Optimal Duration Of Treatment Research Articles

Multifocal Soft Contact Lenses for the Treatment of Myopia Progression in Children: A Report by the American Academy of Ophthalmology.

To review the published literature assessing the efficacy of multifocal soft contact lenses for the treatment of myopia progression in children 18 years of age and younger. A literature search of the PubMed database was conducted last in March 2024 and was limited to articles published in English without date restrictions. The search yielded 76 articles, which were reviewed by the primary author in abstract form, and 28 articles were selected for full-text review. Twelve articles were deemed to have met the inclusion criteria and were assigned a level of evidence rating by the panel methodologist. Eleven studies were rated level I and 1 study was rated level II. All studies showed less myopic progression, with changes in spherical equivalent (SE) ranging from 0.22 to 0.81 diopters (D) for multifocal soft contact lenses compared with 0.50 to 1.45 D in control groups who used single-vision spectacles or single-vision contact lenses over the course of at least 1 year. Additionally, axial elongation was less in the multifocal soft contact lens group compared with control groups, with a change in axial length (AL) of 0.05 to 0.39 mm in treatment groups compared with 0.17 to 0.67 mm in control groups with at least 1 year of follow-up. The difference in change between the groups was clinically modest and statistically significant in 11 studies for SE and in all 12 studies for AL. No serious adverse events were reported in any of the studies. Level 1 evidence supports slower myopia progression and AL elongation in children who used multifocal soft contact lenses compared with spectacles or single-vision contact lenses over at least 1 year of follow-up. However, few data are available on optimal treatment duration, the progression over longer periods, or progression after discontinuation of the multifocal contact lenses. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The optimal treatment duration for inspiratory muscle strengthening exercises in stroke patients: a double-blinded randomized controlled trial

ABSTRACT Background Little is known about the ideal duration of inspiratory muscle training in stroke patients. Objective The aim of this study was to assess the effects of short-term and long-term inspiratory muscle strengthening exercises in stroke patients. Methods This study was a prospective, double-blind, randomized controlled trial involving 50 stroke patients. Based on baseline maximum inspiratory pressure (MIP) values, participants were divided into two strata: those with severely weak inspiratory muscle (stratum A) and those with moderately weak inspiratory muscle (stratum B). Within each stratum, individuals were randomly assigned to either the 4-week exercise group, the 8-week exercise group, or the sham group. The exercise groups underwent inspiratory muscle strengthening exercises. The MIP, 6-minute walk test (6MWT), and the Nottingham Extended Activities of Daily Living (NEADL) Index were assessed at baseline, 8, 12, and 24 weeks. Results Subjects in Stratum A exhibited notably greater improvement after 8 weeks of training compared to those in Stratum B. Furthermore, both Stratums displayed significantly greater improvement following 8 weeks of training compared to sham training. In Stratum B cases, a significantly higher level of improvement was noted with the 4-week training in comparison to the sham training. A significant increase in NEADL index and 6MWT score was observed during the 24-week follow-up period. Conclusion For individuals with moderately weak inspiratory muscle strength, a 4-week exercise program proves sufficient in enhancing inspiratory muscle strength, walking capacity, and daily life activities. However, individuals with severely weak inspiratory muscle strength benefit more from an 8-week treatment.

Prolonged sitafloxacin and doxycycline combination regimen for treating infections by highly resistant Mycoplasma genitalium.

Mycoplasma genitalium, which causes sexually transmitted diseases, is increasingly resistant to key antibiotics such as macrolides and quinolones, posing a challenge for treatment. To assess the effectiveness of prolonged sitafloxacin and doxycycline combination therapy as a new alternative treatment strategy for highly drug-resistant M. genitalium strains. A prospective cohort study was conducted at the National Center for Global Health and Medicine, Tokyo, Japan, from 1 January 2020 to 31 October 2022. Patients with M. genitalium urogenital or rectal infections and those who did not receive the initial sitafloxacin monotherapy were included. Patients were administered sitafloxacin and doxycycline for 21 days as salvage therapy. M. genitalium isolates were tested for parC, gyrA and 23S rRNA resistance-associated mutations. Twenty-seven patients received the combination therapy. All M. genitalium strains available for resistance analysis had parC (24/24) and macrolide resistance-associated (25/25) mutations, and 68% (17/25) had gyrA mutations. The overall cure rate was 77.8%. For strains with concurrent parC and gyrA mutations, the cure rate was 68.8% (P = 0.053) compared with that for monotherapy (37.5%). Prolonged combination therapy is highly effective against M. genitalium strains with concurrent parC and gyrA mutations. Future research should focus on establishing the optimal treatment duration and monitoring the risk of resistance.

A call for academic pragmatic clinical trials to address open questions in migraine prevention.

The migraine treatment landscape has seen significant advancements in recent years, including the introduction of novel preventive agents specifically targeting the disease. These new treatments offer improved efficacy and tolerability, potentially addressing the issue of poor treatment adherence commonly observed with conventional preventatives. In this context, pragmatic trials emerge as a critical tool for advancing migraine care, offering a real-world approach to evaluating open clinical questions at the same time as avoiding the biases of real-world observational evidence. By prioritizing external validity and patient-centered outcomes, pragmatic trials provide valuable insights into the advantages of new treatments in improving migraine care. Possible applications of pragmatic trials in migraine research include head-to-head comparisons, evaluation of combination therapies, assessment of treatment sequences and switch, testing the added value of patient-reported outcomes, investigation of long-term effectiveness and on optimal treatment duration, understanding the role of preventive treatments in altering the course of migraine and preventing progression, and cost-effectiveness analyses. Pragmatic trials allow for the assessment of interventions in diverse patient populations and healthcare settings, enhancing the generalizability of findings and informing evidence-based clinical practice. As such, pragmatic trials represent an excellent tool to bridge the gap between placebo-controlled trials and real-world practice and should receive consideration for funding, especially by public institutions such as universities, national health services, and charities.

P07 The use of JAK inhibitors in difficult-to-treat adult-onset Still’s disease

Abstract Introduction Adult-onset Still’s Disease (AOSD) is a rare systemic auto-inflammatory disorder characterised by fever, arthritis and rash. Some patients with AOSD exhibit resistance or intolerance to conventional treatments, necessitating alternative therapeutic strategies. This case explores the efficacy and safety of janus kinase (JAK) inhibitors in managing difficult-to-treat AOSD. The driving force behind Still’s disease lies in the excessive and inappropriate production of pro-inflammatory cytokines, notably interleukin-6 (IL-6) and interferon (IFN). Given the pivotal role of JAK inhibitors in mitigating these cytokine pathways, this study highlights their potential therapeutic impact in the management of difficult-to-treat AOSD. Case description A 32-year-old male presented in July 2021 with a three-week history of fevers, night sweats, rigors, and weight loss. A CT scan revealed widespread lymphadenopathy above and below the diaphragm. Blood cultures were negative and, despite antibiotics, the patient continued to experience intermittent fevers. Anemia was asymptomatic, and the patient was transfused with two units of blood. Chronic B infection led to the initiation of entecavir. The patient also experienced palpitations and tachycardia, with an echo revealing a small pericardial effusion, hypertrophied and hyperdynamic left ventricle (LV) with an ejection fraction of 70-75%. A lymph node biopsy was inconclusive, prompting a second biopsy. In September 2021, hyponatremia due to SIADH developed. The patient had ongoing symptoms, including weight loss, and a bone marrow biopsy showed reactive features. CT and PET scans revealed generalised lymphadenopathy. Rheumatology consultation in November 2021 indicated intermittent fever, weight loss, joint pain, and elevated inflammatory markers. The patient had dermatographic lymphadenopathy, and a negative lymph node biopsy lowered the probability of HLH. Methotrexate was initiated, later switched to azathioprine and prednisolone due to ongoing symptoms. In June 2022, the patient started tocilizumab, which resolved joint pain but caused ongoing dermatitis. Tocilizumab was discontinued in January 2023 due to inefficacy, and anakinra was initiated. Prednisolone was gradually tapered off. The patient experienced shortness of breath, and echo revealed pulmonary hypertension. Tocilizumab was discontinued due to injection site reactions and increased hepatitis B virus titers. In March 2023, the decision was made to start the JAK inhibitor tofacitinib. By May 2023, ferritin levels were 1196, and the patient was successfully coming off prednisolone with well-controlled symptoms. Discussion This case underscores the efficacy of JAK inhibitors as a successful therapeutic intervention in challenging cases of AOSD. The 32-year-old male presented with severe symptoms including fevers, night sweats, weight loss, and widespread lymphadenopathy. Initial treatments with antibiotics, methotrexate, azathioprine, prednisolone, and tocilizumab were either ineffective or led to adverse reactions. Despite these setbacks, the patient showed a remarkable clinical response to the JAK inhibitor tofacitinib, initiated in March 2023. The swift and sustained improvement in symptoms, along with a favourable safety profile, suggests that JAK inhibitors can be a promising treatment for refractory AOSD. The ability to taper off steroids while maintaining symptom control is particularly noteworthy, as long-term steroid use is associated with significant side effects. The success of JAK inhibitors in this case is likely attributed to their mechanism of action, which strategically blocks pro-inflammatory cytokine pathways, particularly IL-6 and IFN. This targeted approach addresses the underlying pathophysiology of AOSD, leading to better disease management. However, this case also highlights the importance of monitoring for potential side effects, such as increased hepatitis B virus titres observed in this patient. This necessitated adjustments in therapy and careful monitoring of liver function. The encouraging outcomes in this case prompt the need for further prospective studies to validate these findings. Future research should focus on elucidating the optimal dosing and duration of JAK inhibitor therapy in patients with refractory AOSD. Additionally, long-term follow-up studies are essential to fully understand the safety profile of these agents. Key learning points • Refractory AOSD treatment: JAK inhibitors, such as tofacitinib, can be effective for patients with refractory AOSD who do not respond to conventional therapies. • Steroid sparing: JAK inhibitors may allow for the tapering off of steroids, reducing the risk of long-term steroid-related side effects. • Cytokine pathway targeting: The success of JAK inhibitors highlights the importance of targeting specific pro-inflammatory cytokine pathways, particularly IL-6 and IFN, in managing AOSD. • Monitoring side effects: Continuous monitoring for potential side effects, including increased the risk of thromboembolic events is crucial when using JAK inhibitors. • Need for further research: Prospective studies are needed to validate the efficacy and safety of JAK inhibitors in AOSD and to determine optimal dosing and treatment duration.

The contribution of SLC7A11-mediated ferroptosis to cardiac injury in iron overload cardiomyopathy: an in vitro study

Abstract Background Recent studies have indicated that iron overload can induce myocardial ferroptosis in iron overload cardiomyopathy (IOC), but the specific mechanisms, including the role of SLC7A11, remain unclear. Purpose By delving into the role of SLC7A11-mediated ferroptosis in IOC, this research endeavors to provide novel insights and therapeutic strategies for understanding and treating IOC. Methods To induce an in vitro model of IOC, wild-type rat cardiomyocytes (H9C2) were cultured in a ferric citrate (FAC) medium. Cardiomyocytes were exposed to various concentrations of iron overload (ranging from 0 mM to 2 mM) for durations of 4, 8, 12, and 24 hours. Cell viability at different FAC concentrations was assessed by the cell counting kit-8 (CCK8) assay and the level of the ferroptosis indicator malondialdehyde (MDA) was measured to determine the optimal concentration and duration of FAC treatment which was required to establish the IOC cell model. Next, ferroptosis indicators, including MDA, prostaglandin peroxide synthase 2 (PTGS2), and glutathione peroxidase 4 (GPX4), and the pivotal factor, SLC7A11 of IOC cardiomyocytes were evaluated. The protein and mRNA levels of SLC7A11 were assessed by molecular biology techniques. Additionally, the mitochondrial morphology of the IOC cardiomyocytes was meticulously examined by transmission electron microscopy (TEM). Flow cytometry was employed for detecting reactive oxygen species (ROS) levels. Furthermore, we elucidated the underlying mechanism of myocardial injury in IOC by overexpressing SLC7A11 and subsequently detecting changes in ferroptosis markers. Results CCK-8 results showed that the viability of cardiomyocytes exhibited dose-dependently with increasing FAC concentration (R2=0.5483, p<0.0001). Furthermore, the viability of cardiomyocytes remained relatively stable, with survival rates of approximately 50% and not decreasing below 50%. Additionally, the MDA content in IOC cardiomyocytes increased dose-dependently with the elevation of FAC concentration (R2=0.75, p<0.05), with a significant increase observed at 0.75mM. Expression levels of ferroptosis marker genes, GPX4 and PTGS2, both at the mRNA and protein levels, are indicative of diminished antioxidant capacity. Meanwhile, the level of myocardial MDA and ROS were markedly elevated, indicating underscoring increased oxidative stress within the IOC cardiomyocytes. Moreover, there was a downregulation in the expression of SLC7A11 mRNA and protein in IOC cardiomyocytes, suggesting a potential compensatory mechanism to counteract oxidative damage. TEM further elucidated cardiac mitochondrial injuries in IOC rats, including focal vacuolization, swelling, crest disruption, and even disappearance. Overexpression of SLC7A11 resulted in a significant augmentation of GPX4 and a reduction of PTGS2mRNA and protein expression levels. Conclusions Ferroptosis, mediated by SLC7A11, may represent a pivotal mechanism underlying myocardial injury in IOC.

Multi-year recurrent pericarditis disease duration in Italian patients: clinical outcomes after cessation of long-term IL-1 pathway inhibition provide insights for chronic management

Abstract Background Recurrent pericarditis (RP) is a chronic disease mediated by IL-1 often lasting for years, and specific tools to guide treatment duration with IL-1 pathway inhibition at the individual patient (pt) level are limited. The Phase 3 trial RHAPSODY and 2-year long-term extension (LTE) demonstrated that rilonacept reduced risk of recurrence over long-term treatment (1,2). At the conclusion of the LTE, after a median of 28 months of rilonacept treatment (non-US pts), Italian pts returned to standard management because rilonacept was not commercially available. Clinical outcomes after rilonacept cessation and washout were followed to inform disease persistence and time to recurrence. Purpose Multicentric analysis of RP event rates in Italian pts after stopping long-term rilonacept. Methods Clinical records from Italian RHAPSODY pts were examined for the 18-month period post-LTE (To). Primary outcome: pericarditis recurrence (defined by tertiary-center experts as pericarditis pain plus c-reactive protein [CRP] elevation). Secondary outcomes: time to recurrence and proportion of pts requiring re-initiation of IL-1 pathway inhibition. Safety outcomes: serious adverse events (SAEs). Results 17 Italian pts were observed (Table 1). At To, median [Q1-Q3] disease duration (time from index episode) was 48 [41-56] months, during which pts had received a median 28 [27-30] months of continuous rilonacept treatment (all were in Clinical Response, i.e., no pain, normalized CRP, and on rilonacept monotherapy). After rilonacept cessation at To, no pts received prophylactic treatment. 82.4% (14/17) of pts experienced confirmed pericarditis recurrences, with time to recurrence 8 [6-9] weeks. Half of these pts (n=7) were given oral medications (NSAIDS, colchicine [n=3] and/or steroids [n=4], of whom 1 steroid-treated pt failed and resumed IL-1 pathway inhibition). The other half (n=7) resumed IL-1 pathway inhibition directly upon recurrence. The remaining 17.6% (3/17) of pts had no pericarditis recurrences after To and remained off treatment during the observation period. No pts experienced SAEs. Neither recurrence frequency nor time to recurrence was significantly related to baseline disease characteristics or demographics. Conclusions This exploratory analysis shows that in pts with RP of even 4-years’ duration (including a median 28-months’ rilonacept treatment), the 80% recurrence rate after treatment cessation was indicative of severe persistent underlying disease. Time to pericarditis recurrence after rilonacept cessation (median 8 weeks) was consistent with the predicted gradual pharmacokinetic washout and previously-reported 8.6-week time to flare in RHAPSODY (1). Pericarditis recurrences in these pts with long disease duration and systemic inflammation were severe enough to necessitate re-initiation of advanced therapy. Further studies could quantify optimal treatment duration for pts achieving prolonged remission on IL-1 pathway inhibition.

Magnesium and Potassium Supplementation for Systolic Blood Pressure Reduction in the General Normotensive Population: A Systematic Review and Subgroup Meta-Analysis for Optimal Dosage and Treatment Length

Background/Objectives: Studies have shown that consistent reductions of 2 mm Hg in systolic blood pressure (SBP) for the general normotensive population can result in significant decreases in mortality from heart disease and stroke. The purpose of this meta-analysis was to determine the optimal dose and duration of treatment for magnesium and potassium supplementation, having previously discovered that both reduce SBP by −2.79 and −2.10 mm Hg, respectively. Methods: Placebo-controlled, randomized clinical trials examining the effects of magnesium and potassium supplementation on SBP were identified. Pairwise meta-analyses with subgroups for dosage and treatment duration were run. Results: Magnesium at dosages of ≤360 mg/day and durations greater than 3 months reduced SBP by −3.03 and −4.31 mm Hg, respectively. Potassium at dosages of ≤60 mmol/day and durations greater than 1 month reduced SBP by −2.34 and −2.80 mm Hg, respectively. Conclusions: Both supplements demonstrated greater reductions in SBP for the general population at lower dosages and longer treatment durations. Future studies are needed to validate these findings and provide tailored recommendations. These studies could investigate varying dosages over long-term follow-up to provide robust data on optimal dosages and treatment durations, as our findings were limited due to reliance on previously published trials.

Effects of propranolol on the biological behavior of human umbilical vein endothelial cells and the expression of SOX18, MMP-7, and VEGFA

To investigate the effects of propranolol on the proliferation, apoptosis, migration, and tube formation ability of human umbilical vein endothelial cells (HUVEC), as well as its impact on the expression of sex-determining region Y-box 18 (SOX18), matrix metalloproteinase-7 (MMP-7), and vascular endothelial growth factor A (VEGFA). HUVEC were treated with different concentrations of propranolol, and cell viability was assessed using the CCK-8 method to determine the optimal concentration and treatment duration. The experiment consisted of a control group and groups treated with different concentrations of propranolol (50, 100, 150 μmol/L). Apoptosis, migration, and tube formation of HUVEC were observed using flow cytometry, wound healing assays, and tube formation assays. Western blot and real-time quantitative PCR were used to detect the expression levels of SOX18, MMP-7, and VEGFA proteins and mRNA. Compared to the control group, the apoptosis rate in the propranolol treatment groups increased significantly (P<0.05), and it rose significantly with increasing drug concentration (P<0.05). The wound healing rate decreased in the propranolol treatment groups, and both the number of tube formation nodes and total tube length were reduced (P<0.05). The expression levels of SOX18, MMP-7, and VEGFA proteins and mRNA were downregulated in the propranolol treatment groups (P<0.05). Propranolol can inhibit the proliferation, migration, and tube formation ability of HUVEC and promote cell apoptosis, resulting in decreased expression levels of SOX18, MMP-7, and VEGFA.

Update on Neoadjuvant and Adjuvant BRAF Inhibitors in Papillary Craniopharyngioma: A Systematic Review

Background/Objectives: The recent discovery of BRAF mutation in papillary craniopharyngiomas opened new avenues for targeted therapies to control tumour growth, decreasing the need for invasive treatments and relative complications. The aim of this systematic review was to summarize the recent scientific data dealing with the use of targeted therapies in papillary craniopharyngiomas, as adjuvant and neoadjuvant treatments. Methods: The PRISMA guidelines were followed with searches performed in Scopus, MEDLINE, and Embase, following a dedicated PICO approach. Results: We included 21 pertinent studies encompassing 53 patients: 26 patients received BRAF inhibitors (BRAFi) as adjuvant treatment, while 25 received them as neoadjuvant treatment. In the adjuvant setting, BRAFi were used to treat recurrent tumours after surgery or adjuvant radiation therapy. The most common regimen combined dabrafenib (BRAFi) with trametinib (MEK1 and 2 inhibitor) in 81% of cases. The mean treatment length was 8.8 months (range 1.6 to 28 months) and 32% were continuing BRAFi. A reduction of tumour volume variable from 24% to 100% was observed at cerebral MRI during treatment and volumetric reduction ≥80% was described in 64% of cases. Once the treatment was stopped, adjuvant treatments were performed to stabilize patients in remission in 11 cases (65%) or when a progression was detected in three cases (12%). In four cases no further therapies were administered (16%). Mean follow-up after the end of targeted therapy was 17.1 months. As neoadjuvant regimen, 36% of patients were treated with dabrafenib and trametinib with a near complete radiological response in all the cases with a mean treatment of 5.7 months. The neoadjuvant use of verumafenib (BRAFi) and cometinib (MEK1 inhibitor) induced a near complete response in 15 patients (94%), with a median volumetric reduction between 85% and 91%. Ten patients did not receive further treatments. Side effects varied among studies. The optimal timing, sequencing, and duration of treatment of these new therapies should be established. Moreover, questions remain about the choice of specific BRAF/MEK inhibitors, the optimal protocol of treatment, and the strategies for managing adverse events. Conclusions: Treatment is shifting to a wider multidisciplinary management, where a key role is played by targeted therapies, to improve outcomes and quality of life for patients with BRAF-mutated craniopharyngiomas. Future, larger comparative trials will optimize their protocol of use and integration into multimodal strategies of treatment.

GLP-1 Receptor Agonists and the Path to Sustainable Obesity Care

This Viewpoint discusses the optimal treatment duration of glucagon-like peptide-1 receptor agonists in people with obesity and the benefits of off-ramping, the tapering of these antiobesity medications following an initial treatment period.

Comparison of Short vs. Extended Antibiotic Durations for Patients in the Neonatal Intensive Care Unit with Late Onset, Culture-negative Sepsis

Abstract Background Culture-proven late-onset sepsis in neonates and preterm infants, defined as symptom onset after 3-7 days of life, is a common cause of morbidity and mortality. Some patients are treated with antibiotics for sepsis despite lack of positive cultures after 48 hours of incubation, potentially due to the non-traditional signs of sepsis. Controversy remains over optimal treatment durations of culture-negative sepsis with durations reported as 2 to 7 days, and rarely longer than 7 days. The primary outcome of this study is to compare lack of symptom resolution at 7 days in patients with negative cultures treated with antibiotics for either ≤72 hours or &amp;gt;72 hours. Methods This was a single-center, retrospective, cohort study with Institutional Review Board approval at a 60 bed, level 4, surgical referral neonatal intensive care unit from January 1, 2020, to December 31, 2021. Patients were included for screening if they were ≥7 days of age, ≤ 44 weeks postmenstrual age, and received more than 1 day of antibiotics for possible late-onset, culture-negative sepsis. Patients were then excluded if they had positive culture results from any site, diagnosis of pneumonia, were being treated for suspicion of necrotizing enterocolitis, received antibiotics prior to obtaining cultures, or had continued treatment of prior infection. Patients were divided into two groups based on antibiotic duration: ≤72 hours or &amp;gt;72 hours. Presenting symptoms and symptom resolution at 72 hours and 7 days were assessed. Chi-squared or Fisher’s exact tests were used for categorical comparisons. Results Of the 909 patients screened, 68 were included: 42 in the ≤72 hours group and 26 in the &amp;gt;72 hours group. The most prevalent symptoms prompting antibiotic initiation were elevated CRP (64.7%) and bradycardia/oxygen desaturations (78%), with elevated CRP being the initiating symptom more frequently in the &amp;gt;72-hour group (92% vs 48%, p&amp;lt;0.001). If patients had 2 or more symptoms, they were more likely to receive &amp;gt;72 hours of antibiotics (85% vs 62%, p=0.034). At 7 days, 28 (41%) patients had complete symptom resolution. Antibiotic duration ≤72 hours was not associated with symptom resolution at 7 days (50% symptom resolution in the ≤72-hour group vs 27% in the &amp;gt; 72-hour group, p=0.06). Lack of symptom resolution at 72 hours of antibiotics was associated with lack of resolution at 7 days (p&amp;lt;0.001). Among patients without symptom resolution at 7 days, 65% of patients had a persistently elevated CRP and 68% of patients continued to have bradycardia/oxygen desaturations. Conclusion In neonates and preterm infants with negative cultures but possible signs of sepsis, antibiotic duration does not impact 7-day symptom resolution. Results indicate that if the initiating symptom is not resolved at 72 hours despite negative cultures, it is unlikely to be resolved with additional days of antibiotics. This is likely due to the multifactorial potentially non-infectious etiology of initiating symptoms in these patients. It is appropriate to discontinue antibiotics if cultures are negative after 48 hours of incubation in this population.

Short- versus standard-course antibiotic therapy for urinary tract infection in children: a systematic review and meta-analysis.

Urinary tract infections are prevalent among children and are responsible for a significant healthcare burden. Antibiotic therapy is the cornerstone of treatment, but the optimal treatment duration remains elusive. This systematic review and meta-analysis aimed to explore the optimal duration of antibiotic therapy for urinary tract infection (UTI) in pediatric patients. A comprehensive search was performed, including MEDLINE, Embase, and Cochrane Library databases. We included only randomized controlled trials (RCTs) comparing short-course (2 to 5days) and standard-course (≥ 7days) antibiotic treatment in patients < 18years of age. We performed this systematic review and meta-analysis following Cochrane Collaboration recommendations using a random-effects model. Effect estimate was calculated using the risk ratio (RR) with 95% confidence interval (95% CI) for dichotomous and mean difference (MD) with 95% CI for continuous endpoints. Significance was regarded at p-value < 0.05. Statistical analysis was performed using Review Manager 5.4.1. Data from 12 RCTs, encompassing 1442 children, were included. Follow-up ranged from 1 to 12months. The mean age was 5.9years, with approximately 87% female patients. E. coli was the most common pathogen isolated from urine cultures. There was a significant difference in cure rates (RR 0.97; 95% CI 0.95-0.99; p = 0.01) between the groups when only studies that included febrile UTI were analyzed together, favoring 7days or more of treatment, but with high heterogeneity. Otherwise, there was no significant difference in cure rates (RR 0.99; 95% CI 0.91-1.08; p = 0.80) in children with afebrile UTI or recurrence of UTI at any time in children with afebrile (RR 0.98; 95% CI 0.84-1.15; p = 0.80) or febrile UTI (RR 0.52; 95% CI 0.10-2.83; p = 0.45). Also, there was no significant difference in failure rates in children with urinary tract abnormalities and afebrile UTI (RR 0.79; 95% CI 0.47-1.32; p = 0.36), between the short- and the standard-course treatment groups. This analysis was limited by the moderate heterogeneity and the small subgroup of children with urinary tract abnormalities, which could have underpowered our results. The primary outcome of this analysis suggests that a short course of antibiotic therapy is feasible in children with afebrile UTI, but more studies are warranted to safely establish an optimal treatment duration for children with febrile UTI. The study protocol was registered in the PROSPERO platform under the number CRD42023489094.

Long-term monitoring and treatment of venous thromboembolic disease: recommendations of the Thromboembolic Disease Group of the Spanish Society of Internal Medicine 2024

Venous thromboembolim (VTE) is a highly prevalent condition that requires long-term monitoring and treatment. This monitoring includes: 1) completing the etiological study and determining the risk of VTE recurrence; 2) establishing the optimal duration of anticoagulant treatment, as well as the type of therapy and its dosage; 3) estimating the risk of bleeding, and 4) identifying the occurrence of chronic complications. This consensus document, prepared by the VTE Group of the Spanish Society of Internal Medicine (SEMI), aims to update and establish consensus recommendations on these aspects. The document focuses on four aspects of management: the first includes risk factors for VTE recurrence after an unprovoked VTE episode and describes the predictive scores of VTE recurrence; the second focuses on risk factors for bleeding; the third provides recommendations for long-term follow-up in VTE, addressing specific considerations for screening chronic thromboembolic pulmonary hypertension and post-thrombotic syndrome of the lower limbs; and the fourth provides guidance on the optimal duration of extended anticoagulant treatment, as well as the type of therapy and its dosage. For each area, an exhaustive literature review was conducted, analyzing the updated VTE clinical guidelines and recent studies. This document is intended to be a guide in the long-term management of VTE based on the most current knowledge.

The optimal antibiotic treatment duration for community-acquired pneumonia in adults diagnosed in general practice in Denmark (CAP-D): an open-label, pragmatic, randomised controlled trial

BackgroundUse of antibiotics is the main driver of antimicrobial resistance which is considered one of the biggest threats to human health. In Denmark, most antibiotics are prescribed in general practice. Acute lower respiratory tract infections, including community-acquired pneumonia (CAP), are among the most frequent indications for antibiotic prescribing. Phenoxymethylpenicillin is established as first-line treatment in general practice in Denmark. However, the treatment duration with phenoxymethylpenicillin is mostly based on traditions. Both 5 and 7 days of treatment is recommended in Danish guidelines, and when asking the general practitioners about what treatment duration, they prescribe the variation is even bigger. Several hospital-based studies have proven short course (≤ 6 days) antibiotic treatment non-inferior to long course (≥ 7 days) treatment of CAP. No evidence exists on the optimal treatment duration for CAP in non-hospitalised patients.This randomised controlled trial aim to investigate the optimal treatment duration with phenoxymethylpenicillin for CAP in adults diagnosed in general practice in Denmark.MethodsThis is an open-label, pragmatic, randomised controlled, five-arm DURATIONS trial. Participants will be recruited from at least 24 general practices in Denmark. Eligible participants are adults, with no pre-existing lung disease, presenting with symptoms of CAP, and in whom the general practitioner finds it relevant to treat with antibiotics. The study will compare treatment with phenoxymethylpenicillin 1.2 MIE q.i.d. in 3, 4, 5, 6, and 7 days.DiscussionThis study will provide evidence for the optimal antibiotic treatment duration of CAP in general practice and inform future guidelines on CAP in all countries using phenoxymethylpenicillin for the treatment of acute respiratory tract infections in adults. The results of this study might also be used to guide treatment recommendations in other countries using phenoxymethylpenicillin.Moreover, a (potential) reduction in antibiotic use might lower the development of antimicrobial resistance, increase patient treatment adherence, reduce risks of adverse events, and lower the economical expTrial registrationClinicalTrials.gov: NCT06295120. Registered 28 February 2024. The Scientific Ethics Committee for the North Denmark Region: N-20230039.

Optimized anti-tuberculosis duration for drug-susceptible pulmonary tuberculosis-diabetes mellitus comorbidities: study protocol for a multicenter randomized controlled trial

BackgroundThe coexistence of tuberculosis (TB) and type 2 diabetes mellitus (DM) presents unique challenges in treatment optimization and management, given the mutual exacerbation of disease processes.ObjectiveThis multicenter, open-label, randomized controlled trial aims to evaluate the efficacy and safety of two different treatment durations (6-month versus 9-month regimens) regimen for patients with drug-susceptible pulmonary tuberculosis (DS-PTB) and concurrent type 2 diabetes (DM).MethodsPatients with DS-PTB and type-2 DM from 22 hospitals in China are enrolled. They are randomized in a 1:1 ratio into either the 6-month regimen arm(2HRZE/4HR) or the 9-month regimen arm(2HRZE/7HR). At the end of the intensive phase (the 8th week), patients in both arms who with sputum positive smear will extent one more month of intensive treatment. The primary outcome is the proportion of unfavorable outcomes at 24 months after randomization. Secondary outcomes include treatment success rate at the end of treatment, proportion of recurrence at 24 months after randomization, time to recurrence after treatment completion, proportion of intensive phrase extension, occurrence of adverse events grade 3 or above during treatment.DiscussionThe study focuses on assessing the optimal treatment duration to maximize treatment success while minimizing recurrence and adverse events. The trial is expected to provide vital insights into the appropriate treatment duration for patients with TB-DM, aiming to reduce recurrence rates and improve overall treatment outcomes in this vulnerable population.Trail registrationChictr.org.cn, ChiCTR2100044663. Registered on March 25, 2021.

Impact of plasma treatment of Au electrodes on response of EIS biosensors used in aquaculture pathogen detection

This study examines the effect of plasma treatment on gold electrodes used in construction of biosensors. Plasma treatment aims to improve the adhesion of bioreceptor layers, enhancing sensor performance. Gold substrates were exposed to plasma for different durations, and their reactivity was analyzed using electrochemical impedance spectroscopy (EIS), atomic force microscopy (AFM), and scanning electron microscopy (SEM). Results show that plasma treatment significantly enhances the hydrophilicity of gold surfaces, leading to better formation of bioreceptor layer. Optimal treatment duration was found to be around 60 s, beyond which improvements in impedance values diminished. Plasma-treated electrodes displayed superior bioreceptor adhesion without altering surface topography. In conclusion, plasma treatment improves biosensor performance by enhancing bioreceptor layer adhesion. Integrating this process into biosensor production can lead to more efficient and reliable pathogen detection in aquaculture, promoting healthier aquatic environments and sustainable food production.

Enhanced energy harvesting of fibrous composite membranes via plasma-piezopolymer interaction

Electroactive sites and crystallinity play a key role to improve the energy conversion performance of piezoelectric polymeric composites. However, these characteristics are attained through time-consuming thermal annealing (TA), which limits the practicality of flexible piezoelectric harvesters (f-PEHs). Here, a short-time plasma annealing (PA) technique was introduced to piezoelectric composite fibers (PCFs) for rapid crystallization and enhanced electroactive β-phase of polymer. The percentage of change in crystallinity of 10-minute PA treated PCF is 20 % compared to TA-treated PCF (annealing time = 2 h), which results in a higher voltage of 2.4 times and current of 3.8 times than the TA-based f-PEH. Finite element analysis confirmed the optimal PA treatment duration and superior performance of PA-treated PCFs. Further PA treated f-PEH was tested for vibration sensor by attaching it to a circulator pipe, confirming its high potential for accurately detecting variations in flow velocity (8–28 L/min). These results demonstrate that PA is an efficient technique for producing high-performance f-PEHs with an increased crystallinity (Xc =22.81 %) in a short time (10 minutes), offering a practical solution for consumer electronic devices and wireless sensors.

Omega-3 polyunsaturated fatty acids in depression: insights from recent clinical trials

Purpose of review This review examines evidence from recent clinical trials on the therapeutic potential of omega-3 polyunsaturated fatty acids (PUFAs) in major depressive disorder (MDD). We focus on the effects in MDD with comorbidities, younger populations, and high-inflammation presentations. Recent findings PubMed, Cochrane, and Embase databases were systematically searched for studies published between May 2022 and May 2024. The search was conducted on randomized controlled trials using omega-3 PUFAs with participants with a clinical diagnosis of depression. Higher doses of eicosapentaenoic acid (EPA) (&gt;1 g/day) improved measures of depression, particularly in MDD with elevated inflammation markers, comorbid cardiovascular diseases, late-life onset, and children and adolescent populations. Improvements in depressive symptoms were associated with increases in omega-3 PUFA-derived anti-inflammatory and proresolving lipid mediators. As adjuvant treatments, omega-3 PUFAs have potential benefits in mood, cognitive and metabolic functions, kynurenine and serotonin pathways, and alterations in corticolimbic functional connectivity. Summary While evidence suggests promise, particularly for high-dose EPA and in inflammatory MDD subtypes, more research is needed to establish optimal dosing regimens, treatment duration, and patient subgroups most likely to benefit. Future studies should focus on sex differences, long-term effects, and potential synergies with other treatments.

Antiseizure Medication Use and Outcomes After Suspected or Confirmed Acute Symptomatic Seizures

Antiseizure medications (ASMs) are frequently prescribed for acute symptomatic seizures and epileptiform abnormalities (EAs; eg, periodic or rhythmic patterns). There are limited data on factors associated with ASM use and their association with outcomes. To determine factors associated with ASM use in patients with confirmed or suspected acute symptomatic seizures undergoing continuous electroencephalography, and to explore the association of ASMs with outcomes. This multicenter cohort study was performed between July 1 and September 30, 2021, at 5 US centers of the Post Acute Symptomatic Seizure Investigation and Outcomes Network. After screening 1717 patients, the study included 1172 hospitalized adults without epilepsy who underwent continuous electroencephalography after witnessed or suspected acute symptomatic seizures. Data analysis was performed from November 14, 2023, to February 2, 2024. ASM treatment (inpatient ASM continuation ≥48 hours). Factors associated with (1) ASM treatment, (2) discharge ASM prescription, and (3) discharge and 3-month Glasgow Outcome Scale score of 4 or 5 were ascertained. A total of 1172 patients (median [IQR] age, 64 [52-75] years; 528 [45%] female) were included. Among them, 285 (24%) had clinical acute symptomatic seizures, 107 (9%) had electrographic seizures, and 364 (31%) had EAs; 532 (45%) received ASM treatment. Among 922 patients alive at discharge, 288 (31%) were prescribed ASMs. The respective frequencies of inpatient ASM treatment and discharge prescription were 82% (233 of 285) and 69% (169 of 246) for patients with clinical acute symptomatic seizures, 96% (103 of 107) and 95% (61 of 64) for electrographic seizures, and 64% (233 of 364) and 48% (128 of 267) for EAs. On multivariable analysis, acute and progressive brain injuries were independently associated with increased odds of inpatient ASM treatment (odds ratio [OR], 3.86 [95% CI, 2.06-7.32] and 8.37 [95% CI, 3.48-20.80], respectively) and discharge prescription (OR, 2.26 [95% CI, 1.04-4.98] and 10.10 [95% CI, 3.94-27.00], respectively). Admission to the neurology or neurosurgery service (OR, 2.56 [95% CI, 1.08-6.18]) or to the neurological intensive care unit (OR, 7.98 [95% CI, 3.49-19.00]) was associated with increased odds of treatment. Acute symptomatic seizures and EAs were significantly associated with increased odds of ASM treatment (OR, 14.30 [95% CI, 8.52-24.90] and 2.30 [95% CI, 1.47-3.61], respectively) and discharge prescription (OR, 12.60 [95% CI, 7.37-22.00] and 1.72 [95% CI, 1.00-2.97], respectively). ASM treatment was not associated with outcomes at discharge (OR, 0.96 [95% CI, 0.61-1.52]) or at 3 months after initial presentation (OR, 1.26 [95% CI, 0.78-2.04]). Among 623 patients alive and with complete data at 3 months after discharge, 30 (5%) had postdischarge seizures, 187 (30%) were receiving ASMs, and 202 (32%) had all-cause readmissions. This study suggests that etiology and electrographic findings are associated with ASM treatment for acute symptomatic seizures and EAs; ASM treatment was not associated with functional outcomes. Comparative effectiveness studies are indicated to identify which patients may benefit from ASMs and to determine the optimal treatment duration.