Optimizing Fluid Management Guided by Volumetric Parameters in Patients with Sepsis and ARDS.

We compared two de-escalation strategies guided by either extravascular lung water or global end-diastolic volume-oriented algorithms in patients with sepsis and ARDS. Sixty patients with sepsis and ARDS were randomized to receive de-escalation fluid therapy, guided either by the extravascular lung water index (EVLWI, n = 30) or the global end-diastolic volume index (GEDVI, n = 30). In cases of GEDVI > 650 mL/m2 or EVLWI > 10 mL/kg, diuretics and/or controlled ultrafiltration were administered to achieve the cumulative 48-h fluid balance in the range of 0 to -3000 mL. During 48 h of goal-directed de-escalation therapy, we observed a decrease in the SOFA score (p < 0.05). Extravascular lung water decreased only in the EVLWI-oriented group (p < 0.001). In parallel, PaO2/FiO2 increased by 30% in the EVLWI group and by 15% in the GEDVI group (p < 0.05). The patients with direct ARDS demonstrated better responses to dehydration therapy concerning arterial oxygenation and lung fluid balance. In sepsis-induced ARDS, both fluid management strategies, based either on GEDVI or EVLWI, improved arterial oxygenation and attenuated organ dysfunction. The de-escalation therapy was more efficient for direct ARDS.

Sometimes it is better to just make it simple. De-escalation of oncoplastic and reconstructive procedures.

Simple breast conservation surgery (sBCS) has technically advanced onto oncoplastic breast procedures (OBP) to avoid mastectomy and improve breast cancer patients' psychosocial well-being and cosmetic outcome. Although OBP are time-consuming and expensive, we are witnessing an increase in their use, even for cases that could be managed with sBCS. The choice between keeping it simple or opting for more complex oncoplastic procedures is difficult. This review proposes a pragmatic approach in assisting this decision. Medical literature suggests that OBP and sBCS might be similar regarding local recurrence and overall survival, and patients seem to have higher satisfaction levels with the aesthetic outcome of OBP when compared to sBCS. However, the lack of comprehensive high-quality research assessing their safety, efficacy, and patient-reported outcomes hinders these supposed conclusions. Postoperative complications after OBP may delay the initiation of adjuvant RT. In addition, precise displacement of the breast volume is not effectively recorded despite surgical clips placement, making accurate dose delivery tricky for radiation oncologists, and WBRT preferable to APBI in complex OBP cases. With a critical eye on financial toxicity, patient satisfaction, and oncological outcomes, OBP must be carefully integrated into clinical practice. The thoughtful provision of informed consent is essential for decision-making between sBCS and OBP. As we look into the future, machine learning and artificial intelligence can potentially help patients and doctors avoid postoperative regrets by setting realistic aesthetic expectations.

Molecular Pathways of Breast Cancer in Systemic Sclerosis: Exploratory Immunohistochemical Analysis from the Sclero-Breast Study.

Several authors reported an increased risk of cancer in SSc patients, including breast cancer (BC). Nevertheless, the mechanisms underlying this association have not yet been clarified. SSc and BC share several molecular pathways, which seem to play a common etiopathogenetic role. The previously published Sclero-Breast study demonstrated the development of BC with a good prognosis among these patients, which could be explained by an autoimmune background as a possible mechanism for limiting tumor extension. Here, we report the results of an IHC analysis of molecular pathways known to be common drivers for both diseases, with the aim to better define the mechanisms underlying a good prognosis of BC in patients affected by SSc. The analysis demonstrated higher TILs rates in all BC subgroups, with a high rate of PD-L1 expression especially in TNBC and HER2-positive BC, suggesting a less aggressive behavior in these patients compared to the general population. These results support a possible de-escalation strategy of cancer therapies in these fragile patients. These data could represent a starting point for future prospective studies based on the clinical application of these biomarkers with a larger sample size to promote a personalized and targeted oncological treatment for this specific subset of patients.

Quality of Life Analysis of HPV-Positive Oropharyngeal Cancer Patients in a Randomized Trial of Reduced-Dose Versus Standard Chemoradiotherapy: 5-Year Follow-Up.

Background: Human papillomavirus-positive oropharyngeal carcinoma (HPVOPC) portends a more favorable prognosis compared to environmentally related oropharynx cancer (EROPC). Patients with HPVOPC may be overtreated and endure unnecessary long-term toxicities. Methods: Patients with untreated locally advanced HPVOPC received induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (TPF) and were randomized to standard chemoradiotherapy (sdCRT) (70 Gy) or reduced-dose chemoradiotherapy (rdCRT) (56 Gy) with weekly carboplatin. Patients were followed for changes in five validated quality of life (QoL) surveys: MD Anderson Dysphagia Inventory and Symptom Inventory for head and neck cancer (MDADI, MDASI-HN), Xerostomia Questionnaire (XQ), and European Organization for Research and Treatment of Cancer Questionnaire (EORTC) with head and neck module (EORTC HN). The secondary endpoints of this study were 5-year progression-free survival (PFS) and overall survival (OS). Results: Twenty patients were enrolled and randomized to rdCRT (n = 12) or sdCRT (n = 8). Median follow-up was 88 months. At 5 years, difference in QoL changes all favored the rdCRT arm and two QoL scales reached statistical significance (EORTC global health score: 11.49 vs. -23.94, P = 0.014; EORTC symptom scale: -7.76 vs. 15.19, P = 0.015). The 5-year PFS and OS were 87.5% and 83.3% for sdCRT and rdCRT, respectively. Conclusions: Therefore, rdCRT after TPF in HPVOPC is feasible in accordance with the earlier results of the Quarterback Trial and long-term follow-up. These limited results are more favorable in specific QoL domains compared to those of sdCRT and demonstrate equivalent long-term survival. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT01706939, The Quarterback Trial [NCT01706939].

Extended, standard, or De-escalation antiplatelet therapy for patients with coronary artery disease undergoing percutaneous coronary intervention? A trial-sequential, bivariate, influential, and network meta-analysis.

AIMS: The relative safety and efficacy of de-escalation, extended duration (ED) (>12-months), and standard dual antiplatelet therapy for 12-months (DAPT-12) in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) remains controversial. METHODS AND RESULTS: Online databases were queried to identify relevant randomized control trials (RCTs). ED-DAPT, high-potency (HP) DAPT, shorter duration (SD) DAPT, and low-dose (LD) DAPT were compared with DAPT-12. A trial sequential, bivariate, influential, and frequentist network meta-analysis (NMA) was performed to determine the pooled estimates. A total of 30 RCTs comprising 81 208 (40 839 experimental, 40 369 control arm) patients with CAD were included in the quantitative analysis. On NMA, compared with DAPT-12, all types of de-escalation, HP-DAPT-12, and ED-DAPT strategies had a statistically non-significant difference in the incidence of MACE at a median follow-up of 1-year. Similarly, there was no significant difference in the incidence of stroke, stent thrombosis, target lesion revascularization (TLR), target vessel revascularization (TVR), and all-cause mortality between DAPT-12 and all other strategies. The network estimates showed a significantly lower incidence of major bleeding with DAPT for 3-months followed by P2Y12-inhibitor monotherapy (RR 0.62, 95% CI 0.45-0.84), while a higher risk of bleeding with HP-DAPT for 12 months (RR 1.55, 95% CI 1.16-2.06). The net clinical benefit and rankograms also favoured DAPT-3 (P2Y12) and discouraged the use of HP-DAPT-12 and ED-DAPT. A subgroup analysis of 19 RCTs restricted to patients who presented with acute coronary syndrome (ACS) mirrored the findings of pooled analysis. A sensitivity analysis revealed no influence of any individual study or individual strategy on net ischemic estimates. The trial sequential analysis (TSA) illustrated a consistently non-significant difference at the interim analysis of trials, reaching the futility area for MACE, while the cumulative Z-values line surpassed the monitoring boundary as well as the required information size for major bleeding favouring de-escalation strategy. CONCLUSION: DAPT for three months followed by ticagrelor-only and use of aspirin + clopidogrel after a short period of high potency DAPT appears to be a safe strategy for treating post-PCI patients. However, given the methodological limitations and inclusion of a small number of trials in novel de-escalation strategies, these findings need validation by future large scale RCTs.

Sustained Improvements in Antimicrobial Therapy and Clinical Outcomes following a Pharmacist-Led Antimicrobial Stewardship Intervention: Uncontrolled Before-After Study.

Our antimicrobial pharmacist-led intervention included: (a) a structured review of antibiotic prescriptions; (b) educating prescribers on antimicrobial therapy; (c) monthly reporting of department-level rates of blood sampling for culture. Daily review began in May 2018 and was discontinued after 10 months; however, the other interventions were conducted throughout the study period. This study aimed to evaluate the sustained impact of pharmacist's interventions on antimicrobial therapy and clinical outcomes between the baseline (May-December 2017), intervention (May-December 2018), and post-intervention (May-December 2019) periods. The rate of blood culture collections before starting antipseudomonal agent therapy was significantly increased from the baseline to post-intervention periods (71% vs. 85%, p < 0.001). Antipseudomonal agent therapy was more frequently de-escalated in the post-intervention period than in the baseline period (73% vs. 54%, p = 0.038). Total use of antipseudomonal agents was reduced from the baseline to intervention periods and persisted during the post-intervention period (50.5 vs. 41.8 and 42.6 DDD per 1000 patient-days, p = 0.016 and p = 0.022, respectively). During the study period, there were significant reductions in the incidence of hospital-acquired Clostridioides difficile infection (1.12, 0.54, and 0.51 per 10,000 patient-days, respectively, p = 0.031) and 30-day mortality with bacteremia (19%, 18%, and 12%, respectively, p = 0.005). Our pharmacist-led interventions sustainably achieved appropriate antimicrobial therapy and improved clinical outcomes.

Abatement of potent P2Y12 antagonist-based dual antiplatelet therapy after coronary intervention: A network meta-analysis of randomized controlled trials.

Introduction: Dual antiplatelet therapy (DAPT) including prasugrel or ticagrelor is recommended in patients with acute coronary syndromes (ACS) treated with coronary intervention (PCI). Acknowledging the importance of bleeding, multiple trials tested abatement schemes including uniform or guided de-escalation from the potent P2Y12 inhibitor (P2Y12-De) or P2Y12 inhibitor monotherapy (P2Y12-Mo) with heterogeneous results. We aimed to perform a systematic review and network meta-analysis of the impact of DAPT abatement strategies in patients with PCI. Methods: Electronic databases were searched for relevant randomized clinical studies evaluating clinical outcomes of patients after PCI. The rate of adverse events was evaluated using a frequentist network metanalysis. The random-effects model was used to combine risk estimates across trials and risk ratio (RR) with 95% confidence intervals (95% CIs) served as summary statistics. The primary endpoints of interest were the rate of major cardiac adverse events (MACE, defined as the composite of cardiovascular mortality, myocardial infarction and stroke) and bleeding. Results: Ten studies were identified randomizing 42511 patients. 6359 switched to the P2Y12-De and 13062 switched to the P2Y12-Mo. The risk of MACE, reflected a 24% reduction in the P2Y12-De and a 14% in the P2Y12-Mo in comparison with the DAPT strategy using potent P2Y12 inhibitors (RR: 0.76 [0.62, 0.94], and RR: 0.86 [0.75, 0.99], p < 0.05 both). A 35% risk reduction of major bleeding was seen with monotherapy (RR: 0.65 [0.46, 0.91],) contrasting the de-escalation trials where this effect was not significant (RR: 0.84 [0.57, 1.22]). All bleeding and minor bleeding events were reduced with both strategies. Indirect P2Y12-Mo versus P2Y12-De comparisons exhibited them as similar alternatives without significant differences. Conclusion: Our analysis suggests that both P2Y12-De and P2Y12-Mo reduce ischemic events and bleeding among PCI-treated ACS patients. Ischemic benefit was more expressed with P2Y12-De, however, reduction of major bleeding was only significant with P2Y12-Mo strategy. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021258502, identifier CRD42021258502.

A Food and Drug Administration analysis of survival outcomes comparing the Adjuvant Paclitaxel and Trastuzumab trial with an external control from historical clinical trials.

BACKGROUND: Although the Adjuvant Paclitaxel and Trastuzumab (APT) trial has been adopted clinically, single-arm trials have limitations, and interest remains whether these patients with small node-negative human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC) would benefit from more intensive chemotherapy. This analysis explored whether external controls can contextualize single-arm studies to add to clinical decision making in the use of de-escalated therapy in patients with low-risk HER2-positive EBC. PATIENTS AND METHODS: Patient-level data from five randomized trials supporting drug approval in adjuvant HER2-positive EBC were pooled, and patients with low-risk EBC were selected (n = 1770). Patients treated concurrently with trastuzumab and either anthracycline/cyclophosphamide/taxane/trastuzumab (ACTH) or taxane/carboplatin/trastuzumab (TCH; n = 1366) were matched (1:1) to patients treated with paclitaxel and trastuzumab (TH) in the APT trial (n = 406) using propensity scores. Patients treated with anthracycline/cyclophosphamide/taxane (ACT; n = 374) were also matched (1:1) to those treated with TH. Propensity scores were estimated using covariates of age, tumor stage, estrogen receptor status, progesterone receptor status, and histological grade. RESULTS: After matching, the estimated probabilities of invasive disease-free survival (iDFS) at 3 and 5 years were 98.6% and 96.5% in the TH arm, and 96.6% and 92.9% in the ACTH/TCH arm, respectively. The estimated probabilities of overall survival (OS) at 3 and 5 years were 99.7% and 99.3% in the TH arm, and 99.0% and 97.4% in the ACTH/TCH arm, respectively. Comparing the TH arm with the ACT arm in the matched sample, the estimated difference in iDFS was 7.5% (TH 98.8% and ACT 91.3%) at 3 years and 12.6% (TH 96.1% and ACT 83.5%) at 5 years. The estimated difference in OS was 2.6% (TH 100% and ACT 97.4%) at 3 years, and 5.3% (TH 99.3% and ACT 94.0%) at 5 years. CONCLUSIONS: Our analyses suggest that patients' outcomes in both arms were in general similar, thus providing additional reassurance regarding de-escalation of therapy.

Emerging Concepts and Novel Strategies in Radiation Therapy for Laryngeal Cancer Management.

Laryngeal squamous cell carcinoma is the second most common head and neck cancer. Its pathogenesis is strongly associated with smoking. The management of this disease is challenging and mandates multidisciplinary care. Currently, accepted treatment modalities include surgery, radiation therapy, and chemotherapy-all focused on improving survival while preserving organ function. Despite changes in smoking patterns resulting in a declining incidence of laryngeal cancer, the overall outcomes for this disease have not improved in the recent past, likely due to changes in treatment patterns and treatment-related toxicities. Here, we review emerging concepts and novel strategies in the use of radiation therapy in the management of laryngeal squamous cell carcinoma that could improve the relationship between tumor control and normal tissue damage (therapeutic ratio).

[Diagnosis and Treatment Recommendation and Exploration for Critical and Refractory Adverse Effects Related to Immunocheckpoint Inhibitors].

The application of immunological checkpoint inhibitors (ICIs) has modified many treatment strategies of malignant tumors, which has become a milestone in cancer therapy. The principle of action can be explained as "brake theory". After releasing the brakes by ICIs, unprecedented systemic toxicities, even some refractory and fatal immune-related adverse effects (irAEs) may develop. In this article, we summarized the recommended treatments of grade 3-4 severe irAEs in the latest European Society for Medical Oncology (ESMO), National Comprehensive Cancer Network (NCCN)/American Society of Clinical Oncology (ASCO), Society for Immunotherapy of Cancer (SITC) and Chinese Society of Clinical Oncology (CSCO) guidelines and consensus. We also performed a systemic review of case reports and reviews of irAEs up to May 20, 2019 in PubMed and Chinese journals. Successful applications of specific immunosuppressive drugs and stimulating factors beyond the above guidelines and consensus were supplemented and highlighted, including agents blocking interleukin 6 (IL-6), rituximab, anti-tumor necrosis factor-α (TNFα) monoclonal antibody (mAb), anti-integrin 4 mAb, Janus kinase inhibitors, thrombopoietin receptor agonists and antithymocyte globulin (ATG) etc. We put some concerns of using high-dose steroids for long-term, and emphasize the secondary infections, tumor progression, and unavailability of ICI re-challenge during steroid treatment. We propose the "De-escalation Therapy" principle for severe and refractory irAEs, and suggest that immunosuppressive drugs specifically targeting cytokines should be used as early as possible. Many irAEs in the era of immunotherapy are unprecedented compared with traditional chemotherapy and small-molecule targeted therapy, which is a big challenge to oncologists. Therefore, the establishment of multidisciplinary system is very important for the management of cancer patients.

Antibiotic de-escalation therapy in patients with community-acquired nonbacteremic pneumococcal pneumonia.

Background De-escalation therapy is recommended as an effective antibiotic treatment strategy for several infectious diseases. While there is limited evidence supporting its clinical and cost-effective outcomes in patients with community-acquired bacteremic pneumonia, there is no evidence in patients with nonbacteremic pneumonia. Objective This study aimed to evaluate the antibiotic costs in patients who did and did not receive de-escalation therapy, based on the 2017 Japanese guidelines for the management of community-acquired nonbacteremic pneumococcal pneumonia of the Japanese Respiratory Society (JRS). Setting Kobe university hospital, Japan. Methods A retrospective case series review including antibiotic use and length of hospital stay was conducted using the medical records from April 2008 to May 2019 at a university hospital in Japan. Main outcome measure Impact of antibiotic de-escalation therapy on the antibiotic costs. Results Among 55 patients who were eligible, the treating physicians de-escalated antibiotics in 28 (51%). The differences in the median length of hospital stay and the incidence of adverse drug reactions between the two groups were not statistically significant (p = 0.67 and 1.0, respectively). However, the median total antibiotic cost per infected patient in the de-escalated group was significantly lower than that in the non-de-escalated group [$269.8 ($195-$389) vs. $420.5 ($221-$799), p = 0.048]. Conclusion Antibiotic de-escalation based on the 2017 JRS guidelines leads to a reduction in total antibiotic costs for the management of community-acquired nonbacteremic pneumococcal pneumonia.

Antifungal stewardship with an emphasis on candidaemia.

Antimicrobial resistance is a global threat. To counter the growing menace of antibiotic resistance, several stewardship initiatives have been incorporated as part of the overarching strategy of healthcare delivery. In contrast, antifungal stewardship (AFS) has attracted less attention for several reasons, such as limited antifungal resistance and the lesser burden of fungal infections compared with bacterial infections. However, the emergence of resistant fungi, such as multidrug-resistant Candida auris, has provided impetus to AFS programmes. This review summarises existing data on AFS programmes, particularly in relation to invasive candidiasis, both in the empirical setting and in the setting of proven infection.

Phase III study with FOLFIRI + cetuximab versus FOLFIRI + cetuximab followed by cetuximab alone in RAS and BRAF WT mCRC.

The optimal duration and intensity of first-line therapy in metastatic colorectal cancer patients once they have achieved an objective response is controversial. In a molecularly selected RAS and BRAF wild-type (wt) population, this concern is amplified. Once disease control has been achieved with a combination therapy including an anti-EGFR antibody, further exposure both to cytotoxic drugs and targeted therapy might result only in increased toxicity. In unresectable metastatic RAS and BRAF wt colorectal cancer patients, a deintensified therapy could represent a valuable option that might preserve quality of life. We designed a study to compare FOLFIRI/cetuximab to FOLFIRI/cetuximab for eight cycles followed by cetuximab alone in first-line treatment of RAS and BRAF (wt) metastatic colorectal cancer patients.

Antibiotic de-escalation principle in elderly patients with chronic obstructive pulmonary disease complicated with severe pneumonia.

The present study investigated the clinical effect of antibiotic de-escalation therapy in elderly patients with chronic obstructive pulmonary disease (COPD) complicated with severe pneumonia. According to the parity method of hospitalization number, 86 cases were selected and divided into the observation and control group with 43 cases each. Based on empirical antibiotic application, levofloxacin and cephalosporin antibiotics were used in the control group. After treatment for 3 days, the regimen was adjusted to antibiotics active against Gram-positive (G+) and Gram-negative (G-) bacteria such as the third or fourth generation cephalosporin antibiotics, combined with aminoglycoside, or macrolide antibiotics according to their effects. The treatment effects were re-evaluated after 3-7 days. Finally, broad-spectrum antibiotics such as imipenem were chosen or adjusted by bacterial cultures and drug sensitivity results in the control group. Patients in the observation group were treated according to the principle of antibiotic de-escalation therapy. Antibiotics active against G+ and G- bacteria were chosen as the first round of medication. After 3 days, broad-spectrum antibiotics such as imipenem were added to the treatment regimen. After 7 days, the treatment was changed to narrow spectrum antibiotic administration if the disease was in remission, and the antibiotic regimen was adjusted based on bacterial culture and drug sensitivity results. The treatment results were compared. The mechanical ventilation rate, antibiotic courses, number of antibiotics used, and mortality of the observation group were significantly lower than those in the control group (P<0.05). After treatment, lung function improved, partial pressure of oxygen and blood oxygen saturation increased, and partial pressure of carbon dioxide decreased in both groups. The improvement of all of the above parameters were more significant in the observation group (P<0.05). After treatment, the ratio of neutrophils over white blood cells and C-reactive protein levels of the two groups decreased, respiratory failure index (RFI) increased, and the changes were significantly more pronounced in the observation group (P<0.05). In conclusion, following the antibiotic de-escalation principle to treat older patients with COPD complicated with severe pneumonia can reduce the number of antibiotics required, improve lung function and clinical effects, and is safe and effective.

Is de-escalation of antimicrobials effective? A systematic review and meta-analysis.

BACKGROUND: De-escalation therapy is a strategy used widely to treat infections while avoiding the use of broad-spectrum antimicrobials. However, there is a paucity of clinical evidence to demonstrate the effectiveness and safety of de-escalation therapy compared to conventional therapy. METHODS: A systematic review and meta-analysis was conducted on de-escalation therapy for a variety of infections. A search of the MEDLINE (via PubMed), EMBASE, and Cochrane Library databases up to July 2015 for relevant studies was performed. The primary outcome was relevant mortality, such as 30-day mortality and in-hospital mortality. A meta-analysis was to be conducted for the pooled odds ratio using the random-effects model when possible. Both randomized controlled trials and observational studies were included in the analysis. RESULTS: A total of 23 studies were included in the analysis. There was no difference in mortality for most infections, and some studies favored de-escalation over non-de-escalation for better survival. The quality of most studies included was not high. CONCLUSIONS: This review and analysis suggests that de-escalation therapy is safe and effective for most infections, although higher quality studies are needed in the future.

Treatment de-escalation after mitoxantrone therapy: results of a phase IV, multicentre, open-label, randomized study of subcutaneous interferon beta-1a in patients with relapsing multiple sclerosis.

OBJECTIVE: The objective of this study was to assess the effect of treatment with interferon (IFN) ß-1a, 44 µg subcutaneously (sc) three times weekly (tiw), on clinical and magnetic resonance imaging (MRI) outcomes in patients with relapsing multiple sclerosis (MS) following mitoxantrone therapy. METHODS: This was an open-label, randomized, multicentre, rater-blinded, 96-week observational study conducted in Germany. Clinically stable patients with relapsing forms of MS, who had discontinued mitoxantrone treatment 1-6 months before study entry, were randomized to IFN ß-1a sc 44 µg tiw, or no treatment. The primary endpoint was time to first relapse. Secondary endpoints included the number of relapse-free patients, disease activity assessed by MRI and time to 3-month confirmed Expanded Disability Status Scale (EDSS) progression, all at week 96. RESULTS: A total of 30 patients were randomized (intent-to-treat population: 14 IFN ß-1a, 15 untreated; one patient from the safety population discontinued the study after 25 days owing to an adverse event and without providing any postbaseline efficacy data, and was thus excluded from the intent-to-treat population). Overall, 71.4% (10/14) of patients in the IFN ß-1a group remained relapse free over 96 weeks, versus 46.7% (7/15) in the untreated group (p = 0.26). IFN ß-1a delayed the time to first relapse versus no treatment (p = 0.14); time to first relapse (25th percentile) was 95.4 (IFN ß-1a) versus 46.0 weeks (no treatment). Confirmed EDSS progression was observed in five patients in each treatment group. Mean change in EDSS score was 0.3 in both groups (p = 0.79). Changes in the number or volume of T1 and T2 lesions at week 96 were not significantly different between treatment groups (p > 0.05). There were no new or unexpected adverse events related to IFN ß-1a treatment. CONCLUSIONS: Several endpoints appeared to show a benefit of IFN ß-1a treatment, but no significant differences could be detected owing to the small sample. Therefore, these data only permit, at best, tentative conclusions about the disease course in patients with MS after de-escalation from mitoxantrone and continuation with or without IFN ß-1a. Larger confirmatory studies are required.