Long-Term Oxygen Therapy for 24 or 15 Hours per Day in Severe Hypoxemia.

BACKGROUND: Long-term oxygen supplementation for at least 15 hours per day prolongs survival among patients with severe hypoxemia. On the basis of a nonrandomized comparison, long-term oxygen therapy has been recommended to be used for 24 hours per day, a more burdensome regimen. METHODS: To test the hypothesis that long-term oxygen therapy used for 24 hours per day does not result in a lower risk of hospitalization or death at 1 year than therapy for 15 hours per day, we conducted a multicenter, registry-based, randomized, controlled trial involving patients who were starting oxygen therapy for chronic, severe hypoxemia at rest. The patients were randomly assigned to receive long-term oxygen therapy for 24 or 15 hours per day. The primary outcome, assessed in a time-to-event analysis, was a composite of hospitalization or death from any cause within 1 year. Secondary outcomes included the individual components of the primary outcome assessed at 3 and 12 months. RESULTS: Between May 18, 2018, and April 4, 2022, a total of 241 patients were randomly assigned to receive long-term oxygen therapy for 24 hours per day (117 patients) or 15 hours per day (124 patients). No patient was lost to follow-up. At 12 months, the median patient-reported daily duration of oxygen therapy was 24.0 hours (interquartile range, 21.0 to 24.0) in the 24-hour group and 15.0 hours (interquartile range, 15.0 to 16.0) in the 15-hour group. The risk of hospitalization or death within 1 year in the 24-hour group was not lower than that in the 15-hour group (mean rate, 124.7 and 124.5 events per 100 person-years, respectively; hazard ratio, 0.99; 95% confidence interval [CI], 0.72 to 1.36; 90% CI, 0.76 to 1.29; P = 0.007 for nonsuperiority). The groups did not differ substantially in the incidence of hospitalization for any cause, death from any cause, or adverse events. CONCLUSIONS: Among patients with severe hypoxemia, long-term oxygen therapy used for 24 hours per day did not result in a lower risk of hospitalization or death within 1 year than therapy for 15 hours per day. (Funded by the Crafoord Foundation and others; REDOX ClinicalTrials.gov number, NCT03441204.).

Duration of anticoagulation of venous thromboembolism.

Venous thromboembolism (VTE) is a common, serious condition that requires anticoagulation for at least three months to prevent recurrence and long-term complications. After this initial period, the decision to continue or stop anticoagulation depends on the balance between the risk of recurrent VTE and the risk of bleeding. Established guidelines suggest short-term anticoagulation for VTE caused by transient factors and indefinite anticoagulation for recurrent or cancer-associated VTE. However, for a first unprovoked VTE, decision-making remains challenging. Current predictive scores for recurrence and bleeding are not sufficiently reliable, and the safety and efficacy of reduced-dose anticoagulation remain unclear. In the future, precision and patient-centred medicine may improve treatment decisions in this area.

Duration of antibiotic therapy for multidrug resistant Pseudomonas aeruginosa pneumonia: is shorter truly better?

BACKGROUND: The 2016 IDSA guideline recommends a treatment duration of at least 7 days for hospital-acquired (HAP)/ventilator-associated pneumonia (VAP). The limited literature has demonstrated higher rates of recurrence for non-glucose fermenting gram-negative bacilli with short course therapy, raising the concern of optimal treatment duration for these pathogens. Therefore, we aimed to compare the outcomes for patients receiving shorter therapy treatment (≤ 8 days) versus longer regimen (> 8 days) for the treatment of multidrug resistant (MDR) Pseudomonas pneumonia. METHODS: A single-center, retrospective cohort study was conducted to evaluate adult patients receiving an antimicrobial regimen with activity against MDR Pseudomonas aeruginosa in respiratory culture between 2017 and 2020 for a minimum of 6 consecutive days. Exclusion criteria were inmates, those with polymicrobial pneumonia, community-acquired pneumonia, and infections requiring prolonged antibiotic therapy. RESULTS: Of 427 patients with MDR P. aeruginosa respiratory isolates, 85 patients were included. Baseline characteristics were similar among groups with a median age of 65.5 years and median APACHE 2 score of 20. Roughly 75% had ventilator-associated pneumonia. Compared to those who received ≤ 8 days of therapy, no difference was seen for clinical success in patients treated for more than 8 days (80% vs. 65.5%, p = 0.16). The number of 30-day and 90-day in-hospital mortality, 30-days relapse, and other secondary outcomes did not significantly differ among the treatment groups. CONCLUSIONS: Prolonging treatment duration beyond 8 days did not improve patient outcomes for MDR P. aeruginosa HAP/VAP.

The impact of immune recovery and treatment duration on disseminated histoplasmosis consolidation therapy in AIDS patients.

INTRODUCTION: The present study investigated the impact of immune recovery and the duration of antifungal adherence in the consolidation phase of disseminated histoplasmosis (DH) in acquired immune deficiency syndrome (AIDS) patients living in a hyperendemic area in northeastern Brazil. MATERIAL AND METHODS: Sixty-nine patients with DH/AIDS, admitted to the São José Hospital between 2010 and 2015, who continued histoplasmosis consolidation therapy at the outpatient clinic were studied. The follow-up duration was at least 24 months. RESULTS: Sixty-eight patients used itraconazole 200-400 mg/day or amphotericin B deoxycholate weekly during the consolidation phase, and six patients relapsed during follow-up. The overall median duration of consolidation antifungal use was 250 days [IQR 101 - 372]. Antifungal withdrawal by medical decision occurred in 41 patients (70.7 %) after a median of 293 days [IQR 128 - 372] of use; 16 patients discontinued by their own decision, with a median of 106 days [IQR 37 - 244] of therapy; three patients had no information available, and nine continued on AF therapy. The median CD4+ T-cell count in the group without relapse was 248 cells/µL [IQR 115-355] within 6 months after admission; conversely, in the relapse group, the median cell count remained below 100 cells/µL. Irregular adherence to highly active antiretroviral therapy (HAART) was the leading risk factor associated with relapse and death (p< 0.01). DISCUSSION: The regular use of HAART, combined with immune recovery, proved to be highly effective in preventing relapses in DH/AIDS patients, suggesting that long-term antifungal therapy may not be necessary.

Overall Survival, Treatment Duration, and Rechallenge Outcomes With ICI Therapy for Recurrent or Metastatic HNSCC.

Importance: Immune checkpoint inhibition (ICI) is a frontline treatment for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), but questions remain surrounding optimal duration of therapy, benefits and risks of ICI rechallenge, and efficacy in first vs subsequent lines of therapy. Objectives: To estimate survival in US patients receiving ICI-based treatment for R/M HNSCC, compare outcomes associated with treatment discontinuation vs continuation at 1 or 2 years, and assess outcomes after immunotherapy rechallenge. Design, Setting, and Participants: This retrospective, population-based cohort study included adult patients in the Flatiron Health nationwide oncology database treated with immunotherapy for R/M HNSCC from 2015 to 2023. Data cutoff was August 31, 2023; data analysis was conducted from December 2023 to February 2024. Exposures: Treatment continuation vs discontinuation at 1 and 2 years; rechallenge with ICI after at least a 60-day period off ICI therapy without intervening systemic treatment (immediate rechallenge), or with intervening systemic treatment (delayed rechallenge). Main Outcomes and Measures: Overall survival (OS) from ICI initiation was analyzed using the Kaplan-Meier method. Cox multivariable regression was used to examine associations of key variables (line of therapy, human papillomavirus [HPV] status, Eastern Cooperative Oncology Group [ECOG] performance status) with survival. Results: The cohort included 4549 patients with R/M HNSCC who received ICI-containing therapy (median [IQR] age, 66 [59-72] years; 3551 [78.1%] male; 56 [1.2%] Asian, 260 [5.7%] Black or African American, 3020 [66.4%] White, 1213 [26.7%] other or unknown race; 3226 [70.9%] ECOG performance status 0 or 1). There were 3000 patients (65.9%) who received ICI in frontline and 1207 (26.5%) in second line; 3478 patients (76.5%) received ICI monotherapy. Median (IQR) OS was 10.9 (4.1-29.1) months and was longer in patients who received ICI in frontline therapy (12.2 [4.8-32.0] vs 8.7 [3.2-22.4] months), had HPV-positive cancer (16.6 [6.5-43.9] vs 8.8 [3.5-24.0] months), and had ECOG performance status 0 or 1 (13.5 [5.2-33.9] vs 5.5 [2.0-13.7] months). There were no survival differences on adjusted analysis between patients who stopped vs those who continued ICI at 1 or 2 years. Median (IQR) OS after ICI rechallenge was 15.7 (13.7-21.9) months in the immediate rechallenge group and 9.9 (3.7-18.1) months in the delayed rechallenge group. Conclusions and Relevance: In this large cohort study of patients with R/M HNSCC receiving ICI-based therapy, survival estimates closely mirrored clinical trial results, both in frontline and later-line settings. Discontinuation of ICI in long-term responders at 1 or 2 years may be a reasonable strategy that does not appear to compromise survival. ICI rechallenge was associated with clinical benefit in a subset of patients.

Therapy duration and improvement of ventricular function in de novo heart failure: the Heart Failure Optimization study.

BACKGROUND AND AIMS: In patients with de novo heart failure with reduced ejection fraction (HFrEF), improvement of left ventricular ejection fraction (LVEF) is expected to occur when started on guideline-recommended medical therapy. However, improvement may not be completed within 90 days. METHODS: Patients with HFrEF and LVEF ≤ 35% prescribed a wearable cardioverter-defibrillator between 2017 and 2022 from 68 sites were enrolled, starting with a registry phase for 3 months and followed by a study phase up to 1 year. The primary endpoints were LVEF improvement > 35% between Days 90 and 180 following guideline-recommended medical therapy initiation and the percentage of target dose reached at Days 90 and 180. RESULTS: A total of 598 patients with de novo HFrEF [59 years (interquartile range 51-68), 27% female] entered the study phase. During the first 180 days, a significant increase in dosage of beta-blockers, renin-angiotensin system inhibitors, and mineralocorticoid receptor antagonists was observed (P < .001). At Day 90, 46% [95% confidence interval (CI) 41%-50%] of study phase patients had LVEF improvement > 35%; 46% (95% CI 40%-52%) of those with persistently low LVEF at Day 90 had LVEF improvement > 35% by Day 180, increasing the total rate of improvement > 35% to 68% (95% CI 63%-72%). In 392 patients followed for 360 days, improvement > 35% was observed in 77% (95% CI 72%-81%) of the patients. Until Day 90, sustained ventricular tachyarrhythmias were observed in 24 wearable cardioverter-defibrillator carriers (1.8%). After 90 days, no sustained ventricular tachyarrhythmia occurred in wearable cardioverter-defibrillator carriers. CONCLUSIONS: Continuous optimization of guideline-recommended medical therapy for at least 180 days in HFrEF is associated with additional LVEF improvement > 35%, allowing for better decision-making regarding preventive implantable cardioverter-defibrillator therapy.

Use of Fever Duration to Guide Management of Urinary Tract Infection.

BACKGROUND: The appropriate duration of antimicrobial therapy for febrile urinary tract infection (fUTI) in children has not been established. This study examined the optimal duration of treatment for fUTI in children. METHODS: We created a protocol that used fever duration to determine the duration of antibiotic administration. Transvenous antibiotics were administered until 3 days after resolution of fever, followed by oral antibiotics for 1 week. Diagnosis of fUTI was based on a fever of 37.5°C or higher and a quantitative culture of catheterized urine yielded a bacteria count of ≥5 × 104. Acute focal bacterial nephritis (AFBN) and pyelonephritis (PN) were diagnosed on the basis of contrast-enhanced computed tomography (eCT) findings. We retrospectively reviewed treatment outcomes. RESULTS: Of the 78 patients treated according to our protocol, data from 58 were analyzed-49 children (30 boys) had PN and nine (three boys) had AFBN. Blood test results showed that patients with AFBN had significantly higher white blood cell counts and C-reactive protein levels than did those with PN; however, urinary findings and causative bacteria did not differ between groups. Time to resolution of fever and duration of intravenous antibiotic administration were significantly longer in patients with AFBN than in those with PN. However, average duration of AFBN treatment was 14.2 days, which was shorter than the previously reported administration period of 3 weeks. No recurrence was observed in AFBN patients. CONCLUSIONS: A protocol that used fever duration to determine the duration of antimicrobial treatment was useful. Invasive examinations, such as eCT, were not required.

Identifying excessive length of antibiotic treatment duration for hospital-acquired infections: a semi-automated approach to support antimicrobial stewardship.

BACKGROUND: Avoiding excessive antibiotic treatment duration is a fundamental goal in antimicrobial stewardship. Manual collection of data is a time-consuming process, but a semi-automated approach for data extraction has been shown feasible for community-acquired infections (CAI). Extraction of data however may be more challenging in hospital-acquired infections (HAI). The aim of this study is to explore whether semi-automated data extraction of treatment duration is also feasible and accurate for HAI. METHODS: Data from a university-affiliated hospital over the period 1-6-2020 until 1-6-2022 was used for this study. From the Electronic Health Record, raw data on prescriptions, registered indications and admissions was extracted and processed to define treatment courses. In addition, clinical notes including prescription instructions were obtained for the purpose of validation. The derived treatment course was compared to the registered indication and the actual length of treatment (LOT) in the clinical notes in a random sample of 5.7% of treatment courses, to assess the accuracy of the data for both CAI and HAI. RESULTS: Included were 10.564 treatment courses of which 73.1% were CAI and 26.8% HAI. The registered indication matched the diagnosis as recorded in the clinical notes in 79% of treatment courses (79.2% CAI, 78.5% HAI). Higher error rates were seen in urinary tract infections (UTIs) (29.0%) and respiratory tract infections (RTIs) (20.5%) compared to intra-abdominal infections (7.4%), or skin or soft tissue infections (11.1%), mainly due to incorrect specification of the type of UTI or RTI. The LOT was accurately extracted in 98.5% of courses (CAI 98.2%, HAI 99.3%) when compared to prescriptions in the EHR. In 21% of cases however the LOT did not match with the clinical notes, mainly if patients received treatment from other health care providers preceding or following the present course. CONCLUSION: Semi-automatic data extraction can yield reliable information about the indication and LOT in treatment courses of hospitalized patients, for both HAI and CAI. This can provide stewardship programs with a surveillance tool for all in-hospital treated infections, which can be used to achieve stewardship goals.

Evaluation of the Treatment Duration of Japanese Patients With Pancreatic Cancer in a Real-World Setting Using a Large Hospital Claims Database: The SUISEI Study.

OBJECTIVES: To clarify the treatment reality of pancreatic cancer in Japan, focusing on treatment duration and time to death. MATERIALS AND METHODS: We retrospectively analyzed Japanese hospital claims data for patients diagnosed with pancreatic cancer between April 2009 and October 2018 to investigate treatment patterns, duration of first-line chemotherapy, and time to death. RESULTS: Of 81,185 eligible patients, 54.2% were male, the mean age was 71.7 years, and 23.3% (n = 18,884) received chemotherapy as primary treatment. The median treatment duration was 14.1 weeks for the 6.7% of patients who received oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX; recommended first-line regimen) and 16.9 weeks for the 30.2% of patients who received gemcitabine plus nab-paclitaxel (GEM + nab-PTX). Time to death for patients who received FOLFIRINOX or GEM + nab-PTX was similar (15.4 and 14.8 months, respectively). The duration of first-line chemotherapy regimens tended to increase annually for both regimens. The time to death for all first-line chemotherapy regimens also increased annually. CONCLUSIONS: This study revealed the treatment reality of pancreatic cancer in the real-world Japanese setting. Treatment duration and time to death tended to increase over time and did not differ numerically between FOLFIRINOX and GEM + nab-PTX.

Association between duration of antidepressant treatment for major depressive disorder and relapse rate after discontinuation: A meta-analysis.

The optimal duration of antidepressant treatment for patients with major depressive disorder to reduce the risk of relapse after discontinuation remains uncertain. Medline, Cochrane Central Register of Controlled Trials, and Embase were systematically searched for randomized controlled trials (RCTs) with a discontinuation design. A single-group summary meta-analysis was performed to calculate 6-month relapse rates after discontinuation. Meta-regression with restricted cubic splines was performed to model the non-linear relationship between treatment duration and relapse rate after discontinuation. Thirty-five RCTs were included. The relapse rate after discontinuation was approximately 34.81 % at 6 months and 45.12 % at 12 months. After controlling for covariates, the meta-analysis shows that the duration of treatment is associated with the risk of relapse after discontinuation in a non-linear curve, with a relatively higher risk of relapse observed for a duration of less than three months. There appears to be no further reduction in the risk of relapse when treatment is continued for over six months. Our results indicate the importance of at least three months of treatment to avoid the relatively high risk of relapse after discontinuation. The additional benefit of longer treatment remains to be proven.

Dynamic Risk Model for the Medical Treatment of Graves' Hyperthyroidism according to Treatment Duration.

BACKGRUOUND: Changes in thyrotropin receptor antibody (TRAb) levels are associated with the clinical outcomes of Graves' hyperthyroidism. However, the effects of the patterns of TRAb changes on patient prognosis according to the treatment duration of antithyroid drugs (ATDs) are not well established. METHODS: In this retrospective cohort study, 1,235 patients with Graves' hyperthyroidism who were treated with ATDs for more than 12 months were included. Patients were divided into two groups according to treatment duration: group 1 (12-24 months) and group 2 (>24 months). Risk prediction models comprising age, sex, and either TRAb levels at ATD withdrawal (model A) or patterns of TRAb changes (model B) were compared. RESULTS: The median treatment duration in groups 1 (n=667, 54%) and 2 (n=568, 46%) was 17.3 and 37.1 months, respectively. The recurrence rate was significantly higher in group 2 (47.9%) than in group 1 (41.4%, P=0.025). Group 2 had significantly more goiter, thyroid eye disease, and fluctuating and smoldering type of TRAb pattern compared with group 1 (all P<0.001). The patterns of TRAb changes were an independent risk factor for recurrence after adjusting for other confounding factors in all patients, except in group 1. Integrated discrimination improvement and net reclassification improvement analyses showed that model B performed better than model A in all patients, except in group 1. CONCLUSION: The dynamic risk model, including the patterns of TRAb changes, was more suitable for predicting prognosis in patients with Graves' hyperthyroidism who underwent longer ATD treatment duration.

Short versus prolonged duration of therapy for Pseudomonas aeruginosa bacteraemia: a systematic review and meta-analysis.

The optimal duration of therapy for Pseudomonas aeruginosa bloodstream infection (PSA-BSI) is unknown, with prolonged therapy frequently favored due to severity of infection, patient complexity, risk of multi-drug resistance, and high mortality. We therefore conducted a systematic review and meta-analysis of studies with head-to-head comparison of short versus prolonged therapy for PSA-BSI. A comprehensive search including Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus was performed. We pooled risk ratios using DerSimonian-Laird random effects model and performed subgroup analysis of outcomes including all-cause mortality, recurrent infection, and composite of these outcomes among patients receiving short versus prolonged therapy for PSA-BSI. Heterogeneity was assessed by the I2-index. Risk of bias for cohort studies was assessed using ROBINS-I tool. Of the 908 identified studies, six were included in the systematic review and five studies with head-to-head comparison of treatment duration were assessed in the meta-analysis, totalling 1746 patients. No significant difference in propensity score-weighted composite outcome (30-day all-cause mortality or recurrent infection) was noted between patients receiving short or prolonged therapy, with a pooled RR risk ratio of 0.80 (95% CI confidence interval 0.51-1.25, P=0.32; I2 = 0%). Additionally, duration of therapy did not impact individual outcomes of 30-day all-cause mortality or recurrent/persistent infection. Our meta-analysis demonstrated that short duration of antimicrobial therapy may have similar efficacy to prolonged treatment for PSA-BSI. Future randomized trials will be necessary to definitively determine optimal management of PSA bacteraemia.

Duration of orthodontic treatment with clear aligners versus fixed appliances in crowding cases: a systematic review.

OBJECTIVE: To critically appraise and assess the currently observed evidence about the difference in orthodontic treatment duration between clear aligners and fixed appliances in crowding cases. MATERIALS AND METHODS: An electronic search without limitations was conducted from inception to June 2023 covering nine databases: The Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Scopus, Web of Science, Google Scholar, Trip, CINAHL via EBSCO, EMBASE via OVID and ProQuest. Randomized controlled trials (RCTs) and matched non-randomized studies were included in this systematic review. Risk of Bias was assessed via Cochrane's tool (RoB 2) for RCTs and ROBINS-I tool for non-randomized studies. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework was employed to evaluate the overall quality of evidence. RESULTS: Out of the 3537 articles initially identified, ten eligible studies were included in this systematic review; six were RCTs. Only one study offered extraction-based treatment, while the other nine adopted non-extraction treatments. According to the GRADE, there is low evidence that treatment duration in mild to moderate crowding cases with clear aligners is similar to that in fixed orthodontic appliances. Meta-analysis was not administered due to high inconsistency. CONCLUSIONS: Based on currently available information, there was no significant difference in the treatment duration between the CA and FA groups in mild to moderate crowding cases. Further well-performed RCTs, especially in severe cases, are required. CLINICAL RELEVANCE: Time efficiency is an essential outcome measure for clinical orthodontic practice. While the type of appliance used is a critical determinant of treatment duration, orthodontists should be aware of other factors that can significantly impact treatment time, such as patient and treatment-related factors.

Clinical outcomes of narrow- and regular-diameter implants with bone augmentation in the anterior maxilla: a systematic review and meta-analysis.

OBJECTIVES: To evaluate the clinical outcomes of narrow-diameter implants (NDIs) and regular-diameter implants (RDIs) with bone augmentation in the anterior maxilla, with implant survival rate (ISR) as the primary outcome. Additionally, secondary outcomes such as peri-implant marginal bone loss (MBL), pocket probing depth (PPD), mechanical complications, and biological complications were also considered. MATERIALS AND METHODS: A thorough literature search was performed to identify randomized controlled trials and cohort studies comparing outcomes of NDIs and RDIs with bone augmentation in the anterior maxilla published up to February 2024. Only studies with a minimum follow-up period of 12 months were selected for analysis. Meta-analysis was performed if at least two articles with similar characteristics were available. RESULTS: Of the 288 articles initially considered, 5 were included in the analysis, involving 282 NDIs and 100 RDIs. At the 36-month follow-up, no statistically significant differences in ISR, which ranged 93.8-100% for NDIs and were 100% for RDIs, were observed between the two groups (relative risk, 0.989; 95% confidence interval, 0.839-1.165; p = 0.896). Similarly, MBL and PPD did not differ significantly between the two groups. Soft tissue dehiscence was the most common complication found in RDIs. CONCLUSION: The results indicate that NDIs yield clinical outcomes similar to those of RDIs with bone augmentation in the anterior maxilla over a 36-month follow-up period. CLINICAL RELEVANCE: Considering the similar clinical outcomes, the shortened treatment duration and more rapid esthetic improvement associated with NDIs may render them preferrable to RDIs with bone augmentation, particularly in this esthetic zone.