Short-course Treatment Research Articles

Perioperative adjuvant therapy with short course of dupilumab with ESS for recurrent CRSwNP.

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is associated with a high rate of disease recurrence following endoscopic sinus surgery (ESS). Type 2 disease is associated with a higher incidence of recurrence and is believed to impact disease resolution via interference with epithelial healing and pathogen immunity. We wished to verify if perioperative control of Type 2 inflammation with an anti-IL4/IL13 targeting monoclonal antibody and during the resolution period following surgery leads to better control of the disease long term. In this prospective, placebo-controlled, double-blinded trial. Thirty adult subjects with recurrent CRSwNP underwent ESS plus or minus 14 weeks of perioperative dupilumab, initiated 4 weeks (two injections) pre-ESS. Subjective and objective parameters of nasal patency, olfaction, quality of life (QoL), and adverse events were monitored up to 52 weeks post-ESS. Microbiological culture was performed to characterize pathogens colonization under both conditions. ESS safely improved subjective and objective measures of nasal patency, olfaction, and QoL in both groups. Olfaction was conserved longer in the dupilumab-treated group, with 33.3% of subjects presenting anosmia at 12 months after ESS in the dupilumab group compared to 50.0% with placebo. This was associated with persistent decreases in serum IgE, which were not seen with placebo treatment. No unusual safety signals were observed. Short-course adjuvant perioperative treatment with dupilumab is associated with improved long-term olfactory outcomes and persistent lowering of serum IgE.

Radiation therapy in the hypofractionation mode on the Halcyon elite linear accelerator: the first experience of St. Petersburg city clinical oncology dispensary

Stereotactic radiation therapy in the hypofractionation mode is a method in which high doses of ionizing radiation (more than 3 Gy per fraction) are delivered in a small number of fractions (from 2 to 5). Treatment and the process of preparation for it are carried out using special fixing devices, dosimetric planning techniques of high conformity, with control of the treatment position using x-ray imaging. which makes it possible to ensure the required irradiation accuracy. The advantages are a shorter course of treatment compared to standard fractionation, a high biologically effective dose, a reduced effect of tumor repopulation, greater efficiency under hypoxic conditions, and satisfactory results when irradiating radioresistant tumors. The article presents clinical cases of the use of hypofractionation modes on the Halcyon elite linear accelerator.

Comparative Efficacy of Current and Emerging Therapies for Cutaneous and Visceral Leishmaniasis: A Global Perspective

Leishmaniasis treatment has faced challenges with pentavalent antimonials, historically used but now showing resistance and high failure rates. The World Health Organization (WHO) recommended higher doses, but resistance in Nepal and misuse persist. Antimonials are no longer the preferred treatment for visceral leishmaniasis (VL) in the Indian subcontinent but are still used for cutaneous leishmaniasis (CL). Amphotericin B, especially liposomal amphotericin B (L-AmB), has become the preferred treatment for VL in the Indian subcontinent, with high efficacy and shorter treatment courses. Genetic insights into leishmaniasis reveal that parasite species and host immune responses are key factors in disease variation. Genetic analysis of atypical parasite isolates shows that genetic variations can lead to different disease patterns. Whole genome sequencing and proteomic analyses offer fresh insights into how parasite genes and proteins impact drug resistance, post-kala-azar dermal leishmaniasis (PKDL), and unusual disease presentations. Variations in hereditary unit copy numbers and single nucleotide polymorphisms contribute to genetic diversity and distinct tissue distribution, leading to distinct disease patterns. Genomic markers for drug resistance in Leishmania parasites include ATP-binding cassette (ABC) transporters, amino acid permease 3 (AAP3), and proteins like phosphoglycerate kinase (PGK) and mitogen-activated protein kinase (MAPK). These markers are associated with efflux of thiols and metals, antimony resistance, and protection against oxidative stress. Additionally, key proteins and enzymes in antioxidant defense mechanisms, such as iron superoxide dismutase-A (FeSOD-A), folate transporter 1 (FT1), and heat shock protein 83 (HSP83), play roles in drug resistance and parasite survival.

Duration of antimicrobial treatment for uncomplicated streptococcal bacteraemia: another example of shorter is better

ObjectivesDuration of treatment for uncomplicated streptococcal bacteraemia is unknown. The study aims to assess clinical outcomes of patients with uncomplicated streptococcal bacteraemia receiving a short course (5-10 days) of antimicrobial treatment compared to those receiving the traditional, longer duration (11-18 days). MethodsThis retrospective study was conducted at the Lausanne University Hospital, Switzerland and included episodes of uncomplicated streptococcal bacteraemia among adult patients from 2015 to 2023. Clinical failure was defined as mortality, recurrence of bacteraemia by the same streptococcal species and development in bone and joint infection within 120 days. ResultsDuring the study period, 336 episodes of uncomplicated streptococcal bacteraemia were included. The median duration of antimicrobial treatment was 10 days (interquartile range: 7-14); 184 (55%) and 152 (45%) episodes received a short (5-10 days) and long (11-18 days) duration of antimicrobial treatment, respectively. Forty-three (13%) episodes had clinical failure; 120-day mortality was 11% (36 episodes); recurrence of bacteraemia by the same streptococcal species was observed in 8 episodes (2%). No difference in clinical failure was observed between episodes receiving short and long courses of antimicrobial treatment (10% versus 16%; P 0.143). The Cox multivariable regression model found that a Charlson comorbidity index >4 (aHR 4.87, 95% CI 3.08-7.71), and septic shock (1.67, 1.04-2.67) were associated with clinical failure; a short course of antimicrobial treatment was not associated with clinical failure (0.90, 0.57-1.12). ConclusionsThis study has shown that a short duration of antimicrobial treatment for cases of streptococcal bacteraemia is effective and safe.

Practical Recommendations from the Gulf Region on the Therapeutic Use of Cladribine Tablets for the Management of Relapsing Multiple Sclerosis: Impact of the Latest Real-World Evidence on Clinical Practice.

Cladribine tablets (CladT), like alemtuzumab, acts as an immune reconstitution therapy. However, CladT is administered orally (alemtuzumab is given by infusion) and without the potential for serious side effects that limit the therapeutic use of alemtuzumab in multiple sclerosis (MS). Treatment with CladT, given initially as short courses of treatment 1year apart, provides years of freedom from MS disease activity in responders to treatment. The appearance of mild or moderate MS disease activity after the initial 2years of treatment may prompt careful follow-up or a further course of CladT, depending on the nature of the activity and individual circumstances. The appearance of severe MS disease activity requires a switch to an alternative high-efficacy disease-modifying treatment (DMT). The accumulating data from CladT-treated people with MS in real-world studies, including those with follow-up durations extending for years beyond the initial treatment, have demonstrated long-term freedom from MS disease activity in a good proportion of patients. This clinical experience has also confirmed that treatment with CladT is generally safe and well tolerated. The best time to prescribe a high-efficacy DMT is the subject of debate, with evidence that earlier versus later use of such agents may provide more effective long-term protection from disability progression. High-efficacy DMTs have traditionally been reserved for use in people with MS and high disease activity on presentation or breakthrough disease on one or more DMTs, as per the current product labels. The latest evidence from real-world studies suggests that CladT is effective and safe in DMT-naïve patients, including those with shorter disease duration.

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.

Significant drop in serum C-reactive protein in patients with solid neoplasia and bacterial infection is associated with a better prognosis and identifies candidates for short-course antibiotic therapy

IntroductionThe greater predisposition to infections, as well as the possibility of a worse response to treatment, can lead to the excessive use of antimicrobials among cancer patients. C-reactive protein (CRP) has gained prominence as a tool for monitoring therapeutic responses and reducing the duration of antibiotic therapy; however, few studies have analyzed this protein in cancer patient populations. We hypothesize that cancer patients with a good response to antibiotic therapy show a faster decline in serum CRP levels, which would allow us to identify candidates for short-course treatments.ObjectiveTo evaluate the behavior of serum CRP levels among adult cancer patients using antibiotic therapy, and its association with the duration of this treatment, therapeutic response, and clinical recurrence.MethodsThis work consisted of a retrospective study with cancer patients admitted to a university hospital between September 2018 and December 2019. Adults (age ≥ 18 years) who underwent at least one course of antibiotic therapy were included. CRP behavior over the first 7 days of treatment was classified as: i) good response: when the CRP value on the fifth day of therapy reached 50% or less of the peak value detected in the first 48 h of treatment, and ii) poor response: Maintenance, within the same interval, of a CRP value > 50% of the peak value in the first 48 h. The duration of antibiotic therapy was categorized as up to seven full days or more. Outcomes were assessed by events that occurred during the 30 days of hospitalization or until hospital discharge. Primary outcome: Clinical recurrence of the index infection. Secondary outcomes: i) Death from any cause; ii) microbiological recurrence; iii) therapeutic response; iv) colitis associated with Clostridioides difficile; and v) isolation of multi-resistant bacteria, whether in clinical or surveillance samples.ResultsThe final analysis consisted of 212 patients, with a median age (IQ) of 59.2 (48 – 67) years old and a predominance of females (65%), who were hypertensive (35%), smokers (21%), and diabetics (17.8%). There was no difference in clinical recurrence between the two groups (8.1% vs. 12.2%; p = 0.364), with a lower 30-day mortality in the good CRP response group (32.2% vs. 14.5%; p = 0.002). Despite the tendency towards a lower occurrence of other secondary outcomes in the good response group, these differences were not statistically significant. In the poor CRP response group, outcomes like clinical recurrence, mortality, and therapeutic response were significantly worse, regardless of the duration of antibiotic treatment.ConclusionIn this study, cancer patients with a good CRP response during antibiotic therapy presented lower mortality and a higher proportion of satisfactory therapeutic responses. CRP can be a useful tool when combined with other clinical information in optimizing the duration of antimicrobial treatment in a hospitalized cancer population.

Exploring the effects of short-course antibiotics on children’s gut microbiota by using 16S rRNA gene sequencing: a case-control study

BackgroundWith the widespread use of antibiotics, more attention has been paid to their side effects. We paid extra attention to the impact of antibiotics on children’s bodies. Therefore, we analyzed the characteristic changes in the gut microbiota of children after antibiotic treatment to explore the pathogenesis of antibiotic-associated diseases in more depth and to provide a basis for diagnosis and treatment.MethodsWe recruited 28 children with bronchopneumonia in the western district of Zhuhai, China, and divided them into three treatment groups based on antibiotic type. We took stool samples from children before and 3–5 days after antibiotic treatment. 16S rRNA gene sequencing was used to analyze the effects of antibiotic therapy on the gut microbiota of children. Continuous nonparametric data are represented as median values and analyzed using the Wilcoxon rank-sum test.ResultsWhile alpha diversity analysis found no significant changes in the mean abundance of the gut microbiota of children after a short course of antibiotic treatment, beta diversity analysis demonstrated significant changes in the composition and diversity of the gut microbiota of children even after a short course of antibiotic therapy. We also found that meloxicillin sulbactam can inhibit the growth of Proteobacteria, Bacteroidetes, and Verrucomicrobia, ceftriaxone inhibits Verrucomicrobia and Bacteroides, and azithromycin inhibits Fusobacteria, Actinobacteria, Proteobacteria, and Verrucomicrobia. We further performed a comparative analysis at the genus level and found significantly different clusters in each group. Finally, we found that azithromycin had the greatest effect on the metabolic function of intestinal microbiota, followed by ceftriaxone, and no significant change in the metabolic process of intestinal microbiota after meloxicillin sulbactam treatment.ConclusionsAntibiotic treatment significantly affects the diversity of intestinal microbiota in children, even after a short course of antibiotic treatment. Different classes of antibiotics affect diverse microbiota primarily, leading to varying alterations in metabolic function. Meanwhile, we identified a series of intestinal microbiota that differed significantly after antibiotic treatment. These groups of microbiota could be used as biomarkers to provide an additional basis for diagnosing and treating antibiotic-associated diseases.

Subcutaneous Immunotherapy of Food Allergy.

While there are compelling arguments for developing subcutaneous allergen-specific immunotherapy for alleviation of food allergies, there is a limited number of studies in the public domain. The review seeks to present the approaches taken, to explain the paucity of studies, and to identify new roads for development. A literature search revealed clinical trials of immunotherapy of food allergies to fish and peanut, but studies had limited patient numbers, short treatment courses and follow-up periods. Indications, but no clearcut effects, were seen with both classical allergen extracts and hypo-allergenic preparations. A special case is the influence on cross-reactive food allergies, when subcutaneously administered birch-pollen extracts are used for treatment of birch pollen hayfever and/or asthma. Again indications, but no convincing efficacy has been registered. Newer developments include recombinant hypoallergens and DNA-technologies. Subcutaneous immunotherapy for food allergies has not matured to provide clinically relevant treatment opportunities.

Effectiveness of short treatment duration for carbapenemase-producing Enterobacterales in bloodstream-infections: A retrospective cohort study

ObjectiveWe analyse the effectiveness of short courses of adequate treatment in patients with episodes of carbapenemase-producing Enterobacterales bloodstream-infections (CPE-BSI). MethodsPatients with first monomicrobial CPE-BSI episodes who received ≥72 h of appropriate treatment from 2014–2022 were selected. Detection of CPE was established on the basis of phenotypic antibiogram and confirmation by PCR and/or immunochromatographic methods. Patients were classified in short treatment group (STG) those who received 3–10 days of appropriate treatment, and long treatment (LTG) those receiving >10 days. Unfavourable outcome consisted in a composite of global 30-day mortality and/or persistent bacteremia and/or recurrent bacteremia. Inverse probability of treatment weighting (IPTW) analysis was performed to compare the outcome between the two study groups. ResultsWe included 105 CPE-BSI episodes: 99 were caused by OXA-48-like, 4 VIM and 2 KPC carbapenemases. Thirty-nine patients (37.1%) were included in the STG and 66 (62.9%) in LTG. The STG group presented frequent treatment with ceftazidime-avibactam (43.6% vs. 24.2%, P = 0.03) and lower in-hospital stay (21 days vs. 32 days, P = 0.02). Overall, 28 patients (26.7%) presented unfavourable outcome: IPTW analysis showed no differences in the outcome between STG to LTG groups (24.2% vs. 30.8%, weighted-risk difference 6.6%, P = 0.44). Patients with unfavourable outcome presented more frequently source other than urinary-biliary (46.4% vs. 23.4%, P = 0.02), received less frequently ceftazidime-avibactam (14.3% vs. 37.7%, P = 0.02) and presented frequently with absence of source control when indicated (28.6% vs. 13.0%, P = 0.06). ConclusionsShort treatment durations for CPE-BSI episodes may be effective, as long as they are appropriate and source control is performed.

Dose tracking assessment for magnetic resonance guided adaptive radiotherapy of rectal cancers

BackgroundMagnetic resonance-guided adaptive radiotherapy (MRgART) at MR-Linac allows for plan optimisation on the MR-based synthetic CT (sCT) images, adjusting the target and organs at risk according to the patient’s daily anatomy. Conversely, conventional linac image-guided radiotherapy (IGRT) involves rigid realignment of regions of interest to the daily anatomy, followed by the delivery of the reference computed tomography (CT) plan. This study aims to evaluate the effectiveness of MRgART versus IGRT for rectal cancer patients undergoing short-course radiotherapy, while also assessing the dose accumulation process to support the findings and determine its usefulness in enhancing treatment accuracy.MethodsNineteen rectal cancer patients treated with a 1.5 Tesla MR-Linac with a prescription dose of 25 Gy (5 Gy x 5) and undergoing daily adapted radiotherapy by plan optimization based on online MR-based sCT images, were included in this retrospective study. For each adapted plan (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:{\ ext{T}\ ext{P}}_{\ ext{a}\ ext{d}\ ext{a}\ ext{p}}$$\\end{document}), a second plan (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:{\ ext{T}\ ext{P}}_{\ ext{I}\ ext{G}\ ext{R}\ ext{T}}$$\\end{document}) was generated by recalculating the reference CT plan on the daily MR-based sCT images after rigid registration with the reference CT images to simulate the IGRT workflow. Dosimetry of \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:{\ ext{T}\ ext{P}}_{\ ext{a}\ ext{d}\ ext{a}\ ext{p}}$$\\end{document} and\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:\\:{\ ext{T}\ ext{P}}_{\ ext{I}\ ext{G}\ ext{R}\ ext{T}}$$\\end{document}was compared for each fraction. Cumulative doses on the first and last fractions were evaluated for both workflows. The dosimetry per single fraction and the cumulative doses were compared using dose-volume histogram parameters.ResultsNinety-five fractions delivered with MRgART were compared to corresponding simulated IGRT fractions. All MRgART fractions fulfilled the target clinical requirements. IGRT treatments did not meet the expected target coverage for 63 out of 94 fractions (67.0%), with 13 fractions showing a V95 median point percentage decrease of 2.78% (range, 1.65-4.16%), and 55 fractions exceeding the V107% threshold with a median value of 15.4 cc (range, 6.0-43.8 cc). For the bladder, the median \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:{\ ext{D}}_{15\ ext{c}\ ext{c}}$$\\end{document} values were 18.18 Gy for the adaptive fractions and 19.60 Gy for the IGRT fractions. Similarly the median \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:{\ ext{D}}_{5\ ext{c}\ ext{c}}$$\\end{document} values for the small bowel were 23.40 Gy and 25.69 Gy, respectively. No statistically significant differences were observed in the doses accumulated on the first or last fraction for the adaptive workflow, with results consistent with the single adaptive fractions. In contrast, accumulated doses in the IGRT workflow showed significant variations mitigating the high dose constraint, nevertheless, more than half of the patients still did not meet clinical requirements.ConclusionsMRgART for short-course rectal cancer treatments ensures that the dose delivered matches each fraction of the planned dose and the results are confirmed by the dose accumulation process, which therefore seems redundant. In contrast, IGRT may lead to target dose discrepancies and non-compliance with organs at risk constraints and dose accumulation can still highlight notable dosimetric differences.

Financial Improvements From Short Course Adjuvant Vaginal Cuff Brachytherapy in Early Endometrial Cancer Compared With Standard of Care, “SAVE” Trial

Early-stage endometrial cancer is often treated with hysterectomy followed by adjuvant vaginal cuff brachytherapy (VCB). Financial toxicity from cancer treatment can impact treatment completion. The Short Course Adjuvant Vaginal Cuff Brachytherapy in Early Endometrial Cancer Compared to Standard of Care trial is a multicenter, prospective randomized trial of standard of care (SoC) VCB doses delivered in 3 to 5 fractions per the physician's discretion compared with a 2-fraction course. We report on secondary cost endpoints, quantifying the financial impacts of shorter treatment courses on institutions and participating patients. Technical (TechCs), professional, and total charges (TotCs) were collected prospectively and are reported as raw and Medicare-adjusted charges per patient. Distance to the treatment center and the median income for each patient's zip code were estimated. The Mann-Whitney U statistic, t test, and X2 test were used to compare characteristics between the 2 groups. One hundred eight patients were analyzed. SoC VCB was delivered in 3, 4, and 5 fractions for 27 of 54 patients (50%), 11 of 54 (20%), and 16 of 54 (30%), respectively. The median total distance traveled per patient for SoC versus experimental arms was 213 versus 137 miles (p = .12), and the median cost of commute for patients was $36.3 versus $18.0 (p = .11). Compared with 2-fraction treatment, 5-fraction treatment resulted in longer travel distances (median, 462 vs 137 miles; p < .01) and increased travel costs (median, $59.3 vs $18.0; p ≤ .01). Unadjusted raw professional charges in USD per patient did not differ between SoC versus experimental arms ($9159 vs $7532; p = .19). TechCs were significantly higher in the SoC arm ($35,734 vs $24,696; p ≤ .01), as were TotCs ($44,892 vs $32,228; p < .01;). Medicare-adjusted TechCs and TotCs were higher for the SoC arm. Two-fraction VCB resulted in fewer treatments per patient, reduced cost of travel compared with longer courses, and an adjusted reduction in health care expenditures compared with SoC.

Short Treatment of 42 Days with Oral GS-441524 Results in Equal Efficacy as the Recommended 84-Day Treatment in Cats Suffering from Feline Infectious Peritonitis with Effusion-A Prospective Randomized Controlled Study.

In the past, feline infectious peritonitis (FIP) caused by feline coronavirus (FCoV) was considered fatal. Today, highly efficient drugs, such as GS-441524, can lead to complete remission. The currently recommended treatment duration in the veterinary literature is 84 days. This prospective randomized controlled treatment study aimed to evaluate whether a shorter treatment duration of 42 days with oral GS-441524 obtained from a licensed pharmacy is equally effective compared to the 84-day regimen. Forty cats with FIP with effusion were prospectively included and randomized to receive 15 mg/kg of GS-441524 orally every 24h (q24h), for either 42 or 84 days. Cats were followed for 168 days after treatment initiation. With the exception of two cats that died during the treatment, 38 cats (19 in short, 19 in long treatment group) recovered with rapid improvement of clinical and laboratory parameters as well as a remarkable reduction in viral loads in blood and effusion. Orally administered GS-441524 given as a short treatment was highly effective in curing FIP without causing serious adverse effects. All cats that completed the short treatment course successfully were still in complete remission on day 168. Therefore, a shorter treatment duration of 42 days GS-441524 15 mg/kg can be considered equally effective.

The Different Therapeutic Effects of Traditional Chinese Medicine Shensong Yangxin Capsule and Salubrinal in High-intensity Exercise-induced Heart Failure in Rats with Acute Myocardial Infarction.

Currently, endoplasmic reticulum stress is studied utilizing a dephosphorylation inhibitor (Sal). The traditional Chinese patent medicine and simple formulation Shensong Yangxin Capsule is a commonly used medication for the treatment of arrhythmia. However, the efficacy and underlying mechanism of the capsule in treating post-ischemic heart failure in myocardial tissue have not yet been investigated. The therapeutic effects and the underlying mechanism of the Shensong Yangxin Capsule (SSYX) and the dephosphorylation inhibitor Salubrinal (Sal) on heart failure (HF) induced by high-intensity exercise in rats with acute myocardial infarction (AMI) were investigated. Male infants of 8 weeks Spragge-Dawley (SD) rats were randomly assigned to one of four groups: sham surgery group, AMI+placebo group, AMI+Shensong Yangxin Capsule group (AMI+SSYX), and AMI+Sal administration group. Rats' myocardial infarction was induced by left coronary artery ligation. Rats were subjected to a 3-week high-intensity exercise program to simulate heart failure after 7 days of postoperative rest. After the fourth postoperative week, echocardiography was applied to determine the left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), and left ventricular systolic volume (LVESV) in each group. HE and TUNEL labeling were employed to examine the morphology of cardiac cells and measure the percentage of apoptosis in each group; Western blotting was applied to detect the cardiomyocyte apoptosis-related proteins p-JNK, p-P38, and NOX2, while ELISA was used to detect glutathione(GSH), malondialdehyde (MDA), and superoxide dismutase (SOD) in serum. Following a 4-week drug intervention:(1)LVFS and LVEF in the AMI+placebo group were statistically significantly reduced, while LVESV were significantly higher, compared to those in the sham surgery group (P<0.05); The AMI+SSYX group performed statistically significantly better than the AMI+placebo group(P<0.05). (2) The myocardial cells in the AMI+placebo group exhibited significant swelling and inflammatory cell infiltration; the myocardial cells in the AMI+SSYX group and AMI+Sal group displayed mild swelling and minimal inflammatory cell infiltration; the AMI+SSYX group's myocardial cell morphology was superior to that of the AMI+Sal group; (3) The apoptosis rate of the AMI+placebo group was around 95%, greater than that of the sham surgery group (2.55%). The apoptosis rate of the AMI+SSYX group is approximately 21%, while the apoptosis rate of the AMI+Sal group is about 43%. (4) In the AMI+placebo group, p-JNK, p-P38, and NOX2 protein expression dramatically increased compared to the sham surgery group. The expression of p-P38, NOX2, and p-JNK/t-JNK was considerably reduced in the AMI+Shensong group and AMI+Sal group, compared to the AMI+placebo group. (P<0.01)The AMI+SSYX group's result is superior to that of the AMI+Sal group. (5) Compared to the sham surgery group, the serum levels of SOD and GSH were significantly lower, and MDA was significantly higher in the AMI+placebo group. Compared to the AMI+placebo group, the serum levels of SOD and GSH were significantly higher, and MDA was significantly lower in the AMI+SSYX group and the AMI+Sal group. (P<0.05) Conclusion: In rats with acute myocardial infarction in high-intensity exercise-induced heart failure, Shensong Yangxin Capsule dramatically reduces myocardial cell death and cardiac dysfunction. SSYX has a shorter course of treatment and a better therapeutic effect than Sal.

Treatment Outcomes for Tuberculosis Infection and Disease Among Persons Deprived of Liberty, Uganda, 2020.

We report that unsuccessful treatment outcomes were 11.8% for tuberculosis (TB) disease and 21.8% for TB infection among persons deprived of liberty in Uganda Prisons Service facilities. Remedial efforts should include enhancing referral networks to ensure treatment continuity, strengthening data systems for complete outcome documentation, and prioritizing short-course treatment regimens.

Prospective assessment of targeted symptom management on supportive care in cancer: An observational cohort study.

e24073 Background: In advanced cancer, patients may experience treatment-related symptoms or disease burden, necessitating multiple supportive care pharmacotherapies. However, managing these symptoms can lead to complex polypharmacy, potentially resulting in inefficacies or toxicities due to pharmacogenetic interactions. Our study focuses on targeting the most impactful symptom to streamline pharmacotherapy, potentially reducing the need for extensive polypharmacotherapy. By prioritizing management of this "target symptom”, our study seeks to optimize improve overall symptom relief and reduce the need for extensive polypharmacotherapy. Methods: Upon initial palliative care evaluation, the PERSONS score (Pain, Eating/cachexia, Rehabilitation/fatigue, Sleeping disorder, O2/dyspnea, Nausea/emesis, Suffering; each item rated 0-10, total score 0-70) was used to screen for cancer-related symptoms and identify a treatment-specific target symptom for each enrolled patient. Accordingly, a personalized palliative care intervention was implemented based on the identified target. Efficacy of this strategy was then assessed by monitoring changes in the PERSONS score after approximately 10 days of treatment. Non-parametric statistical tests were employed to evaluate differences in symptom distributions between baseline and post-treatment scores: the Wilcoxon signed-rank test for comparisons between two groups and the Kruskal-Wallis test for comparisons across more than two groups. All analyses were conducted using R v4.1. Results: Among 72 prospectively enrolled patients, most had intermediate KPS scores (30-40, 47%; 50-60, 33%) and were not on active treatment (73%); PaP score was A, B and C in 27%, 61% and 11% of patients, respectively. The median PERSONS score at baseline was 26 (range 9 to 51). Pain was identified as the target symptom in 33 (47%) of patients, followed by dyspnea (14%), fatigue (11%), suffering (11%), nausea/emesis (7%) and cachexia (7%). When identified as a target symptom, suffering had numerically higher scores (range, 7-10; Kruskal-Wallis p = .14). PERSONS scores across non-target symptoms were numerically higher in patients with fatigue, pain and nausea/emesis identified as target symptoms. After a median of 9.5 days (range 6 to 138) of targeted treatment, PERSONS scores across non-target symptoms were significantly lower (p = 7.9e-05; median difference = -6, range = -24 to +10), as was intensity of target symptoms (p = 7.2e-14). Conclusions: Focusing on a targeted symptom through a short treatment course not only reduced that specific symptom but also demonstrated clinically significant improvements in non-target symptoms. This comprehensive approach, emphasizing the interconnectedness of symptoms, has the potential to optimize patient care and enhance clinical outcomes in the context of advanced cancer management.

Establishing a protocol to increase racial/ethnic minority enrollment on an active radiation oncology randomized clinical trial.

TPS1638 Background: In the United States (US), underrepresented racial/ethnic groups lack ample enrollment in clinical trials, yielding ungeneralizable trial results. Barriers to increasing minority enrollment include decreased awareness of clinical trials, lack of access, financial burden and toxicity, medical system mistrust, and discordant physician-patient demographics. The ongoing Spine Patient Optimal Radiosurgery Treatment for Symptomatic Metastatic Neoplasms (SPORTSMEN) clinical trial (NCT05617716) has a study design to actively accrue minority patients. We present our protocol addressing key targets to increase minority enrollment on this randomized, phase II clinical trial. Methods: Adults with evidence of symptomatic spine metastases are eligible. Baseline demographics (including race/ethnicity) are reported for statistical analysis. Our protocol seeks to minimize barriers to minority enrollment and targets four key areas. Access to care: SPORTSMEN involves institutions located in zip codes with diverse ethnic populations, presently located in regions 46% and 70% African American. Clinical trial design: SPORTSMEN has a prespecified goal of accruing patients to mirror US census representation. The rate of minority enrollment will be reviewed periodically at the discretion of the Data Safety and Monitoring Board. Community outreach and engagement: The trial team will engage with local health care systems to create an alliance within different oncology specialties to provide the basis and benefit for SPORTSMEN and patient-centered education on eligibility criteria, rationale, and intended outcomes. Our principal focus will be providers in prostate, breast, and lung cancers as minorities with these primary site malignancies have a higher propensity to be trial-eligible. Furthermore, we understand the historical mistrust of minorities for the medical community. Therefore, we will engage local grassroot organizations such as churches, community outreach centers, and social clubs to increase awareness of clinical trials and to help foster trust. Financial burden and toxicity: SPORTSMEN does not have direct enrollment costs. A short-course treatment regimen is used to minimize the number of treatment visits required allowing for decreased resources for travel, time lost at work, and additional childcare or eldercare needs. Financial toxicity will be objectively quantified using the validated COST-Functional Assessment of Chronic Illness Therapy survey. Increasing clinical trial diversity is a challenge that must be addressed with meaningful intent to present robust Level 1 data that broadens the understanding of treatment response in all demographics. Our protocol takes a patient-centered approach to achieve the objective of concordant racial/ethnic representation in a randomized clinical trial. Clinical trial information: NCT05617716 .

The Accessibility, Affordability, and Early Detection of Tuberculosis

Tuberculosis (TB) stands as the leading cause of death from an infectious agent worldwide, with a high fatality rate. It is primarily transmitted through the airborne Mycobacterium tuberculosis (M. tb) from an infected patient to a healthy individual. Annually, millions of people go undiagnosed for TB at an early stage and lose the opportunity for timely treatment, making early TB diagnosis a high priority. Prevalence surveys also have shown that many individuals with lab-confirmed TB disease lack symptoms and do not seek diagnosis or care. Moreover, delays in initiating treatment are commonly observed even after TB diagnosis, heightening the risk of disease transmission in the community. This research paper aims to address these challenges by analyzing the impact of various socioeconomic, policy, and healthcare factors on the accessibility of TB diagnosis. Furthermore, it aims to analyze current effective tuberculosis diagnosis techniques, assessing their strengths and weaknesses. Despite the presence of promising new drugs in the clinical trial stage offering hope for patients with extensively drug-resistant tuberculosis (XDR-TB) or very drug-resistant TB, the primary challenge remains the timely and species-specific detection of Tuberculosis. In addition to the detection of disease, identifying its drug resistance patterns and ensuring the availability of highly active short-course drug treatments are imperative, ideally lasting just a few weeks. This is essential to support the World Health Organization’s (WHO) Global efforts to “END TB” by 2030, to reach 90% of people primarily through early diagnosis, innovative treatments, and vaccine development.

Making Information About Cladribine Tablets Accessible to People with Multiple Sclerosis: A Patient-Survey-Led Narrative Review for Healthcare Professionals.

Cladribine tablets have been granted marketing authorization in Europe and approved by the Food and Drug Administration (FDA) in the USA to treat relapsing forms of multiple sclerosis (MS). However, people with MS (PwMS) may be more familiar, and therefore more confident, with treatments requiring long-term and frequent dosing. Differences in such treatment strategies can lead to questions relating to how short-course non-continuous treatments, such as cladribine tablets, can work and how well they are tolerated. In response to this, we aimed to create an evidence-based report on patient-focused aspects of treatment with cladribine. To inform development, MS experts, including healthcare professionals (HCPs) and PwMS, proposed topics that PwMS and their families and caregivers would most like to discuss with HCPs during consultations to help them better understand cladribine treatment. The statements regarding each topic were then ranked by PwMS and used to inform the topics covered in this report. We explain here the use of cladribine tablets, which includes explanations of how cladribine tablets work, how to take cladribine tablets, and considerations required prior to and while taking cladribine tablets. We also describe how cladribine tablets affect relapse rate and quality of life and detail side effects, when they are likely to happen, and for how long. We also discuss how cladribine tablets affect family planning, fertility, and the use of vaccines. Alongside each section is a brief, plain language description of what is covered and an accompanying visual to aid conversations between HCPs and PwMS. Improved understanding by PwMS of treatments, such as cladribine, can empower them to play a bigger role in shared decision-making regarding their treatment. Additionally, the open dialogue we aim to promote with this type of report could lead to treatment choices being better tailored for individuals with chronic diseases on the basis of personal experiences, preferences, and circumstances.

Multimodal radiotherapy dose prediction using a multi-task deep learning model.

In radiation therapy (RT), accelerated partial breast irradiation (APBI) has emerged as an increasingly preferred treatment modality over conventional whole breast irradiation due to its targeted dose delivery and shorter course of treatment. APBI can be delivered through various modalities including Cobalt-60-based systems and linear accelerators with C-arm, O-ring, or robotic arm design. Each modality possesses distinct features, such as beam energy or the degrees of freedom in treatment planning, which influence their respective dose distributions. These modality-specific considerations emphasize the need for a quantitative approach in determining the optimal dose delivery modality on a patient-specific basis. However, manually generating treatment plans for each modality across every patient is time-consuming and clinically impractical. We aim to develop an efficient and personalized approach for determining the optimal RT modality for APBI by training predictive models using two different deep learning-based convolutional neural networks. The baseline network performs a single-task (ST), predicting dose for a single modality. Our proposed multi-task (MT) network, which is capable of leveraging shared information among different tasks, can concurrently predict dose distributions for various RT modalities. Utilizing patient-specific input data, such as a patient's computed tomography (CT) scan and treatment protocol dosimetric goals, the MT model predicts patient-specific dose distributions across all trained modalities. These dose distributions provide patients and clinicians quantitative insights, facilitating informed and personalized modality comparison prior to treatment planning. The dataset, comprising 28 APBI patients and their 92 treatment plans, was partitioned into training, validation, and test subsets. Eight patients were dedicated to the test subset, leaving 68 treatment plans across 20 patients to divide between the training and validation subsets. ST models were trained for each modality, and one MT model was trained to predict doses for all modalities simultaneously. Model performance was evaluated across the test dataset in terms of Mean Absolute Percent Error (MAPE). We conducted statistical analysis of model performance using the two-tailed Wilcoxon signed-rank test. Training times for five ST models ranged from 255 to 430min per modality, totaling 1925min, while the MT model required 2384min. MT model prediction required an average of 1.82s per patient, compared to ST model predictions at 0.93s per modality. The MT model yielded MAPE of 1.1033±0.3627% as opposed to the collective MAPE of 1.2386±0.3872% from ST models, and the differences were statistically significant (p=0.0003, 95% confidence interval=[-0.0865, -0.0712]). Our study highlights the potential benefits of a MT learning framework in predicting RT dose distributions across various modalities without notable compromises. This MT architecture approach offers several advantages, such as flexibility, scalability, and streamlined model management, making it an appealing solution for clinical deployment. With such a MT model, patients can make more informed treatment decisions, physicians gain more quantitative insight for pre-treatment decision-making, and clinics can better optimize resource allocation. With our proposed goal array and MT framework, we aim to expand this work to a site-agnostic dose prediction model, enhancing its generalizability and applicability.