastric administration of Thalidomide (Thal) 100 mg/kg.day beginning at day 18, T2: Intragastric administration of Thal (100 mg/kg.day) beginning at day 0 (n = 6 in each group). The colon was removed after modeling and assessed by pathological staining, Western blot, and reverse-transcription polymerase chain reaction. Col1α2, Gpnmb, Wnt1, and β-catenin antibodies were used. Results: The degree of chronic colitis and fibrosis was highest in the model group, and lowest in the control group. Thal treatment significantly alleviated DSS-induced chronic colitis and intestinal fibrosis, decreasing Gpnmb at both mRNA and Western blot levels. Expressions of Col1α2, Wnt1, and β-catenin got the same results. Conclusions: From bioinformatic analysis and fundamental experiment, we have illustrated that Gpnmb may stimulate the occurrence of intestinal fibrosis via Wnt1/β-catenin pathway. It may be a new therapeutic target for IBD-related intestinal fibrosis.

Pharmacokinetics of piperaquine and its association with intermittent malaria preventive therapy outcomes during pregnancy

BackgroundDihydroartemisinin-piperaquine (DHP) recently showed superior effectiveness over sulfadoxine-pyrimethamine for malaria intermittent preventive treatment in pregnancy (IPTp). We investigated day 7 piperaquine pharmacokinetics and its therapeutic efficacy in preventing malaria during pregnancy.MethodsMalaria-free (mRDT) pregnant women (n = 400) who received monthly IPTp-DHP were enrolled and followed till delivery. Day 7 Plasma piperaquine concentrations were determined after each IPTp dose using UPLC/MS/MS. IPTp outcomes (symptomatic malaria and parasitemia during pregnancy, placental malaria, and maternal malaria at delivery) were monitored. Linear mixed model and Cox regression were used to assess predictors of day 7 piperaquine concentration and treatment outcome, respectively.ResultsThe incidences of symptomatic malaria and parasitemia during pregnancy per 100 person-year at risk were 2 and 33, respectively. The prevalence of histopathologically confirmed placental malaria and maternal malaria at delivery were 3% and 9.8%, respectively. Repeated monthly IPTp-DHP resulted in significantly increased day 7 plasma piperaquine concentration (p < 0.001). Following the 1st, 2nd, and 3rd monthly IPTp-DHP doses, the proportions of women with day 7 piperaquine concentration below the therapeutic threshold (< 30 ng/mL) were 6.1%, 4.1% and 3.6%, respectively. Factors such as maternal age, body weight and trimester were not significant predictors of day 7 piperaquine concentration. However, having a low day 7 piperaquine plasma concentration (< 30 ng/mL) was significantly associated with a higher risk of parasitemia during pregnancy (p = 0.004).ConclusionLower day 7 piperaquine plasma concentration is a risk factor for parasitemia during pregnancy. Single plasma sampling at day 7 can be used to monitor piperaquine effectiveness during IPTp-DHP.Trial registrationRegistered 09/12/2016, PACTR201612001901313.

Pharmacokinetics of piperaquine and its association with intermittent malaria preventive therapy outcomes during pregnancy.

Dihydroartemisinin-piperaquine (DHP) recently showed superior effectiveness over sulfadoxine-pyrimethamine for malaria intermittent preventive treatment in pregnancy (IPTp). We investigated day 7 piperaquine pharmacokinetics and its therapeutic efficacy in preventing malaria during pregnancy. Malaria-free (mRDT) pregnant women (n = 400) who received monthly IPTp-DHP were enrolled and followed till delivery. Day 7 Plasma piperaquine concentrations were determined after each IPTp dose using UPLC/MS/MS. IPTp outcomes (symptomatic malaria and parasitemia during pregnancy, placental malaria, and maternal malaria at delivery) were monitored. Linear mixed model and Cox regression were used to assess predictors of day 7 piperaquine concentration and treatment outcome, respectively. The incidences of symptomatic malaria and parasitemia during pregnancy per 100 person-year at risk were 2 and 33, respectively. The prevalence of histopathologically confirmed placental malaria and maternal malaria at delivery were 3% and 9.8%, respectively. Repeated monthly IPTp-DHP resulted in significantly increased day 7 plasma piperaquine concentration (p < 0.001). Following the 1st, 2nd, and 3rd monthly IPTp-DHP doses, the proportions of women with day 7 piperaquine concentration below the therapeutic threshold (< 30 ng/mL) were 6.1%, 4.1% and 3.6%, respectively. Factors such as maternal age, body weight and trimester were not significant predictors of day 7 piperaquine concentration. However, having a low day 7 piperaquine plasma concentration (< 30 ng/mL) was significantly associated with a higher risk of parasitemia during pregnancy (p = 0.004). Lower day 7 piperaquine plasma concentration is a risk factor for parasitemia during pregnancy. Single plasma sampling at day 7 can be used to monitor piperaquine effectiveness during IPTp-DHP. Registered 09/12/2016, PACTR201612001901313.

Comparison of thrombodynamic methods and routine hemostasis tests in the evaluation of hypercoagulable syndrome in chronic glomerulonephritis

Background. Nephrotic syndrome (NS) is associated with a high risk of thrombotic complications. In this group of patients, routine local tests for assessing hemostasis do not accurately reflect hypercoagulable state. Global functional tests for assessing hemostasis, including thrombodynamics (TD), are considered promising for assessing disorders in the blood coagulation system of these patients. Aim. To compare the rate of hypercoagulability according to routine hemostatic tests and TD and to evaluate the factors associated with increased risk of thrombotic complications in patients with chronic glomerulonephritis (CGN). Materials and methods. The study included 94 patients with active CGN who were not receiving anticoagulant therapy; 63 (80.3%) patients had NS, and 31 (19.7%) had active CGN without NS. Hemostasis parameters were assessed using local coagulation tests and TD test. Using logistic regression analysis, factors associated with the risk of thrombosis were assessed. Results. Of the 94 patients with active CGN in 63 without preventive anticoagulant therapy, hypercoagulability according to routine tests was detected in 6 (9.5%) patients with NS and in 3 (9.7%) patients without NS (p0.05). Hypercoagulability according to the TD test was detected in 24 (53.9%) patients with NS and in 5 (32.2%) without NS (p0.05). The formation of spontaneous clots was observed in 29 (30.9%) of patients with CGN, most of them 24 (83%) with NS. 10.6% of patients in our cohort experienced thromboembolic events. The risk of thromboembolic events according to the univariate regression analysis was associated with older age, higher lipid levels, use of glucocorticosteroids and detection of spontaneous clots by the TD test. No association of thromboembolic events with abnormalities in routine hemostasis tests was obtained. Conclusion. In patients with CGN with nephrotic syndrome, hypercoagulability is detected in 9.5% of cases with routine coagulation tests and in 53.9% of cases with TD test. Detection of spontaneous clots by TD test is associated with a risk of thromboembolic events.

Advances in nucleic acid-targeted therapies for cardiovascular disease prevention.

Nucleic acid-based therapies are being rapidly developed for prevention and management of cardiovascular diseases (CVD). Remarkable advancements have been achieved in the delivery, safety, and effectiveness of these therapeutics in the past decade. These therapies can also modulate therapeutic targets that cannot be sufficiently addressed using traditional drugs or antibodies. Among the nucleic acid-targeted therapeutics under development for CVD prevention are RNA-targeted approaches, including antisense oligonucleotides (ASO), small interfering RNAs (siRNA), and novel genome editing techniques. Genetic studies have identified potential therapeutic targets that are suggested to play a causative role in development and progression of CVD. RNA- and DNA-targeted therapeutics can be particularly well delivered to the liver, where atherogenic lipoproteins and angiotensinogen are produced. Lipoproteins currently targeted include proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein A (Apo(a)), apolipoprotein C3 (APOC3), angiopoietin-like 3 (ANGPTL3). Several large-scale clinical development programs for nucleic acid-targeted therapies in cardiovascular prevention are under way, which may also be attractive from a therapy adherence point of view, given the long action of these therapeutics. In addition to genome editing, the concept of gene transfer is presently under assessment in preclinical and clinical investigations as a potential approach for addressing LDL-R deficiency. Furthermore, ongoing research is exploring the use of RNA-targeted therapies to treat arterial hypertension by reducing hepatic angiotensinogen (AGT) production. This review summarizes the rapid translation of siRNA and ASO therapeutics as well as gene editing into clinical studies to treat dyslipidemia and arterial hypertension for CVD prevention. It also outlines potential innovative therapeutic options that are likely relevant to the future of cardiovascular medicine.

Modeling mechanisms of chemotherapy-induced peripheral neuropathy and chemotherapy transport using induced pluripotent stem cell-derived sensory neurons

Backgroundand Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) constitutes a significant health problem due to the increasing prevalence and lack of therapies for treatment and prevention. While pivotal for routine cancer treatment, paclitaxel and vincristine frequently cause CIPN and impact the quality of life among cancer patients and survivors. Here, we investigate molecular mechanisms and drug transport in CIPN. Experimental approachHuman sensory neurons were derived from induced pluripotent stem cells (iPSC-SNs), which were characterized using flow cytometry and immunolabeling. These iPSC-SNs were exposed to different concentrations of the two microtubule-targeting agents, paclitaxel and vincristine, with and without pre-exposure to inhibitors and inducers of efflux transporters. Neuronal networks were quantified via fluorescent staining against sensory neuron markers. Transcriptional effects of the chemotherapeutics were examined using quantitative polymerase chain reactions (qPCR). Key resultsPaclitaxel exposure resulted in axonal retraction and thickening, while vincristine caused fragmentation and abolishment of axons. Both agents increased the mRNA expression of the pain receptor, transient receptor potential vanilloid (TRPV1), and highly induced neuronal damage, as measured by activating transcription factor 3 (ATF3) mRNA. iPSC-SNs express the efflux transporters, P-glycoprotein (P-gp, encoded by ABCB1) and multidrug resistance-associated protein 1 (MPR1, encoded by ABCC1). Modulation of efflux transporters indicate that P-gp and MRP1 play a role in modulating neuronal accumulation and neurotoxicity in preliminary experiments. Conclusionand Implications: iPSC-SNs are a valuable and robust model to study the role of efflux transporters and other mechanistic targets in CIPN. Efflux transporters may play a role in CIPN pathogenesis as they regulate the disposition of chemotherapy to the peripheral nervous system, and they may present potential therapeutic targets for CIPN.

Prolonged and repeated microemboli detection in acute ischemic stroke – The Norwegian Microemboli in Acute Stroke Study (NOR-MASS)

ObjectivesCerebral microemboli can be detected by transcranial Doppler monitoring (TCDM) and may elucidate stroke etiology, the effect of preventive therapy, and the risk of stroke recurrence. Microemboli detection is usually performed for up to 60 minutes, but due to temporal variability, microembolization may be missed if the monitoring time is too short. We aimed to assess the time course of microembolization in acute ischemic stroke and explore the utility of prolonged and repeated microemboli detection. Materials and MethodsPatients with suspected ischemic stroke and symptom onset within 24 hours were examined with bilateral, stationary TCDM for one hour followed by unilateral, ambulatory TCDM for two hours. Unilateral TCDM was repeated for the following two days and after three months. ResultsWe included 47 patients, of which 41 had ischemic stroke, five had transient ischemic attack, and one had amaurosis fugax. Microemboli were detected in 60 % of patients. The occurrence was highest within 24 hours after onset and significantly lower at three months. Prolonged and repeated microemboli detection yielded only one additional microemboli-positive patient. Hence, patients who initially were microemboli negative tended to remain negative. We could not demonstrate an association between microemboli occurrence and clinical outcome or stroke recurrence. ConclusionsMicroembolic signals are frequent within 24 hours after ischemic stroke onset, but prolonged and repeated microemboli detection did not increase the yield of MES positive patients. Clinical Trial Registration-URLhttp://www.clinicaltrials.gov. Unique identifier: NCT03543319.

Role of Dapagliflozin in Prevention of Contrast Induced Nephropathy in Diabetic Patients Undergoing Primary Percutaneous Coronary Intervention

Abstract Background Contrast induced nephropathy (CIN), is a known complication of any coronary intervention regardless the amount of contrast. Studies have shown that patients who develop CIN have a greater risk for death or prolonged hospitalization, as well as for other adverse outcomes, including early or late cardiovascular events especially if after percutaneous coronary intervention (PCI). Research is continuous to find pharmacological interventions to prevent CIN. While many therapies in prevention of CIN have been studied, only good hydration has been proven to be of benefit. This Abstractattempt to provide the role of dapagliflozin in prevention of CIN. Aim and objectives The aim of the study was to study the efficacy of dapagliflozin administration as a preventive tool for Contrast induced nephropathy (CIN), in diabetic patients undergoing primary percutaneous coronary intervention (PCI). Patients and Methods This study included 250 diabetic patients presented to emergency departments of Ain shams university hospitals from July 2021 till June 2022 and diagnosed with STEMI as being defined as Patients with ST elevation myocardial infarction defined as having symptoms of ischemia and ST-segment elevation of at least two contiguous leads with ST-segment elevation ≥ 2.5 mm in men &amp;lt; 40 years, ≥2 mm in men ≥ 40 years, or ≥ 1.5 mm in women in leads V2 – V3 and/or ≥ 1 mm in the other leads 1, that had been revascularized by primary PCI as per the recommendations of The European society of cardiology guidelines for diagnosis and management of ST elevation myocardial infarction published in 2017. CIN was defined by renal function impairment after IV contrast as mirrored by an absolute increase by 0.5mg/dL (or greater) or relative increase by 25% (or greater) of baseline serum creatinine over 48 hours or, better, by a decrease by 25% in the estimated glomerular filtration rate (eGFR(. The patients were randomized using dedicated software programme into two groups. Study group including 125 patients was the dapagliflozin group. Control group including 125 patients was the standard control group. Results Our study had demonstrated that a higher proportion of patients developed CIN in the control group (21 (16.8%)) vs (13 (10.4%)) in the study group (dapagliflozin group) but it didn’t reach a statistically significant difference with P-value =0.139. Conclusion Dapagliflozin failed to prove any statistically significant prevention against CIN.

Initiation of lipid-lowering therapy as primary prevention of cardiovascular disease in the elderly.

This study aimed to analyse the initiation adherence phase to lipid-lowering therapy for primary prevention of cardiovascular disease in a Spanish population aged 70 years or older. The secondary objective was to identify the determinants of initiation and early discontinuation. This was an observational study conducted in the CArdiovascular Risk factors for HEalth Service research (CARhES) cohort. People aged 70 and older with a first prescription of a lipid-lowering drug and without a previous major adverse cardiovascular event (MACE) were selected (2018-2021). Data on sociodemographics, clinical conditions, drugs and use of health services were collected from clinical and administrative electronic databases. The study population was classified into: non-initiation, early discontinuation (i.e., discontinuation after the first dispensing) and initiation with more than one dispensing. Their characteristics were compared. Determinants of initiation and early discontinuation were explored. Among the 15 019 people studied, 80.2% initiated the medication, 11.2% showed an early discontinuation and 8.6% were non-initiators. An older age or conditions such as dementia, diabetes or depression reduced the likelihood of initiation, while obesity and a high pharmacological burden increased it. People over 90 years of age or those prescribed a statin in combination were more likely to have an early discontinuation. Non-initiation and early discontinuation are common among older people prescribed lipid-lowering drugs as primary prevention of cardiovascular disease for the first time. The presence of chronic pathologies other than cardiovascular ones should be considered when assessing whether or not to prescribe these drugs in the elderly.

Oral anticoagulation with Edoxaban for stroke prevention in patients with atrial fibrillation: Analysis of 1-year follow-up data of routine clinical practice in Germany, Austria and Switzerland (DACH) from the ETNA-AF registry

Non-vitamin-K oral anticoagulants (NOACs) are safe and effective for stroke prevention in patients with atrial fibrillation (AF). Data on the safety and efficacy of Edoxaban in routine care in Germany, Austria and Switzerland (DACH) are limited. We report one-year outcomes in patients with AF treated with Edoxaban in routine care. The ETNA-AF-Europe study (Clinicaltrials.gov:NCT02 944 019) is a multicenter, prospective, observational study that enrolled 13 092 patients with AF treated with Edoxaban from 852 sites across 10 European countries (Austria, Belgium, Germany, Ireland, Italy, the Netherlands, Portugal, Spain, Switzerland, and the United Kingdom). The DACH-cohort consists of 5457 (41,7 %) patients of sites in Germany, Austria and Switzerland. Patients had a mean age of 74 years (2384 [44 %]women) and a mean CHA2DS2-VASc-score of 3.2 ± 1.4. A label-conform dosing of Edoxaban was administered to 4309 patients (78,9 %). At the one-year-follow-up a stroke or systemic embolism occurred in 42 patients (0,8 %/year), and severe bleeding was reported in 36 patients (0,7 %/year). Ten patients (0,2 %/year) suffered intracranial and 13 patients (0,3 %/year)gastrointestinal bleeding. Numbers of death from all causes and cardiovascular death occurred in 179 patients (3,4 %/year) and 85 patients (1,6 %/year), respectively. Age > 75 years, frailty and a CHA2DS2-VASc score ≥ 4 were associated with a higher all-cause mortality - and those patients were more likely to suffer a stroke or a major bleeding event. In Germany, Austria and Switzerland in patients with AF on Edoxaban therapy for stroke prevention the number of stroke and major bleeding events is low. Increasing morbidity is associated with a higher number of important clinical events.

Optimizing the cascade of prevention to protect people from tuberculosis: A potential game changer for reducing global tuberculosis incidence.

The provision of tuberculosis preventive treatment is one of the critical interventions to reduce tuberculosis incidence and ultimately eliminate the disease, yet we still miss appropriate tools for an impactful intervention and treatment coverage remains low. We used recent data, epidemiological estimates, and research findings to analyze the challenges of each step of the cascade of tuberculosis prevention that currently delay the strategy implementation. We addressed research gaps and implementation bottlenecks that withhold key actions in tuberculosis case finding, testing for tuberculosis infection, provision of preventive treatment with safer, shorter regimens and supporting people to complete their treatment. Empowering communities to generate demand for preventive therapy and other prevention services in a holistic manner and providing adequate financial support to sustain implementation are essential requirements. The adoption of an effective, universal monitoring and evaluation system is a prerequisite to provide general and granular insight, and to steer progress of the tuberculosis infection strategy at global and local level.

Strategies for isoniazid preventive therapy in HIV-positive patients who consume alcohol.

<sec><title>BACKGROUND</title>WHO guidance to defer isoniazid preventive therapy (IPT) among those with regular alcohol use because of hepatotoxicity concerns may exclude many people living with HIV (PLWH) at high TB risk in these settings.</sec><sec><title>OBJECTIVE</title>To evaluate hepatotoxicity during TB preventive therapy (TPT) in PLWH who report alcohol use in Uganda over 10 years.</sec><sec><title>METHODS</title>We developed a Markov model of latent TB infection, isoniazid preventive therapy (IPT - a type of TPT), and TB disease using data from the Alcohol Drinkers' Exposure to Preventive Therapy for TB (ADEPTT) study. We modeled several treatment scenarios, including no IPT, IPT with liver enzyme monitoring (AST/ALT) during treatment, and IPT with pre-screening using the tuberculin skin test (TST).</sec><sec><title>RESULTS</title>The no IPT scenario had 230 TB deaths/100,000 population over 10 years, which is more than that seen in any IPT scenario. IPT, even with no monitoring, was preferred over no IPT when population TB disease incidence was >50 in 100,000.</sec><sec><title>CONCLUSIONS</title>For PLWH who report alcohol use in high TB burden settings, IPT should be offered, ideally with regular AST/ALT monitoring. However, even if regular monitoring is not possible, IPT is still preferable to no IPT in almost every modeled scenario.</sec>.

Rationale and Design of SCOT-HEART 2Trial: CT Angiography for the Prevention of Myocardial Infarction.

Coronary artery disease continues to be the leading cause of death globally. Identifying patients who are at risk of coronary artery disease remains a public health priority. At present, the focus of cardiovascular disease prevention relies heavily on probabilistic risk scoring despite no randomized controlled trials demonstrating their efficacy. The concept of using imaging to guide preventative therapy is not new, but has previously focused on indirect measures such as carotid intima-media thickening or coronary artery calcification. In recent trials, patients found to have coronary artery disease on computed tomography (CT) coronary angiography were more likely to be started on preventative therapy and had lower rates of cardiac events. This led to the design of the SCOT-HEART 2 (Scottish Computed Tomography of the Heart 2) trial, which aims to determine whether screening with the use of CT coronary angiography is more clinically effective than cardiovascular risk scoring to guide the use of primary preventative therapies and reduce the risk of myocardial infarction.

Being highly sensitive person negatively impacts on cognitive and psychosocial fatigue in multiple sclerosis patients: a cross-sectional, monocenter study

BackgroundFatigue is a common symptom in Multiple Sclerosis (MS), but its determinants are not clarified yet. Sensory processing sensitivity (SPS) is a personality trait characterized by enhanced sensitivity towards endogenous and exogenous stimuli, and higher attention toward minimal stimuli, resulting in overarousal and fatigue. Objectiveto evaluate the association between SPS and fatigue in MS patients. Methods192 consecutive MS patients (age of 43.3 ± 12.1 years; females 67.2%; median EDSS of 2.5 (0 – 7)) underwent clinical (EDSS, age, gender), cognitive (BICAMS, Trial Making Test [TMT]), psychosocial (Beck Anxiety Inventory [BAI], Beck Depression Inventory [BDI], Modified Fatigue Impact Scale [MFIS]) and sensitivity evaluation (Highly Sensitive Person [HSP]Scale). Patients were classified as HSP if the score was greater than 14. A stepwise regression model was applied to explore association between SPS and MFIS total scores and sub-scores, by accounting for age, gender, education, EDSS, Cerebral FS scores, TMT-Part A and part B scores, BAI, BDI, and Pittsburgh Sleep Quality Index (PSQI). ResultsTotal HSP was 17.2 ± 6.8 and 129 patients (67%) were classified as highly sensitive persons (HSP). HSP patients were more female patients (p=0.02) with a longer disease duration (p=0.03). HSP people showed higher total MFIS score (27.6 ± 20.6 vs 13.2 ± 14.1, p<0.001), higher physical MFIS score (p<0.001), higher cognitive MFIS score (p<0.001), higher psychosocial MFIS score (p<0.001) vs non-HSP patients. Higher total MFIS was associated with SPS trait (coeff. 6.9, p=0.006). Specifically, SPS trait was associated with higher cognitive MFIS (coeff. 5.3, p<0.001) and higher psychosocial MFIS (coeff. 0.7, p=0.02). ConclusionSPS was associated with fatigue. Since SPS could be easily and quickly assessed in clinical settings, SPS could unveil a higher propensity of a patient toward fatigue occurrence over the disease course and could provide hints for possible preventive cognitive behaviour therapy.

Astounding the anxiolytic and eudemonic potential of certain fruits

Anxiety is a state of mind with some fear that affects physical health by disrupting neurotransmission and hormonal control. Both diet (inadequate and unhealthy dietary patterns) and environment (social and financial factors) trigger its progression; therefore, diet is considered to have a significant involvement in its prevention or adjunct therapy. A unique nutrient profile and bioactive ingredients are seen in fruits to provide health outcomes beyond nutritive properties. The relaxing potential of such fruits is attributed to the functional nature and therapeutic ingredients i.e., catecholamines, myricetin, quercetin, betalains, etc. that enhance the efficiency of hormones, neurotransmitters, and metabolic pathways. This review presented certain fruits having positive associations with mental health and anxiety amelioration. Various types of research evidenced the anxiolytic effect of certain fruits through clinical trials. Among them, berries, opuntia, and black pepper also have shown anxiety-relieving effects in clinical studies by restoring antioxidant enzymes, hormonal modulations, and managing neurotransmitters. Citrus species are loaded with flavonoids which are involved in the expression of GABA (Gamma-Amino Butyric Acid) to calm the nervous system. Some other fruits also potentiate memory and cognition when taken in ample amounts owing to their secondary metabolites. Thus, the incorporation of such fruits into a regular diet has been found to have a significant impact on mental well-being and brain health.