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Giornale Italiano Di Nefrologia :... Jun 2024Peritoneal dialysis stands as an established form of renal replacement therapy; yet peritonitis remains a major complication associated with it. This study, analyzing... (Observational Study)
Observational Study
Peritoneal dialysis stands as an established form of renal replacement therapy; yet peritonitis remains a major complication associated with it. This study, analyzing two decades of data from the Nephrology, Dialysis, and Hypertension Division of the University-Hospital IRCCS in Bologna, aimed to identify prognostic factors linked to peritonitis events. It also sought to evaluate the suitability of different peritoneal dialysis techniques, with a focus on Automated Peritoneal Dialysis (APD) and Continuous Ambulatory Peritoneal Dialysis (CAPD). Additionally, the study assessed the impact of an educational program introduced in 2005 on peritonitis frequency. Conducting an observational, retrospective, single-center study, 323 patients were included in the analysis, categorized based on their use of APD or CAPD. Despite widespread APD usage, no significant correlation was found between the dialysis technique (APD or CAPD) and peritonitis onset. The analysis of the educational program's impact revealed no significant differences in peritonitis occurrence. However, a clear relationship emerged between regular patient monitoring at the reference center and the duration of peritoneal dialysis. Despite the absence of a distinct association between peritonitis onset and dialysis technique, regular patient monitoring at the reference center significantly correlated with prolonged peritoneal dialysis duration.
Topics: Humans; Retrospective Studies; Peritonitis; Prognosis; Peritoneal Dialysis; Male; Female; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Aged
PubMed: 38943332
DOI: No ID Found -
European Journal of Pain (London,... Jun 2024Differential target multiplexed spinal cord stimulation (DTM SCS) was shown to be superior to conventional SCS for treating chronic low back pain (CLBP) in subjects with...
European randomized controlled trial evaluating differential target multiplexed spinal cord stimulation and conventional medical management in subjects with persistent back pain ineligible for spine surgery: 24-month results.
BACKGROUND
Differential target multiplexed spinal cord stimulation (DTM SCS) was shown to be superior to conventional SCS for treating chronic low back pain (CLBP) in subjects with persistent spinal pain syndrome with previous spinal surgery (PSPS-T2) or ineligible for it (PSPS-T1). This study reports 24-month efficacy and safety of DTM SCS vs. conventional medical management (CMM) in PSPS-T1 subjects across four European countries.
METHODS
This is a prospective, multicenter, open-label, randomized, controlled trial with optional crossover. Subjects randomized 1:1 to DTM SCS or CMM. Primary endpoint was responder rate (% subjects reporting ≥50% CLBP relief) at 6 months. A superiority test compared responder rates between treatments. CLBP and leg pain levels, functional disability, quality of life (QoL), patient satisfaction and global impression of change were evaluated for 24 months. A Composite Responder Index (CRI) was obtained using CLBP relief, disability and QoL. Incidence of study-related adverse events evaluated safety.
RESULTS
A total of 55 and 57 subjects were randomized to DTM SCS and CMM respectively. DTM SCS was superior, with CLBP responder rates ≥80% and CLBP relief >5.6 cm (>70% reduction) through the 24-month follow-up. Improvements with DTM SCS in other outcomes were sustained. The CRI was >80% for DTM SCS through 24 months. Opioid medication intake decreased in subjects treated with DTM SCS. Most patients treated with DTM SCS felt satisfied and improved at the end of the study. Safety was congruent with other studies.
CONCLUSION
DTM SCS is efficacious and safe during 24 months for the treatment of CLBP and leg pain in PSPS-T1 patients ineligible for spine surgery.
SIGNIFICANCE STATEMENT
This randomized controlled trial shows that Differential Target Multiplexed SCS (DTM SCS) is an effective and safe long-term treatment for PSPS type 1 patients suffering from axial low back pain with or without leg pain and who are ineligible for spinal surgery. Currently, CMM treatments are their only option and provide limited benefits. Besides superior pain relief, DTM SCS provides significant improvements in functional disability, quality of life, high levels of satisfaction and perceived impression of change.
PubMed: 38943239
DOI: 10.1002/ejp.2306 -
ESC Heart Failure Jun 2024Inflammation has emerged as a potential key pathophysiological mechanism in heart failure (HF) in general and acute HF (AHF) specifically, with inflammatory biomarkers...
AIMS
Inflammation has emerged as a potential key pathophysiological mechanism in heart failure (HF) in general and acute HF (AHF) specifically, with inflammatory biomarkers shown to be highly predictive of adverse outcomes in these patients. The CORTAHF study builds on both these data and the fact that steroid burst therapy has been shown to be effective in the treatment of respiratory diseases and COVID-19. Our hypothesis is that in patients with AHF and elevated C-reactive protein (CRP) levels without symptoms or signs of infection, a 7-day course of steroid therapy will lead to reduced inflammation and short-term improvement in quality of life and a reduced risk of worsening HF (WHF) events.
METHODS AND RESULTS
The study, which is currently ongoing, will include 100 patients with AHF ages 18-85, regardless of ejection fraction, screened within 12 h of presentation. Patients will be included who have NT-proBNP > 1500 pg/mL and CRP > 20 mg/L at screening. Exclusion criteria include haemodynamic instability and symptoms and signs of infection. After signed consent, eligible patients will be randomized according to a central randomization scheme stratified by centre 1:1 to either treatment once daily for 7 days with 40 mg prednisone orally or to standard care. Patients will be assessed at study day 2, day 4 or at discharge if earlier, and at days 7 and 31 at the hospital; and at day 91 through a telephone follow-up. The primary endpoint is the change in CRP level from baseline to day 7, estimated from a mixed model for repeated measures (MMRM) including all measured timepoints, in patients without a major protocol violation. Secondary endpoints include the time to the first event of WHF adverse event, readmission for HF, or death through day 91; and changes to day 7 in EQ-5D visual analogue scale score and utility index. Additional clinical and laboratory measures will be assessed.
CONCLUSIONS
The results of the study will add to the knowledge of the role of inflammation in AHF and potentially inform the design of larger studies with possibly longer duration of anti-inflammatory therapies in AHF.
PubMed: 38943232
DOI: 10.1002/ehf2.14930 -
Acta Obstetricia Et Gynecologica... Jun 2024Women with systemic lupus erythematosus (SLE) have a higher risk for fetal and maternal complications. We aimed to investigate maternal and fetal complications in...
INTRODUCTION
Women with systemic lupus erythematosus (SLE) have a higher risk for fetal and maternal complications. We aimed to investigate maternal and fetal complications in pregnant women with SLE compared to a high-risk pregnancy cohort (HR) from a tertiary university center and a standard-risk general population (SR) from the Austrian Birth Registry.
MATERIAL AND METHODS
In this retrospective data analysis, we compared the incidence of fetal/neonatal and maternal complications of pregnancies and deliveries of women with SLE to age, body mass index and delivery date-matched high-risk pregnancies from the same department, a progressive tertiary obstetric center and to a group of women, who represent pregnancies with standard obstetric risk from the Austrian Birth Registry.
RESULTS
One hundred women with SLE were compared to 300 women with high-risk pregnancies and 207 039 women with standard-risk pregnancies. The incidence of composite maternal complications (preeclampsia, Hemolysis, Elevated Liver enzymes and Low Platelets [HELLP] syndrome, pregnancy-related hypertension, gestational diabetes mellitus, maternal death, thromboembolic events) was significantly higher in the SLE as compared to the SR group (28% vs. 6.28% SLE vs. SR, p = 0.001). There was no difference between the SLE and the HR groups (28% vs. 29.6% SLE vs. HR group, p = 0.80). The incidence of composite fetal complications (preterm birth before 37 weeks of gestation, stillbirths, birth weight less than 2500 g, fetal growth restriction, large for gestational age, admission to neonatal intensive care unit, 5-min Apgar <7) was also higher in the SLE than in the SR group (55% vs. 25.54% SLE vs. SR p < 0.001) while the higher incidence of adverse fetal outcome was detected in the HR than in the SLE group (55% vs. 75% SLE vs. HR group, p = 0.0005).
CONCLUSIONS
Although composite fetal risk is higher in the SLE group than in the general population, it is still significantly lower as compared to high-risk pregnant women at a tertiary obstetric center. Prepregnancy counseling of women with SLE should put fetal and maternal risk in perspective, not only in relation to healthy, low risk cohorts, but also compared to mixed HR populations.
PubMed: 38943224
DOI: 10.1111/aogs.14880 -
Parasites & Vectors Jun 2024Reliance on praziquantel for the treatment and control of schistosomiasis is likely to facilitate the emergence of drug resistance. Combination therapy targeting adult... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of single-dose artesunate plus sulfalene/pyrimethamine combined with praziquantel for the treatment of children with Schistosoma mansoni or Schistosoma haematobium in western Kenya: a randomised, open-label controlled trial.
BACKGROUND
Reliance on praziquantel for the treatment and control of schistosomiasis is likely to facilitate the emergence of drug resistance. Combination therapy targeting adult and juvenile schistosome worms is urgently needed to improve praziquantel efficacy and delay the potential development of drug resistance. We assessed the efficacy and safety of single-dose praziquantel combined with single-dose artesunate plus sulfalene-pyrimethamine in the treatment of Kenyan children with schistosomiasis.
METHODS
This was an open-label, randomised clinical trial involving 426 school-aged children (7-15 years old) diagnosed with Schistosoma mansoni (by Kato-Katz) or S. haematobium (by urine filtration). They were randomly assigned (1:1:1) to receive a single dose of praziquantel (40 mg/kg), a single dose of artesunate plus sulfalene-pyrimethamine (12 mg/kg artesunate) or combination therapy using a single dose of praziquantel (40 mg/kg) combined with a single dose of artesunate plus sulfalene-pyrimethamine (12 mg/kg artesunate). The primary outcome was cure and egg reduction rates at 6 weeks post-treatment in the available case population. Adverse events were assessed within 3 h after treatment.
RESULTS
Of the 426 children enrolled, 135 received praziquantel, 150 received artesunate plus sulfalene-pyrimethamine, and 141 received combination therapy. Outcome data were available for 348 (81.7%) children. For S. mansoni-infected children (n = 335), the cure rates were 75.6%, 60.7%, and 77.8%, and the egg reduction rates were 80.1%, 85.0%, and 88.4% for praziquantel, artesunate plus sulfalene-pyrimethamine, and combination therapy, respectively. For S. haematobium-infected children (n = 145), the corresponding cure rates were 81.4%, 71.1%, and 82.2%, and the egg reduction rates were 95.6%, 97.1%, and 97.7%, respectively. Seventy-one (16.7%) children reported mild-intensity adverse events. The drugs were well tolerated and no serious adverse events were reported.
CONCLUSIONS
A single oral dose of praziquantel combined with artesunate plus sulfalene-pyrimethamine cured a high proportion of children with S. haematobium but did not significantly improve the treatment efficacy for either urinary or intestinal schistosomiasis. Sequential administration of praziquantel and artesunate plus sulfalene-pyrimethamine may enhance the efficacy and safety outcomes.
Topics: Humans; Child; Praziquantel; Pyrimethamine; Animals; Adolescent; Artesunate; Female; Male; Schistosomiasis mansoni; Schistosoma haematobium; Schistosomiasis haematobia; Schistosoma mansoni; Drug Therapy, Combination; Kenya; Artemisinins; Treatment Outcome; Anthelmintics; Sulfalene; Drug Combinations; Parasite Egg Count
PubMed: 38943214
DOI: 10.1186/s13071-024-06359-6 -
Trials Jun 2024Acute leukaemias (AL) are life-threatening blood cancers that can be potentially cured with treatment involving myelosuppressive, multiagent, intensive chemotherapy...
Biomarker Driven Antifungal Stewardship (BioDriveAFS) in acute leukaemia-a multi-centre randomised controlled trial to assess clinical and cost effectiveness: a study protocol for a randomised controlled trial.
BACKGROUND
Acute leukaemias (AL) are life-threatening blood cancers that can be potentially cured with treatment involving myelosuppressive, multiagent, intensive chemotherapy (IC). However, such treatment is associated with a risk of serious infection, in particular invasive fungal infection (IFI) associated with prolonged neutropenia. Current practice guidelines recommend primary antifungal (AF) prophylaxis to be administered to high-risk patients to reduce IFI incidence. AFs are also used empirically to manage prolonged neutropenic fever. Current strategies lead to substantial overuse of AFs. Galactomannan (GM) and β-D-glucan (BG) biomarkers are also used to diagnose IFI. Combining both biomarkers may enhance the predictability of IFI compared to administering each test alone. Currently, no large-scale randomised controlled trial (RCT) has directly compared a biomarker-based diagnostic screening strategy without AF prophylaxis to AF prophylaxis (without systematic biomarker testing).
METHODS
BioDriveAFS is a multicentre, parallel, two-arm RCT of 404 participants from UK NHS Haematology departments. Participants will be allocated on a 1:1 basis to receive either a biomarker-based antifungal stewardship (AFS) strategy, or a prophylactic AF strategy, which includes existing standard of care (SoC). The co-primary outcomes will be AF exposure in the 12-month post randomisation and the patient-reported EQ-5D-5L measured at 12-month post randomisation. Secondary outcomes will include total AF exposure, probable/proven IFI, survival (all-cause mortality and IFI mortality), IFI treatment outcome, AF-associated adverse effects/events/complications, resource use, episodes of neutropenic fever requiring hospital admission or outpatient management, AF resistance in fungi (non-invasive and invasive) and a Desirability of Outcome Ranking. The trial will have an internal pilot phase during the first 9 months. A mixed methods process evaluation will be integrated in parallel to the internal pilot phase and full trial, aiming to robustly assess how the intervention is delivered. Cost-effectiveness analysis will also be performed.
DISCUSSION
The BioDriveAFS trial aims to further the knowledge of strategies that will safely optimise AF use through comparison of the clinical and cost-effectiveness of a biomarker-led diagnostic strategy versus prophylactic AF to prevent and manage IFI within acute leukaemia. The evidence generated from the study will help inform global clinical practice and approaches within antifungal stewardship.
TRIAL REGISTRATION
ISRCTN11633399. Registered 24/06/2022.
Topics: Humans; Antifungal Agents; Cost-Benefit Analysis; Randomized Controlled Trials as Topic; Invasive Fungal Infections; Multicenter Studies as Topic; Biomarkers; Galactose; Mannans; Treatment Outcome; beta-Glucans; Antimicrobial Stewardship; Leukemia; Time Factors; Cost-Effectiveness Analysis
PubMed: 38943201
DOI: 10.1186/s13063-024-08272-w -
Journal of Cardiothoracic Surgery Jun 2024There is limited data on the 2-year outcomes of transapical transcatheter edge-to-edge repair (TA-TEER) using the ValveClamp in patients with severe primary mitral...
BACKGROUND
There is limited data on the 2-year outcomes of transapical transcatheter edge-to-edge repair (TA-TEER) using the ValveClamp in patients with severe primary mitral regurgitation (MR) and its impact on myocardial deformation.
METHODS
From July 2018 to March 2021, 53 patients with symptomatic severe primary MR underwent TA-TEER were enrolled. The endpoint was the composite of all-cause mortality, recurrent 3 + or 4 + MR, or need for mitral surgery.
RESULTS
Among the 53 patients who had successfully ValveClamp implantation, 8(15.1%) reached the composite endpoint. Significant improvement in left ventricular (LV) end-diastolic volume, pulmonary artery systolic pressure, NYHA functional class, and MR severity were observed (P < 0.05 for all). Univariate Cox's regression analysis revealed that LV end-diastolic volume index, LV end-systolic volume index, left atrial volume index, and pulmonary artery systolic pressure were associated with adverse events (P < 0.05 for all). On multivariate Cox regression analysis, left atrial volume index was independently associated with the endpoint (hazard ratio, 1.049; 95% CI, 1.009-1.091; P < 0.001) after adjustment for above echocardiographic parameters. LV global longitudinal strain and apical longitudinal strain in global and regional segments decreased at 30 days, but showed a recovery at 2 years with no significant difference compared to the baseline.
CONCLUSION
TA-TEER using the ValveClamp presented favorable safety and efficacy at 2-year. Myocardial deformation impairment was observed at 30 days post-procedure, but did not persist at 2 years.
Topics: Humans; Mitral Valve Insufficiency; Male; Female; Aged; Mitral Valve; Middle Aged; Heart Valve Prosthesis Implantation; Treatment Outcome; Echocardiography; Retrospective Studies; Cardiac Catheterization
PubMed: 38943166
DOI: 10.1186/s13019-024-02827-3 -
BMC Infectious Diseases Jun 2024Intravenous fosfomycin (IVFOF) is gaining interest in severe infections. Its use may be limited by adverse events (AEs). Little experience exists on IVFOF therapeutic...
BACKGROUND
Intravenous fosfomycin (IVFOF) is gaining interest in severe infections. Its use may be limited by adverse events (AEs). Little experience exists on IVFOF therapeutic drug monitoring (TDM) in real-life setting.
PATIENTS AND METHODS
Retrospective study of patients receiving IVFOF for > 48 h at Policlinico Hospital (Milan, Italy) from 01/01/2019 to 01/01/2023. AEs associated to IVFOF graded CTCAE ≥ II were considered. Demographic and clinical risk factors for IVFOF-related AEs were analysed with simple and multivariable regression models. The determination of IVFOF TDM was made by a rapid ultraperformance liquid chromatography mass spectrometry method (LC-MS/MS) on plasma samples. The performance of TDM (trough levels (Cmin) in intermittent infusion, steady state levels (Css) in continuous infusion) in predicting AEs ≤ 5 days after its assessment was evaluated.
RESULTS
Two hundred and twenty-four patients were included. At IVFOF initiation, 81/224 (36.2%) patients were in ICU and 35/224 (15.7%) had septic shock. The most frequent infection site was the low respiratory tract (124/224, 55.4%). Ninety-five patients (42.4%) experienced ≥ 1AEs, with median time of 4.0 (2.0-7.0) days from IVFOF initiation. Hypernatremia was the most frequent AE (53/224, 23.7%). Therapy discontinuation due to AEs occurred in 38/224 (17.0%). ICU setting, low respiratory tract infections and septic shock resulted associated with AEs (RR 1.59 (95%CI:1.09-2.31), 1.46 (95%CI:1.03-2.07) and 1.73 (95%CI:1.27-2.37), respectively), while IVFOF daily dose did not. Of the 68 patients undergone IVFOF TDM, TDM values predicted overall AEs and hypernatremia with AUROC of 0.65 (95%CI:0.44-0.86) and 0.91 (95%CI:0.79-1.0) respectively for Cmin, 0.67 (95%CI:0.39-0.95) and 0.76 (95%CI:0.52-1.0) respectively for Css.
CONCLUSIONS
We provided real world data on the use of IVFOF-based regimens and associated AEs. IVFOF TDM deserves further research as it may represent a valid tool to predict AEs.
KEY POINTS
Real world data on intravenous fosfomycin for severe bacterial infections. AEs occurred in over 40% (therapy discontinuation in 17%) and were related to baseline clinical severity but not to fosfomycin dose. TDM showed promising results in predicting AEs.
Topics: Humans; Fosfomycin; Female; Male; Retrospective Studies; Anti-Bacterial Agents; Middle Aged; Drug Monitoring; Risk Factors; Aged; Administration, Intravenous; Italy; Adult; Tandem Mass Spectrometry
PubMed: 38943088
DOI: 10.1186/s12879-024-09541-4 -
BMC Cardiovascular Disorders Jun 2024Pulmonary transit time (PTT) can be measured automatically from arterial input function (AIF) images of dual sequence first-pass perfusion imaging. PTT has been...
BACKGROUND
Pulmonary transit time (PTT) can be measured automatically from arterial input function (AIF) images of dual sequence first-pass perfusion imaging. PTT has been validated against invasive cardiac catheterisation correlating with both cardiac output and left ventricular filling pressure (both important prognostic markers in heart failure). We hypothesized that prolonged PTT is associated with clinical outcomes in patients with heart failure.
METHODS
We recruited outpatients with a recent diagnosis of non-ischaemic heart failure with left ventricular ejection fraction (LVEF) < 50% on referral echocardiogram. Patients were followed up by a review of medical records for major adverse cardiovascular events (MACE) defined as all-cause mortality, heart failure hospitalization, ventricular arrhythmia, stroke or myocardial infarction. PTT was measured automatically from low-resolution AIF dynamic series of both the LV and RV during rest perfusion imaging, and the PTT was measured as the time (in seconds) between the centroid of the left (LV) and right ventricle (RV) indicator dilution curves.
RESULTS
Patients (N = 294) were followed-up for median 2.0 years during which 37 patients (12.6%) had at least one MACE event. On univariate Cox regression analysis there was a significant association between PTT and MACE (Hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.08-1.25, P = 0.0001). There was also significant association between PTT and heart failure hospitalisation (HR 1.15, 95% CI 1.02-1.29, P = 0.02) and moderate correlation between PTT and N-terminal pro B-type natriuretic peptide (NT-proBNP, r = 0.51, P < 0.001). PTT remained predictive of MACE after adjustment for clinical and imaging factors but was no longer significant once adjusted for NT-proBNP.
CONCLUSIONS
PTT measured automatically during CMR perfusion imaging in patients with recent onset non-ischaemic heart failure is predictive of MACE and in particular heart failure hospitalisation. PTT derived in this way may be a non-invasive marker of haemodynamic congestion in heart failure and future studies are required to establish if prolonged PTT identifies those who may warrant closer follow-up or medicine optimisation to reduce the risk of future adverse events.
Topics: Humans; Heart Failure; Male; Female; Middle Aged; Aged; Predictive Value of Tests; Time Factors; Prognosis; Ventricular Function, Left; Myocardial Perfusion Imaging; Stroke Volume; Risk Factors; Pulmonary Circulation; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Artery; Risk Assessment; Ventricular Function, Right; Magnetic Resonance Imaging
PubMed: 38943084
DOI: 10.1186/s12872-024-04003-w -
Nature Medicine Jun 2024There are more than 10,000 individual rare diseases and most are without therapy. Personalized genetic therapy represents one promising approach for their treatment. We...
There are more than 10,000 individual rare diseases and most are without therapy. Personalized genetic therapy represents one promising approach for their treatment. We present a road map for individualized treatment of an ultra-rare disease by establishing a gene replacement therapy developed for a single patient with hereditary spastic paraplegia type 50 (SPG50). Through a multicenter collaboration, an adeno-associated virus-based gene therapy product carrying the AP4M1 gene was created and successfully administered intrathecally to a 4-year-old patient within 3 years of diagnosis as part of a single-patient phase 1 trial. Primary endpoints were safety and tolerability, and secondary endpoints evaluated efficacy. At 12 months after dosing, the therapy was well tolerated. No serious adverse events were observed, with minor events, including transient neutropenia and Clostridioides difficile gastroenteritis, experienced but resolved. Preliminary efficacy measures suggest a stabilization of the disease course. Longer follow-up is needed to confirm the safety and provide additional insights on the efficacy of the therapy. Overall, this report supports the safety of gene therapy for SPG50 and provides insights into precision therapy development for rare diseases. Clinical trial registration: NCT06069687 .
PubMed: 38942994
DOI: 10.1038/s41591-024-03078-4