Discontinuation Of Therapy Research Articles

Mild liver injury following withdrawal of long-term prednisone therapy: A case report

BACKGROUND Liver injury manifesting as hepatic enzyme abnormalities, has been occasionally identified to be a feature of primary or secondary Addison's disease, an uncommon endocrine disease characterized by adrenal insufficiency. There have been no more than 30 reported cases of liver injury explicitly attributed to Addison's disease. Liver injury resulting from adrenal insufficiency due to glucocorticoid withdrawal is exceptionally rarer. CASE SUMMARY A 42-year-old man presented with fatigue and mildly elevated transaminases. Laboratory investigations and imaging studies excluded common etiologies of liver injury. Based on the fact that the patient discontinued long-term therapy with prednisone approximately 2 weeks before he was found to have elevated transaminase levels and the observation that his cortisol was lower than the normal value, he was diagnosed as having hypertransaminasemia secondary to adrenal insufficiency caused by glucocorticoid withdrawal. The patient was infused intravenously with compound diisopropylamine dichloroacctate and compound glycyrrhizin, and his transaminase levels returned to normal after 1 week. Approximately 2 years later, the patient received hydroprednisone treatment for 2 days in an endoscopic sinus surgery. Eight days after he discontinued the hydroprednisone treatment, he developed symptoms reminiscent of glucocorticoid withdrawal syndrome. These symptoms resolved spontaneously after 1 week. Intriguingly, the patient did not develop hepatic dysfunction this time. CONCLUSION The present case, showing some unusual clinical features, highlights the importance of education of clinicians and patients to avoid improper discontinuation of glucocorticoid therapy and complete history taking for prompt recognition.

DISCOntinuation of disease-modifying therapies in MS: The DISCOMS extension trial.

In the DISCOMS (DISCOntinuation of disease-modifying therapies (DMTs) in multiple sclerosis (MS)) randomized clinical trial, we could not demonstrate that discontinuing MS DMTs in older, stable adults was not inferior to continuing DMTs. Relapses were rare in both groups, and most new disease activity was one to two new brain magnetic resonance imaging (MRI) lesions unassociated with clinical changes. Describe results of the DISCOMS extension study. Among 10/19 of the original sites, we enrolled patients who completed DISCOMS; did not reach the primary endpoint during the original trial; and retained original randomized assignment. Participants completed one study visit and brain MRI at least 30 months after original enrollment in DISCOMS. Primary endpoint was time from entry into the primary study to relapse or new brain MRI activity. Mean (SD) total follow-up was 40 (11.7) months. There were no relapses, and new brain MRI lesions (1/30 continuer, 2/44 discontinuers) were uncommon during the extension. Time from primary trial entry to disease event was significantly shorter for subjects in the discontinue group (p = 0.043 from log-rank test). From entry into DISCOMS extension study, time to new MS activity remained shorter in discontinuers, but relapses were absent and new brain MRI lesions were rare.

Sex-specific DNA methylation marks associated with sex-biased risk of recurrence in unprovoked venous thromboembolism.

Whether to stop oral anticoagulants after a first unprovoked venous thromboembolism (VTE) is challenging, partially due to an intriguingly higher risk of VTE recurrence (rVTE) in men after therapy discontinuation. DNA methylation (DNAm) differences between men and women might underly this sex-biased rVTE risk difference. To investigate sex-specific associations between DNAm at cytosine-phosphate-guanine (CpG) sites and rVTE. In 417 unprovoked VTE patients, including 101 experiencing recurrences over 5-year follow-up (REVERSE I), we analyzed blood DNAm using the Illumina EPIC array and performed a sex-stratified epigenome-wide association study. We further examined 181 major provoked VTE patients, including 36 recurrences over 14-year follow-up (MARTHA), to investigate whether DNAm are risk factors for rVTE after anticoagulation therapy. Hypomethylated CpGs at genes TBC1D22B-cg01060850 and ZHX2-cg07808424 in men and DIP2B-ch.12.1038646R and DENND3-cg03401656 in women were associated with rVTE at genome-wide level (p<7e-8). Though not statistically significant, DENND3-cg03401656 had the same direction of effect in MARTHA women. Sensitivity analysis confirmed the robustness of the estimates including potential confounders, adaptations of the Cox model, non-Europeans, and proximal methylation quantitative trait loci (meQTLs) in the association. The associated CpGs were situated at genes for membrane trafficking, corroborating the participation of Rab regulatory proteins in rVTE, and transcription factors. We identified DNAm marks as potential risk factors for sex-biased recurrence in unprovoked VTE. Further replication and experimental validation could refine our understanding on the regulation of the identified DNAm sites and help optimize personalized decision-making for long-term anticoagulation after first VTE.

Retrospective evaluation of dexamethasone for treatment of suspected critical illness-related corticosteroid insufficiency in dogs with septic shock (2017-2022): 60 cases.

To retrospectively compare and report vasopressor duration and mortality of septic dogs with hypotension refractory to vasopressor administration (presumed critical illness-related corticosteroid insufficiency [CIRCI]) treated with or without dexamethasone sodium phosphate (DxSP). Retrospective study (2017-2022). Tertiary referral and teaching hospitals. Sixty client-owned dogs with confirmed or presumed sepsis and vasopressor-resistant hypotension. Hypotension was defined as systolic arterial pressure < 90mmHg or MAP < 65mmHg. Vasopressor resistance was defined as hypotension despite therapy with moderate- to high-dose vasopressors (> 0.5µg/kg/min of norepinephrine IV). None. Twenty-six dogs received DxSP (DxSP group, 0.002-0.39mg/kg IV, variable frequency), and 34 dogs did not receive a glucocorticoid (non-DxSP group). The median time to vasopressor discontinuation was 20hours (interquartile range [IQR]: 21; n=6) in the DxSP group and 27 hours (IQR: 11; n=5) in the non-DxSP group. In the DxSP group, 23% (6/26) of dogs survived to discharge compared with 15% (5/34) of dogs in the non-DxSP group, which was not significantly different (relative risk: 0.90, 95% confidence interval: 0.70-1.16; P=0.41). There was no significant difference between the 2 groups in time from vasopressor administration to weaning in dogs that survived to discharge (P=0.43). The median time from steroid administration to vasopressor wean was 15 hours (IQR: 19; n=6), and the median time from steroid administration to sustained normotension (a systolic blood pressure > 90mmHg or a MAP>65mmHg for at least 4h) was 1 hour (IQR: 5; n=11). There was no association between DxSP therapy and survival, duration of vasopressor therapy, or time between steroid administration and discontinuation of vasopressor therapy in dogs being treated for sepsis, vasopressor resistance, and suspected CIRCI.

COVID-19-Related Discontinuation Impact on Patient-Reported Outcomes in Long-Term Thermal Therapy: A Single-Center Observational Study at Saturnia Thermal Springs.

Thermal therapy represents a well-established therapeutic approach for chronic musculoskeletal and respiratory conditions. To date, no studies have investigated the clinical effects of treatment interruption in thermal medicine. We aimed to evaluate the clinical impact of COVID-19 lockdown-induced thermal therapy discontinuation through validated patient-reported outcomes. This single-center observational, retrospective study (March 2020-June 2024) evaluated 97 patients receiving standardized thermal therapy at Saturnia Thermal Springs. Treatment protocols included balneotherapy, mud therapy, and inhalation treatments in cycles of 12-15 sessions, with maintenance protocols every 4-6 months. Primary outcomes were assessed through VAS and SF-36 PCS, with EQ-5D and PSQI as secondary outcomes. Significant clinical deterioration occurred during treatment interruption (p < 0.001) in 77.7% of patients. Recovery patterns were duration-dependent, with the 6-7-year cohort showing faster recovery (mean time to baseline: 2.8 months) compared to the 3-5-year cohort (4.6 months). Effect sizes were substantial across all outcomes (Cohen's d > 1.0), with EQ-5D scores showing duration-dependent improvement (mean improvement in 6-7-year cohort: 0.27). Thermal therapy interruption precipitates quantifiable clinical deterioration, with recovery patterns significantly influenced by pre-existing treatment duration. These findings support the essential nature of treatment continuity in thermal therapy protocols.

The response to pericapsular soft tissue and pelvic realignment therapy may be partially predicted by the relevant factors influencing the program’s response of the candidates with hip osteoarthritis for joint replacement

Objective To explore the risk factors for discontinuation of pericapsular soft tissue and pelvic realignment (PSTP-R) therapy derived from Shiatsu in the candidates with osteoarthritis for total hip replacement (THR) (i.e., candidates for total hip replacement) treated from 2017 to 2020, and to identify the effect modifiers of PSTP-R therapy for patients who continued therapy for 6 months. Methods Exploratory analyses of data from the clinical trial for PSTP-R therapy in a prospective observational study in which the PSTR exercises for 6 months improved Harris Hip Score (HHS) in 193 patients with an HHS below 60 points in two study centers, even in 130 patients with complete loss of cartilage on radiography among those 193 ones. The risk factors for the discontinuation of PSTP-R therapy and the effect modifiers for PSTP-R therapy were explored statistically. Results The risk of discontinuation of PSTP-R therapy increased as the frequency of buttock pain at baseline increased, and was mitigated as the baseline opening angle of the hip according to the modified Patrick’s test increased. Cartilage loss on radiography was not a risk factor for withdrawal from PSPT-R therapy. Among patients who continued PSTP-R therapy for 6 months, a lower Kellgren-Lawrence grade at baseline was associated with an increase in the total score of HHS. Conclusion Buttock pain at baseline was most associated with discontinuation of PSPT-R therapy. The patients that can improve with PSPT-R therapy should be selected to avoid inappropriate surgery by the detailed analysis of relevant clinical factors influencing the response for this program as well as image findings such as cartilage loss on radiography at baseline. Trial registration Registered in the Clinical Trials Registry on 20th July 2017 (UMIN000028277).

Meta-Analysis: Exclusive Enteral Nutrition in Adults With Ulcerative Colitis.

Exclusive enteral nutrition (EEN) is an established dietary therapy for Crohn's disease but its role in ulcerative colitis remains unclear. To investigate the efficacy of EEN in adults with active ulcerative colitis and compare variations in treatment protocols, safety, tolerability and adherence. We conducted a systematic search of MEDLINE, Embase, Cochrane CENTRAL, Emcare, CINAHL, Web of Science and trial registries for articles published from inception until July 21, 2024. We included all experimental and observational studies that described the use of EEN in adults with active ulcerative colitis. This review was registered on PROSPERO (CRD42022319584). Of 3273 articles screened, we included 10 studies (334 adults). Overall, there was no difference between EEN and comparator for ulcerative colitis remission induction (median follow-up 14 days, risk ratio (RR) 1.15, 95% confidence interval (CI) 0.71-1.85; 2 studies). In acute severe ulcerative colitis, there was no difference between EEN and comparator for corticosteroid failure (RR 0.76, 95% CI 0.48-1.20; 2 studies) or risk of colectomy (RR 0.88, 95% CI 0.51-1.51, n = 2 studies) during index admission. The pooled discontinuation rate was 3% (95% CI 0-10; 9 studies). There was heterogeneity in trial design, methodology and assessment of outcomes. EEN was well tolerated with low therapy discontinuation in adults with active ulcerative colitis. However, there is insufficient evidence to support the use of EEN as an adjunctive therapy to standard of care. Further, well-designed studies with reproducible methodology and endpoints are necessary to evaluate its effectiveness. PROSPERO 2022 CRD42022319584.

Management of Children with Heterozygous Familial Hypercholesterolemia Worldwide: A Meta-Analysis

Abstract Background Heterozygous familial hypercholesterolemia (HeFH) is one of the most frequent monogenic disorders in the world, leading to premature atherosclerotic cardiovascular diseases (ASCVD). The aim of this meta-analysis was to evaluate the efficacy and safety of lipid lowering therapy (LLT) and achievement of low-density lipoprotein cholesterol (LDL-C) goal in children with HeFH. Methods The main endpoint was efficacy of goal achievement for LDL-C and other lipid parameters: total cholesterol [TC], triglycerides [TG], high density lipoprotein cholesterol [HDL-C], apolipoprotein B [apo B] and lipoprotein(a) [Lp(a)]), and the LLT safety (adverse events [AEs], including endocrine function, and growth indices). The secondary endpoint was an effect of LLT on attainment of LDL-C goal treatment (&amp;lt;3.5 mmol/L/130 mg/dL). Results A total of 41 studies with 4667 pediatric patients at mean age 12.08±2.4 years were included. 17 reported the efficacy and safety of LLT therapy compared to control, while the remaining assessed LLT through pre- and post-treatment. At median follow-up of 18.8 months, the group on LLT had significantly higher mean reductions of TC, LDL-C, TG, and increased HDL-C compared to control (-1.75 [-67,7 mg/dl], -1.84 [-71.2 mg/dl], -0.11 [-9.74 mg/dl], 0.08 mmol/L [3.1 mg/dl], respectively, p&amp;lt;0.001 for all). In the subgroup analysis according to different types of LLT we observed a significantly higher mean reduction of LDL-C by statin combined with ezetimibe treatment, followed by statins in monotherapy, PCSK9 inhibitors, and monotherapy with ezetimibe (-2.48 [-95.9 mg/dl], -2.16 [-83.5 mg/dl], -2.03 [-78.5 mg/dl], and -1.50 mmol/L [-58 mg/dl], respectively, test for overall effect: p&amp;lt;0.001). The pooled LDL-C was reduced by 33.44% (-2.14 mmol/L [-82.8 mg/dl], p&amp;lt;0.001) and failed to reach the goal treatment (&amp;lt;3.5 mmol/L) by 12.6% (95%CI, 12.4–12.9%). 38.7% of children achieved the LDL-C goal, 23.9% fell short by up to 10%, 10.7% experienced moderate failure (were over the LDL-C target between &amp;gt;10-20%), and 26.7% failed by more than 20% to reach the LDL-C target. When comparing different regions, only Sweden and Greece achieved the LDL-C goal &amp;lt;3.5 mmol/L in the follow-up, followed by the Netherlands, Norway, Poland, USA, UK, France, Spain, Belgium, and Austria (with the following additional required LDL-C reduction to be on the goal: 2.2%, 3.4%, 3.5%, 8.9%, 10.2%, 11.2%, 11.2%, 15%, 19.4%, respectively). For other investigated countries over 20% mean LDL-C reduction was required. All parameters related to endocrine function and demographic indices were unaffected by LLT therapy (p&amp;gt;0.05). The adverse events were not reported significantly higher when compared to the control and the prevalence of therapy discontinuation was only 0.8%. Conclusions Despite the efficacy of LLT in children with HeFH and the low occurrence of discontinuation-related adverse events, achieving LDL-C treatment goals was relatively rare, with large differences between the investigated countries. These results underscore the importance of considering early combination therapy of statins and ezetimibe, and PCSK9 inhibitors (if available) to attain LDL-C goals effectively.

Ultrasound-guided Transperineal Prostate Thermal Ablation (TPTA) for Benign Prostatic Hyperplasia: Feasibility of an Outpatient Procedure using Radiofrequency Ablation.

To evaluate the feasibility, safety, and short-term (3-month) results of transperineal prostate thermal ablation (TPTA) as a minimally invasive outpatient treatment for benign prostatic hyperplasia (BPH). A prospective nonrandomized study of 25 patients with lower urinary tract symptoms secondary to BPH seeking care at 2 interventional radiology centers between March and July 2024. TPTA was performed using a 17G radiofrequency needle with a 10-mm active tip under unconscious sedation combined with bilateral perineal and periprostatic nerve blocks. The primary outcome measure was technical success, defined as successful bilateral ablation of the prostate transition zone. Secondary outcome measures included changes of international prostate symptom score (IPSS), quality of life (QoL), prostate volume, intravesical prostatic protrusion (IPP), prostate-specific antigen (PSA), post-void residual volume (PVR), maximum urinary flow rate (Qmax), and need for BPH medical therapy at 3months relative to baseline. All procedures were technically successful (100%). The median patient age was 69.4years (IQR 54-74), and all were discharged within 3h of the end of the procedure. Sixteen patients (64.0%) were discharged without a urinary catheter, and 6 patients (24.0%) reported mild complications. At 3-month follow-up, there were significant reductions in IPSS (79.1%), QoL score (70.3%), prostate volume (36.9%), IPP (70.8%), PSA (54.7%), and PVR (51.1%), whereas Qmax increased significantly (102.3%). Twenty-four patients (96.0%) reported discontinuation of medical therapy after TPTA. Ultrasound-guided TPTA using radiofrequency ablation is feasible and safe in the outpatient setting, with significant clinical improvements after 3months of the procedure. Level 3 [non-randomized prospective cohort study].

Incomplete Toxicity Reporting and Use of Toxicity-Minimizing Language in Phase III Oncology Trials.

This study aimed to determine complete toxicity reporting (CTR), and the use of subjective toxicity-minimizing language (TML) among phase III oncology trials. Two-arm superiority-design phase III oncology trials published from 2002 to 2020 were reviewed for toxicity data. CTR was defined as reporting total adverse events (TAEs), total serious adverse events (SAEs), total deaths, and study therapy discontinuations because of toxicity. Guideline concordance was defined according to guidelines published in the BMJ (defined as reporting total SAEs, total deaths, and study therapy discontinuations because of toxicity). TML was defined as a set of terms that subjectively downplay the harm of therapies. A total of 407 trials enrolling 322,645 patients were included. Most (51%, n = 207) reported SAEs, 88% (n = 358) reported total deaths, and 84% (n = 340) reported study therapy discontinuation because of toxicity. Although 55% of trials (n = 223) reported TAEs, only 32% (n = 131; 95% credible interval, 28 to 37) fit the criteria for CTR. CTR was more common in trials with industry sponsorship (37%) than with cooperative group sponsorship (4%). All 131 trials where CTR was observed were industry-sponsored, and only 3% (4/131) were cooperative group-sponsored trials. TML was used in 46% of trials (n = 186; 95% credible interval, 41 to 51), with no trial-related factors (including sponsorship source) associated with the odds of TML use. Toxicity in phase III oncology clinical trials is often incompletely reported and is frequently minimized in its interpretation. Industry-sponsored trials more comprehensively report toxicity than do cooperative group-sponsored trials. CTR may improve patients' and oncologists' understanding of new treatments; thus, a more standardized approach to reporting toxicity data is needed.

BRAF inhibitor monotherapy in BRAFV600E-mutated pediatric low-grade glioma: a single center's experience.

Pediatric low-grade gliomas (pLGGs) have an overall survival of over 90%; however, patients harboring a BRAFV600E alteration may have worse outcomes, particularly when treated with classic chemotherapy. Combined BRAF/MEK inhibition following incomplete resection demonstrated improved outcome in BRAFV600E altered pLGG compared to combined carboplatin/vincristine chemotherapy and is now considered the standard FDA-approved treatment for this group of tumors. The aim herein was to investigate the efficacy and tolerability of single agent BRAF inhibitor treatment in BRAFV600E altered pLGG. A single institution retrospective chart review analysis was performed on patients, 0 to 21 years of age, with newly diagnosed and/or progressive BRAFV600E mutated pLGGs (WHO Grade 1 or 2) at Children's Healthcare of Atlanta treated off-study with BRAF inhibitor monotherapy between 2013-2023. 2-year progression free survival (PFS) and objective tumor response was evaluated. All toxicities possibly associated with BRAF inhibition therapy were evaluated and described according to Common Terminology Criteria for Adverse Events version 5 (CTCAEv5). MRI brain imaging data at baseline and best response wasevaluated to identify patterns that may predict response to BRAF inhibition monotherapy. Fifteen patients diagnosed with BRAFV600E mutated pLGG, treated with monotherapy BRAF inhibition, were identified. Median age of diagnosis: 3.8 years (0.2 -18.1). Histologic diagnosis: pilocytic astrocytoma (PA) (N=4); ganglioglioma (GGL) (N=3); GGL, atypical (N=3); pleomorphic xanthroastrocytoma (PXA) (N=2); low-grade neuroepithelial tumor (N=1); infiltrating glioma (N=1); and LGG (NOS) (N=1). Tumor locations included: hypothalamus/optic chiasm (N=6); brainstem (N=4); third ventricle/thalamus (N=2); parietal/temporal lobe (N=2); and spinal cord (N=1). Mean duration of BRAF inhibitor monotherapy: 38.41 months (range 3.9-83.7). Median follow-up: 32.6 months (16 - 78.1). Two-year PFS for patients on BRAFi monotherapy for at least 10 months: 90% (95% CI: 73.2%-100%). Objective Response (OR) for 15 evaluable patients on BRAF inhibitor (BRAFi) therapy: 73% (0/15 CR + 6/15 PR + 5/15 MR) with Overall Response Rate (ORR=CR+PR): 40%. Overall, patients tolerated treatment well with Grade 1 rash being the most common toxicity. Two of 15 patients (13%) discontinued therapy due to toxicities, and 2 other patients switched within drug class from vemurafenib to dabrafenib due to toxicities. In this small cohort of incompletely resected BRAFV600E mutated pLGGs, BRAFi monotherapy was effective and well tolerated with an ORR comparable to published prospective outcomes of dual MEK/BRAF inhibitor therapy. This promising monotherapy treatment should be considered when choosing treatment for incompletely resected BRAFV600E-altered pLGGs.

Application of low-dose FDG-PET/MRI for quantification of lung changes in pediatric patients with cystic fibrosis: a new inflammatory index.

Clinical severity and progression of lung disease in cystic fibrosis (CF) are significantly influenced by the degree of lung inflammation. Non-invasive quantitative diagnostic tools are desirable to differentiate structural and inflammatory lung changes in order to help prevent chronic airway disease. This might also be helpful for the evaluation of longitudinal effects of novel therapeutics. Therefore, the present study assesses the quantification of inflammatory lung changes using positron emission tomography/magnetic resonance imaging (PET/MRI) of the lung in children and adolescents with CF and evaluates the possible impact of PET/MRI on individualized therapy management. This monocentric, retrospective cohort study included 19 PET/MRI of the lung performed between 2014 and 2021 in 11 patients (16±4.5 years, 8-22 years; 7 females). PET acquisition was performed at least 20 minutes after i.v. application of a weight-adjusted dose of fluor-18-fluorodeoxyglucose (18F-FDG) of 1 MBq/kgBW (mean effective dose, 1.3±0.4 mSv). Lesions of increased uptake were quantified based on standardized uptake values (SUV) and compared to background activity, liver and blood pool. Pulmonary changes were assessed using the established magnetic resonance imaging-CF (MR-CF) score and correlated to inflammatory lesions. Results were correlated to changes in therapy (initiation, modification or discontinuation of therapy after baseline-PET/MRI) based on the electronic medical records. Uptake was highly increased in 5 cases, moderate in 4 cases, low in 7 cases, no uptake in 3 cases. Most MR-CF score points were assigned to peribronchitis (23%) and air trapping (23%). Metabolically increased lesions were mainly interpreted as consolidations (59%; P<0.001) and mucus plugging (19%, P=0.024). There was a decrease in mean number and volumes of inflammatory lesions (P=0.016 each) and MR-CF score (P=0.047) between baseline and follow-up. After PET/MRI, therapy changed in 18 cases (95%; new medication: 58%, n=11; termination of therapy: 16%, n=3; modification of therapy: 21%, n=4). In selected cases, pulmonary FDG-PET/MRI can help guide therapeutic decision-making and provide complementary information on CF-related lung changes to conventional MRI at a low radiation exposure.

Opioid agonist therapy discontinuation in British Columbia: a cross-sectional study of people who access harm reduction services

ObjectivesThis study evaluates the prevalence and correlates of opioid agonist therapy (OAT) discontinuation across British Columbia (BC), using a sample of individuals who used substances and accessed harm reduction sites.DesignThis...

Clinical course and radiographic resolution of pneumonia in dogs treated with a shorter versus longer course of antimicrobials: a randomized, double-masked, placebo-controlled study.

To describe clinical and radiographic outcomes in dogs with uncomplicated pneumonia receiving a shorter (2-week) versus longer (4-week) duration of antimicrobial therapy. 30 client-owned dogs with radiographic evidence of pneumonia. Dogs were randomly assigned to either a 2-week course of antimicrobials followed by a 2-week course of placebo medication (2-week group) or a 4-week course of antimicrobials (4-week group). All study investigators and owners were masked to the treatment group. Dogs were reevaluated at 12 ± 2 days and again at 28 ± 2 days for a physical examination and thoracic radiography. Standard documentation at visits included owner-reported clinical signs, nurse-acquired history, the clinician's physical examination, the number of affected lung lobe segments, and the global radiographic severity scores assigned. Outcomes investigated included the persistence of clinical and radiographic signs of pneumonia. 28 dogs (93.3%) experienced complete resolution of clinical signs by the first visit, and no dogs in either group experienced relapse of clinical signs during the study period. Eighteen of 30 dogs (60%) and 25 of 30 dogs (83%) experienced complete resolution of radiographic lesions at the first and second study visits, respectively. The remaining 5 dogs (17%) had either stable (4 dogs) or continued (1 dog) improvement in radiographic lesions. Resolution of clinical and radiographic signs followed similar courses in dogs with uncomplicated pneumonia receiving a 2-week course of antimicrobials compared to a 4-week course. Clinical signs may be more useful for guiding discontinuation of antimicrobial therapy for pneumonia than radiographic signs.

Yield of clinical metagenomics: insights from real-world practice for tissue infections.

While metagenomic next-generation sequencing (mNGS) has been acknowledged as a valuable diagnostic tool for infections, its clinical validity and impact on patient management when using fresh tissue samples remains uncertain. We conducted a retrospective cross-sectional study involving patients who underwent tissue mNGS at a tertiary hospital in China from February 2021 to February 2024, aiming to assess its ability to detect plausible pathogens and its clinical validity and impact. A total of 520 mNGS results from 508 patients were analysed, detecting plausible pathogens in 302 (58.1%) tests, including 260 single-pathogen and 42 (13.9%) multi-pathogen results. Rare pathogens, such as Balamuthia mandrillaris, Bartonella henselae, and Sporothrix globosa, were identified. Of the multi-pathogen results, 22 were with predominance of anaerobes. mNGS showed higher positivity in cases with high initial suspicion of infection than those used for ruling out infection (PR 1.961, 95% CI: 1.604-2.394) and in patients living with HIV (PR 1.312, 95% CI: 1.047-1.643) or solid organ transplant recipients (PR 1.346, 95% CI: 1.103-1.643) compared to immunocompetent individuals. Sensitivity and specificity for diagnosing confirmed/probable infections were 85.0% (95% CI: 76.7%-93.3%) and 93.7% (95% CI: 86.8%-100.0%), respectively. mNGS influenced clinical management in 258 (49.6%) cases by identifying new infections and in 112 (21.5%) by excluding infections. It prompted initiation (20.2%), modification (23.1%), or discontinuation (6.3%) of antimicrobial therapy. mNGS demonstrates high diagnostic accuracy for tissue infections. Its impact on clinical management highlights the need to integrate it into current diagnostic practices. National Natural Science Foundation of China (No. 82472371), "Leading Geese" Research and Development Plan of Zhejiang Province (No. 2024C03218), and Pudong New Area Joint Project (PW2021D-09).

Initial Decline in Glomerular Filtration Rate With Finerenone in HFmrEF/HFpEF: A Prespecified Analysis of FINEARTS-HF.

An initial decline in estimated glomerular filtration rate (eGFR) often leads to reluctance to continue life-saving therapies in patients with heart failure (HF). The goal of this study was to describe the association between initial decline in eGFR and subsequent clinical outcomes in patients randomized to placebo or finerenone. In this prespecified analysis of FINEARTS-HF (Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients with HeartFailure), we examined the association between initial decline in eGFR (≥15%) from randomization to 1month and subsequent outcomes in patients assigned to finerenone or placebo. The primary outcome was the composite of total HF events and cardiovascular death. Among 5,587 patients with an eGFR measurement at both baseline and 1month, 1,018 (18.2%) experienced a≥15% decline in eGFR. The proportion of patients experiencing a≥15% decline in eGFR was 23.0% with finerenone and 13.4% with placebo (OR: 1.95; 95%CI: 1.69-2.24; P< 0.001). After adjustment, an eGFR decline was associated with a higher risk of the primary outcome in patients assigned to placebo (adjusted rate ratio: 1.50; 95%CI: 1.20-1.89) but not in those assigned to finerenone (adjusted rate ratio: 1.07; 95%CI: 0.84-1.35; Pinteraction=0.04). By contrast, the efficacy of finerenone was consistent across the range of change in eGFR from baseline to 1month (Pinteraction=0.50 for percent change in eGFR), and safety, including hyperkalemia, was similar regardless of an early eGFR decline. Although an initial decline in eGFR was associated with worse outcomes in patients assigned to placebo, this relationship was not as strong in those treated with finerenone. An early decline in eGFR can be anticipated with finerenone and should not automatically lead to the discontinuation of this disease-modifying therapy (FINEARTS-HF Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients with HeartFailure [NCT04435626]; A Multicenter, Randomized, Double-Bline, Parallel-Group, Placebo-Controlled Study to Evaluate the efficacy and safety of finerenone on morbidity and mortality in participants With HeartFailure [NYHA II-IV] and left ventricular ejection fraction≥40% [EudraCT 2020-000306-29]).

Effects of individualized nurse-led care plans on olaparib treatment duration.

To assess the effects of a nurse-led personalized care plan on the duration of olaparib therapy among patients with cancer. Cohort study conducted from January 2020 to June 2022. Data from an independent specialty pharmacy were used to identify patients 18 years and older with at least 1 olaparib (Lynparza) prescription who were at high risk for olaparib nonadherence as assessed using a pharmacy intake survey. We compared olaparib therapy duration between patients with and without a nurse-led personalized care plan. Multivariable Cox proportional hazards regression was used to estimate adjusted HRs (aHRs) for therapy discontinuation. Of 560 patients at high risk for olaparib nonadherence, 163 received a care plan and 397 did not. Commonly reported symptoms included fatigue, nausea, gastrointestinal tract problems, depression, anxiety, and pain. The care plan group had significantly longer olaparib therapy (median [IQR], 6.7 [2.5-14.3] months vs 4.9 [1.9-10.4] months; P < .001) and a lower risk of discontinuing treatment (aHR, 0.77; 95% CI, 0.64-0.94) than the controls. Within the care plan group, patients experiencing resolution of at least 1 symptom (median therapy duration [IQR], 10.3 [4.8-19.0] months vs 3.9 [1.9-11.4] months; P < .001) or at least 1 dose modification (median therapy duration [IQR], 11.9 [6.7-17.8] months vs 4.7 [1.9-11.8] months; P < .001) had approximately 2.5 times longer olaparib therapy duration than patients who did not. A nurse-led personalized care approach effectively increased medication persistence among patients receiving olaparib for treatment of cancer, and the effect was more apparent among care plan patients who experienced symptom resolution or dose modification.

Self-acupressure for patients with breast cancer experiencing aromatase inhibitor-associated musculoskeletal symptoms: Protocol for the AcuAIM randomized pilot trial.

Aromatase inhibitors (AI) reduce hormone receptor-positive breast cancer recurrence risk by about 50%. However, half of AI-treated postmenopausal women report new or worsened musculoskeletal symptoms (AIMSS), and 20% discontinue therapy prematurely. Acupuncture is effective for reducing symptoms, but many women are not able to access acupuncture therapy. We hypothesize that self-administered acupressure will reduce AIMSS. Postmenopausal women who have been receiving treatment with an AI for more than 3 weeks but less than 2 years, and who report new or worsened joint pain or myalgias since starting AI therapy with worst pain of at least 4 out of 10 on a numerical rating scale, are eligible. Fifty participants will be enrolled and randomized 1:1 to treatment with true or sham acupressure for 12 weeks. Participants will self-apply pressure for 3 minutes to each of the 9 acupoints daily. All participants will complete a pain assessment weekly, and a battery of symptom questionnaires every 6 weeks. Optional stool samples will be collected after 0 and 12 weeks of acupressure to examine changes in the gut microbiome. The primary endpoint is change in worst pain on the Brief Pain Inventory-Short Form with 12 weeks of the acupressure intervention, evaluated with generalized estimating equations. Determination that self-administered acupressure reduces AIMSS in this randomized phase 2 pilot trial will lead to a larger randomized phase 3 clinical trial to confirm the efficacy of self-acupressure. Reduction of AI-related arthralgias may improve persistence with breast cancer therapy, breast cancer outcomes, and quality of life for AI-treated patients. Clinicaltrials.gov NCT06228768.

Effect of balloon pulmonary angioplasty on chronic thromboembolic pulmonary hypertension: an assessment of the learning curve in a Japanese university hospital

Abstract Balloon pulmonary angioplasty (BPA) is an innovative treatment for chronic thromboembolic pulmonary hypertension (CTEPH). We retrospectively examined the clinical outcomes and complications of BPA at Yokohama City University Hospital (YCUH) between 2012 and 2018. In 2012, we began to conduct BPA sessions in 46 patients with inoperable CTEPH; 34 completed the BPA scheme and the follow-up plan. A longitudinal sub-analysis was performed with cohorts 1 and 2 receiving BPA before and after April 2015. Significant improvements in the mean pulmonary arterial pressure, pulmonary vascular resistance, and other parameters were detected after BPA. The total rate of thoracic complications was 25%. Specifically, the increase in SaO2 and home oxygen therapy discontinuation rate, and oral riociguat discontinuation rate was significantly higher in cohort 2 (+ 7.7, 75, and 59%) compared to cohort 1 (+ 3.1, 27, and 10%) (P &lt; 0.05). Moreover, the need for non-invasive positive pressure ventilation was significantly lower: 0% (cohort 2) vs. 7% (cohort 1) (P &lt; 0.05). The BPA sessions conducted at the YCUH resulted in significant improvements in patients with CTEPH. This study demonstrates a clear learning curve regarding the effectiveness of BPA both in normalizing SaO2 and facilitating the cessation of home oxygen therapy, as well as in reducing the incidence of severe complications. Graphical abstract

Non-adherence, discontinuation, and seroconversion among people on daily HIV pre-exposure prophylaxis (PrEP) in Brazil: a nationwide cohort study

ABSTRACT The goal of this study was to evaluate characteristics associated with Pre-exposure Prophylaxis for HIV infection (PrEP) non-adherence or discontinuation in Brazil and assess the association between these outcomes and HIV seroconversion. We used linked national dispensing and pathology data to identify people aged 14+ years initiating PrEP in 2018. We estimated non-adherence using the proportion of days covered (PDC), defining non-adherence as PDC < 60%. We defined discontinuation as a gap in therapy of at least 120 days. We used logistic regression models to assess characteristics associated with non-adherence or discontinuation within 365 days and to assess HIV seroconversion and its association with non-adherence or discontinuation. In 2018, 5100 people initiated PrEP; 34.4% (95%CI 33.1%; 35.7%) were non-adherent and 34.3% (95%CI 33.0%; 35.6%) discontinued. People aged 34 years or less, women, people with lower education levels, or living in the Northern region of Brazil were more likely to be non-adherent or discontinue therapy. Thirty people (0.6% 95%CI 0.4%; 0.8%) seroconverted. HIV seroconversion was associated with PrEP non-adherence or discontinuation (OR = 6.2 for both). Non-adherence and discontinuation were common in people initiating PrEP and strongly associated with HIV seroconversion. Our work identifies populations at higher risk of non-adherence or discontinuation which could be targeted in interventions to reduce new HIV cases in Brazil.