Early Switch Research Articles

Раннее переключение с антивазопролиферативной терапии на имплант дексаметазона у пациентов при диабетическом макулярном отеке

Diabetic retinopathy (DR) is the one of severe complications of diabetes, associated with macular edema (DME), which is the main course of visual acuity loss in diabetic patients. The main pathological factors in diabetic retinopathy and diabetic macular edema (DME) are the inflammation and increasing of vascular endothelium growth factor activity (VEGF). The treatment of DME remains challenging during the times. We know that not all eyes respond optimally to anti-VEGF therapy. No clinical effect or minimal one among patients with persistent DME has led to an urgent need to develop new treatment protocols for this group of patients. In this case adding intravitreal corticosteroids to the treatment regimen is the most effective and predictаble than continued anti-VEGF therapy alone. According to results of randomized trials the functional and anatomical outcomes in eyes with refractory DME, which were switched to DEX implant had shown statistically significant better outcome, compared to anti-VEGF therapy alone. Another important question is efficiency and safety of using intravitreal corticosteroids as the first-line therapy in patients with DME. These new findings can help to define better the role of early switch to DEX implant in the current treatment algorithm of eyes with refractory DME. And find the optimal protocol of treatment patients with DME, determine the predictors of switching from anti-VEGF therapy to steroid intravitreal injections, in DME should be on the agenda of the future studies. Key words: anti-VEGF, DME, early switch, implant dexamethasone.

Cotrimoxazole and clindamycin in skin and soft tissue infections.

The aim of this study was to present recent microbiological, experimental, clinical and tolerance data for cotrimoxazole and clindamycin in the specific field of skin and soft tissue infections (SSTIs). Staphylococcus aureus and streptococci remain the leading cause of SSTIs. Cotrimoxazole is a good anti-Gram-positive agent with preserved activity against methicillin-susceptible and methicillin-resistant S. aureus (MRSA) and streptococci. Although clindamycin has good methicillin-susceptible S. aureus activity, a growing number of resistant MRSA and streptococci have been reported. Strong experimental data support the antitoxin activity of clindamycin, but clinical observations remain scarce. Several recent randomized trials involving cotrimoxazole and/or clindamycin demonstrate the efficacy and tolerance of both drugs. The oral formulation of both drugs may facilitate the implementation of early switch and early discharge protocols in clinical practice. Recent publications demonstrate that cotrimoxazole and clindamycin remain reliable and realistic therapeutic approaches for SSTIs.

Evaluation of early antibiotic switch therapy and its implications in general medical wards PPUKM

Background: Appropriate antibiotic usage in treating infection for hospitalized patient is important due to its impact on patient's health, cost involved as well as duration of hospitalization. The aim of this study was to evaluate current practice of early antibiotic switch therapy and its implication on treatment cost (antibiotic cost) and length of hospital stay Methods and materials: A prospective observational study was conducted involving 203 patients in PPUKM general medical wards from April 2019 to September 2019. Adult patient on intravenous antibiotic therapy for at least 48 h with infection suitable for early switching therapy were enrolled in this study. Eligible criteria = criteria for early switch to oral therapy were as follows:(i)Afebrile >24 h (T < 38’c)(ii)Able to tolerate orally or oral feeding (with no diarrhea & vomiting)(iii)Not more than 1 sepsis criteria present:(a)Heart rate >100,(b)Respiratoryrate > 20,(c)Systolic BP < 90,(d)WCC <4 or >12 (or in decreasing trend) # patient who fulfilled all these criteria are considered eligible for early IV to oral switch of antibiotics. Results: The prevalence of early intravenous to oral switch (IVOS) is 29.6% (n = 60). There was a statistically significant difference between the antibiotic costs in patients subjected to early IVOS (Mean MYR 122.8 ± 52.05) as compared to those given prolonged IV antibiotic therapy, (Mean MYR 202.9 ± 107.86); t(197) = 7.13, p < 0.001. Patients subjected to early IVOS had a significant reduction in length of hospital stay (Med = 3.0 days, IQR = 1.00) as compared to those who had delayed IVOS (Med = 6.0 days, IQR = 2.00), u = 507.5, p < 0.001. A one year projection of MYR 54 680.72 could have been saved if early IVOS have been practiced. Conclusion: Early IVOS therapy had proven to cause a significant reduction in the treatment cost as well as length of hospital stay (LOS). We should emphasize on early IVOS in our daily clinical practice as this study shows the potential benefit toward patient as well as the health care facility. An education and feedback session followed by intervention involving multidisciplinary team is necessary to improve the level of current practice of IVOS.

Effectiveness of Dimethyl Fumarate in Patients With Relapsing Multiple Sclerosis Switching After Suboptimal Response to Glatiramer Acetate, Including Patients With Early Multiple Sclerosis: Subgroup Analysis of RESPOND.

IntroductionThis post hoc subset analysis of RESPOND evaluated the effectiveness of dimethyl fumarate (DMF) 240 mg twice daily in patients with relapsing multiple sclerosis (RMS) after suboptimal response to glatiramer acetate (GA; “first switch” patients), including patients with early MS (“early MS switch” patients).MethodsPatients had discontinued GA due to suboptimal response and initiated DMF treatment within 60 days after enrollment. Relapse data were collected from medical records. First switch patients had had one prior approved MS therapy (GA) before initiating DMF treatment. Early MS switch patients were first switch patients with baseline Patient-Reported Expanded Disability Status Scale (PR-EDSS) score ≤ 3.5, ≤ 1 relapses in the past 1 year, or both.ResultsAmong first switch patients (n = 231), the annualized relapse rate (ARR) was 0.48 (95% confidence interval [CI] 0.40–0.58) for 12 months before DMF initiation and 0.11 (95% CI 0.06–0.18) for 12 months after DMF initiation, a 78% decrease in ARR. Among early MS switch patients with baseline PR-EDSS score ≤ 3.5 (n = 120), ≤ 1 relapses in the prior year (n = 219), or both (n = 114), the ARRs (95% CIs) for 12 months before DMF initiation were 0.47 (0.37–0.59), 0.37 (0.32–0.44), and 0.39 (0.31–0.49), respectively; values for 12 months after DMF initiation were 0.06 (0.02–0.19), 0.09 (0.05–0.17), and 0.06 (0.02–0.20), respectively, an 87, 75, and 83% decrease in ARR. The proportion of patients relapse-free 12 months after DMF initiation versus 12 months before were 94 versus 59% in first switch patients, and 97 versus 58%, 94 versus 63%, and 97 versus 61% in early MS switch patients in the PR-EDSS score ≤ 3.5, ≤ 1 relapses in the prior year, or PR-EDSS score ≤ 3.5 and ≤ 1 relapses subgroups, respectively. After 12 months of DMF treatment, most patient-reported outcomes scores showed significant improvement.ConclusionsDMF may be an effective treatment option in first switch and early MS switch patients with RMS who experience a suboptimal response to GA.Trial RegistrationClinicalTrials.gov identifier: NCT01903291.Electronic supplementary materialThe online version of this article (10.1007/s40120-020-00223-2) contains supplementary material, which is available to authorized users.

Is Early Oral Antimicrobial Switch Useful for Less Critically Ill Adults with Community-Onset Bacteraemia in Emergency Departments?

To compare prognoses and adverse events between bacteraemic patients in the emergency department (ED) who received an early antimicrobial IV-to-PO switch and those treated with late or no IV-to-PO switch, an 8-year multicentre cohort consisting of adults with community-onset bacteraemia was conducted. The clinical characteristics and outcomes were compared in matched cohorts by the closest propensity score calculated based on the independent determinants of 30-day mortality identified by the multivariate regression model. Of the 6664 hospitalised patients who received no or late IV-to-PO switch, 2410 were appropriately matched with 482 patients treated with early IV-to-PO switch and discharged from the ED. There were no significant differences between the two matched groups in their baseline characteristics, including the patient demographics, severity and types of comorbidities, severity and sources of bacteraemia, and the 15- and 30-day mortality rates. Notably, in addition to the shorter lengths of intravenous antimicrobial administration and hospital stay, less phlebitis and lower antimicrobial costs were observed in patients who received an early IV-to-PO switch. Similarity was observed in the clinical failure rates between the two groups. Furthermore, the inappropriate administration of empirical antibiotics and inadequate source control were identified as the only independent determinants of the post-switch 30-day crude mortality in patients who received an early IV-to-PO switch. In conclusion, for less critically ill adults with community-onset bacteraemia who received appropriate empirical antimicrobial therapy and adequate source control, an early IV-to-PO switch might be safe and cost-effective after a short course of intravenous antimicrobial therapy.

Children Diagnosed with Acute Leukemia of Ambiguous Lineage (ALAL) Benefit from Acute Myeloid Leukemia (AML) Treatment Protocols: A Retrospective Analysis from a Single Center

Background:Acute Leukemia of Ambiguous Lineage (ALAL) is a very rare type of leukemia, comprising 2%-5% of Acute Leukemias (AL). There is a lack of a uniform definition, with two different classification systems used (EGIL and WHO 2008/2016), making the optimal chemotherapy approach undetermined. Patients and Methods:The medical records of newly diagnosed ALAL patients (BAL based on the EGIL criteria or ALAL based on the 2008/2016 WHO criteria), who were admitted to our hospital from January 2012 to August 2020, were retrospectively reviewed. Patients characteristics including age, sex, blood count, blasts in bone marrow and peripheral blood, morphology, immunophenotyping, and cytogenetic/molecular studies were obtained. Treatment methods and outcome data including induction chemotherapy, complete remission (CR), relapse, use of Hematopoietic Stem Cell Transplantation (HSCT) in first CR (CR1), and death were reviewed. Results:Among a total of 168 newly diagnosed patients with AL, 7 (4.17%) patients (5 male &amp; 2 female), fulfilled prerequisites of ALAL/MPAL. The median age at diagnosis was 5 years (range 1-14 years). Distinct dimorphic lymphoid and myeloid (monocytic) blast populations were present in one case with bilineal leukemia, as well as in two cases of biphenotypic leukemia. The remaining cases had morphologic and cytochemical features of Acute Myeloid Leukemia (AML), French-American-British (FAB): M1, M5 subtypes in two cases and Acute Lymphoblastic Leukemia (ALL) FAB L1-L2 subtype in one case. One case presented with early switch of lineage from ALL at diagnosis to AML M5 at the end of induction treatment. The AML directed regimen was associated with better complete remission rate at the end of induction treatment (CR 100%) compared to the ALL directed regimen (CR 0%). It is of note that the two patients that failed to achieve CR with ALL directed chemotherapy did respond to the AML induction treatment. Six patients underwent HSCT in CR1. One patient relapsed and underwent HSCT in CR2, but succumbed due to treatment related mortality during the transplantation period. At a median follow-up of 3.7 years (range 1-8 years) the 5-year overall survival (OS) and the event free survival (EFS) were 80% and 60%, respectively. Conclusions:Considering that ALAL is a very rare leukemia, the optimal treatment approach remains a dilemma for many clinicians. Although patient numbers are small and follow-up periods are short, the use of AML treatment protocols for ALAL appears to be promising and efforts need to be made on an international collaborative scale. Disclosures Kattamis: Novartis:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Vertex:Membership on an entity's Board of Directors or advisory committees;Genesis Pharma SA:Membership on an entity's Board of Directors or advisory committees;Apopharma/Chiesi:Honoraria, Speakers Bureau;Celgene/BMS:Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Ionis:Membership on an entity's Board of Directors or advisory committees;Agios:Consultancy;Vifor:Membership on an entity's Board of Directors or advisory committees.

Early Switch from Intravenous to Oral Therapy in Hospitalized Patients in Neuroscience Center at KFMC: A Cost-minimization Approach

Early Switch from Intravenous to Oral Therapy in Hospitalized Patients in Neuroscience Center at KFMC: A Cost-minimization Approach

Pancreatic \u03b2-cells respond to fuel pressure with an early metabolic switch

Pancreatic β-cells become irreversibly damaged by long-term exposure to excessive glucose concentrations and lose their ability to carry out glucose stimulated insulin secretion (GSIS) upon damage. The β-cells are not able to control glucose uptake and they are therefore left vulnerable for endogenous toxicity from metabolites produced in excess amounts upon increased glucose availability. In order to handle excess fuel, the β-cells possess specific metabolic pathways, but little is known about these pathways. We present a study of β-cell metabolism under increased fuel pressure using a stable isotope resolved NMR approach to investigate early metabolic events leading up to β-cell dysfunction. The approach is based on a recently described combination of 13C metabolomics combined with signal enhanced NMR via dissolution dynamic nuclear polarization (dDNP). Glucose-responsive INS-1 β-cells were incubated with increasing concentrations of [U-13C] glucose under conditions where GSIS was not affected (2–8 h). We find that pyruvate and DHAP were the metabolites that responded most strongly to increasing fuel pressure. The two major divergence pathways for fuel excess, the glycerolipid/fatty acid metabolism and the polyol pathway, were found not only to operate at unchanged rate but also with similar quantity.

Nintedanib and a bi-specific anti-VEGF/Ang2 nanobody selectively prevent brain metastases of lung adenocarcinoma cells

Brain metastases (BM) are an ever-increasing challenge in oncology, threatening quality of life and survival of many cancer patients. The majority of BM originate from lung adenocarcinoma, and stage III patients have a risk of 40–50% to develop BM in the first years of disease onset. As therapeutic options are limited, prevention of their occurrence is an attractive concept. Here we investigated whether Nintedanib (BIBF 1120), a tyrosine kinase inhibitor (TKI) targeting the VEGF pathway approved for lung adenocarcinoma, and the dual anti-VEGF-A/Ang2 nanobody BI836880 have the potential to prevent BM formation. A mouse model of brain metastasis from lung adenocarcinoma was used in which tumor cells were injected intracardially. Metastases formation occurred inside and outside of the brain and was followed by MRI, IVIS, and immunohistochemistry. BM were reduced in volume and number by both Nintedanib and the dual anti-VEGF-A/Ang2 nanobody, which translated into improved survival. Both compounds were able to normalize cerebral blood vessels at the site of brain metastatic lesions. Extracranial metastases, however, were not reduced, and meningeal metastases only partially. Interestingly, unspecific control IgG also lead to brain vessel normalization and reduction of brain and meningeal metastases. This data indicates a brain-specific group effect of antiangiogenic compounds with respect to metastasis prevention, most likely by preventing an early angiogenic switch. Thus, Nintedanib and BI836880 are promising candidates for future BM preventive study concepts in lung adenocarcinoma patients.

Immunovirological treatment outcomes after 2 years of antiretroviral therapy in children living with the human immune deficiency virus in Lagos Nigeria

Background/objective: The World Health Organization (WHO) recommends routine assessment of antiretroviral treatment outcomes to detect treatment failure early and prevent the development of drug resistance. The aim of this study was to describe treatment outcomes of antiretroviral therapy (ART) over 2 years in children living with the human immune deficiency virus enrolled in the paediatric HIV clinic at the Lagos UniversityTeaching Hospital (LUTH).Materials and methods: This was a retrospective study of antiretroviral treatment outcomes in 278 children receiving antiretroviral therapy at the paediatric HIV clinic of LUTH. Demographic, clinical and laboratory data were retrospectively collected from clinical records of pediatric patientswho received antiretroviral therapy for 2 years ( from November 2015 to December 2017) . Virological failure was defined as viral load &gt; 400 copies/ml and immunological failure was defined as a CD4 count &lt;100 cells/mm3 or CD4 % &lt;15% after receiving antiretroviral agents for 12 months. Data was analysed using graph pad prism version 5.0.Results: After 12 months on antiretroviral therapy (ART), 101 (36%) had virological failure while 14 (5%) and 36 (13%) failed immunologically [CD4 count &lt;100 cells/mn3 and CD4 &lt;15% respectively]. Virological blips were observed at 24 months in 6.1% of patients while immunovirological discordance occurred in 30% of patients (poor virological clearance despite good immunological recovery) . High baseline viral load (&gt;5000 copies/ml), poor adherence (&lt;95%) and low baseline CD4 counts (101-249 cells/mn3) were significantly associated with virological failure, while low baseline CD4 counts (&lt;350 cells/mn3) and poor adherence (&lt;95%) were significantly associated with immunologic failure.Conclusion: The treatment outcomes observed in this study are similar to those reported in earlier studies. At 1 and 2 years of antiretroviral therapy , there was immune restoration however 101 (36%) and 87 (31%) respectively had virological failure despite good adherence to therapy and good Immunological restoration. This calls for early initiation and switch to second and third line drugs .&#x0D; Key words: Human immunodeficiency virus (HIV), zidovudine, lamivudine, nevirapine, virological blips, immunovirological discordance , children, Nigeria.

Short Course and Early Switch of Vigabatrin for Infantile spasms

Short Course and Early Switch of Vigabatrin for Infantile spasms

Inhibiting Histone Deacetylases in Human Macrophages Promotes Glycolysis, IL-1β, and T Helper Cell Responses to Mycobacterium tuberculosis.

Tuberculosis (TB) is the leading infectious killer in the world. Mycobacterium tuberculosis (Mtb), the bacteria that causes the disease, is phagocytosed by alveolar macrophages (AM) and infiltrating monocyte-derived macrophages (MDM) in the lung. Infected macrophages then upregulate effector functions through epigenetic modifications to make DNA accessible for transcription. The metabolic switch to glycolysis and the production of proinflammatory cytokines are key effector functions, governed by epigenetic changes, that are integral to the ability of the macrophage to mount an effective immune response against Mtb. We hypothesised that suberanilohydroxamic acid (SAHA), an FDA-approved histone deacetylase inhibitor (HDACi), can modulate epigenetic changes upstream of the metabolic switch and support immune responses during Mtb infection. The rate of glycolysis in human MDM, infected with Mtb and treated with SAHA, was tracked in real time on the Seahorse XFe24 Analyzer. SAHA promoted glycolysis early in the response to Mtb. This was associated with significantly increased production of IL-1β and significantly reduced IL-10 in human MDM and AM. Since innate immune function directs downstream adaptive immune responses, we used SAHA-treated Mtb-infected AM or MDM in a co-culture system to stimulate T cells. Mtb-infected macrophages that had previously been treated with SAHA promoted IFN-γ, GM-CSF, and TNF co-production in responding T helper cells but did not affect cytotoxic T cells. These results indicate that SAHA promoted the early switch to glycolysis, increased IL-1β, and reduced IL-10 production in human macrophages infected with Mtb. Moreover, the elevated proinflammatory function of SAHA-treated macrophages resulted in enhanced T helper cell cytokine polyfunctionality. These data provide an in vitro proof-of-concept for the use of HDACi to modulate human immunometabolic processes in macrophages to promote innate and subsequent adaptive proinflammatory responses.

Feasibility of early switch to oral antibiotic in brain abscesses and empyema: a multicentre retrospective study.

Feasibility of early switch to oral antibiotic in brain abscesses and empyema: a multicentre retrospective study.

DUX4r, ZNF384r and PAX5-P80R mutated B-cell precursor acute lymphoblastic leukemia frequently undergo monocytic switch.

Recently, we described B-cell precursor acute lymphoblastic leukemia (BCP-ALL) subtype with an early switch to the monocytic lineage and the loss of the B-cell immunophenotype, including CD19 expression. Thus far, the genetic background has remained unknown. Among 726 children consecutively diagnosed with BCP-ALL, 8% patients experienced a switch detectable by flow cytometry (FC). Using exome and RNA sequencing, the switch was found to positively correlate with three different genetic subtypes: PAX5-P80R mutation (five cases with switch of five), rearranged (DUX4r) (30 cases of 41) and rearranged (ZNF384r) (four cases of ten). Expression profiles or phenotypic patterns correlated with genotypes, but within each genotype no cases who subsequently switched could be indentified. If switching was not taken into account, the B-cell-oriented FC assessment underestimated the minimal residual disease level. For patients with PAX5-P80R, a discordance between FC-determined and polymerase chain reactiondetermined minimal residual disease was found on day 15, resulting from a rapid loss of the B-cell phenotype. Discordance on day 33 was observed in all the DUX4r, PAX5-P80R and ZNF384r subtypes. Importantly, despite the substantial phenotypic changes, possibly even challenging the appropriateness of BCP-ALL therapy, the monocytic switch was not associated with a higher incidence of relapse and poorer prognosis in patients undergoing standard ALL treatment.

Efficacy of Early Oral Switch with β-Lactams for Low-Risk Staphylococcus aureus Bacteremia.

The aim of this study was to assess the safety of early oral switch (EOS) prior to 14 days for low-risk Staphylococcus aureus bacteremia (LR-SAB), which is the primary treatment strategy used at our institution. The usual recommended therapy is 14 days of intravenous (i.v.) antibiotics. All patients with SAB at our hospital were identified between 1 January 2014 and 31 December 2018. Those meeting low-risk criteria (health care-associated, no evidence of deep infection or demonstrated involvement of prosthetic material, and no further positive blood cultures after 72 h) were included in the study. The primary outcome was occurrence of a SAB-related complication within 90 days. There were 469 SAB episodes during the study period, 100 (21%) of whom met inclusion criteria. EOS was performed in 84 patients. In this group, line infection was the source in 79%, methicillin-susceptible S. aureus caused 95% of SABs and 74% of patients received i.v. flucloxacillin. The median durations of i.v. and oral antibiotics in the EOS group were 5 days (interquartile range [IQR], 4 to 6) and 10 days (IQR, 9 to 14), respectively. A total of 71% of patients received flucloxacillin as their EOS agent. Overall, 86% of oral step-down therapy was with beta-lactams. One patient (1%) undergoing EOS had SAB relapse within 90 days. No deaths attributable to SAB occurred within 90 days. In this low-MRSA-prevalence LR-SAB cohort, EOS was associated with a low incidence of SAB-related complications. This was achieved with oral beta-lactam therapy in most patients. Larger prospective studies are needed to confirm these findings.

Results of dexamethasone intravitreal implant (Ozurdex) in diabetic macular edema patients: Early versus late switch.

To assess the functional and anatomical outcomes of intravitreal dexamethasone implant Ozurdex® in eyes with diabetic macular edema that did not adequately respond to vascular endothelial growth factor inhibitors. Multicenter, retrospective, and real-life case series study conducted on consecutive diabetic macular edema patients who underwent treatment with one or more dexamethasone implant injections and were followed up for a minimum of 12months. Subjects were divided into three groups: I-naïve patients, II-previously treated eyes that received three intravitreal antivascular endothelial growth factor inhibitors injections before the study (early switch), and III-previously treated eyes that received >3 intravitreal antivascular endothelial growth factor inhibitors injections before the study (late switch). Primary endpoints were best-corrected visual acuity and central retinal thickness at month12. A total of 129 eyes (21 naïve and 108 previously treated, Group II: 32 and Group III: 76) were included. At month12, best-corrected visual acuity significantly improved from 0.27 ± 0.23 and 0.31 ± 0.22 at baseline to 0.36 ± 0.25 and 0.37 ± 0.23 at month12 in naïve and previously treated eyes, respectively, and p = 0.0063 and 0.0060, respectively. Central retinal thickness, in naïve and previously treated eyes, was significantly reduced from 483.0 ± 143.4 and 431.3 ± 115.5 µm, at baseline, to 278.8 ± 72.1 and 269.3 ± 66.2 µm, at month12, respectively, and p < 0.0001 each, respectively. Best-corrected visual acuity improvement was significantly greater in both absolute and percentage values, p = 0.0393 and 0.0118, respectively, in Group II than in Group III. In eyes with insufficient response to antivascular endothelial growth factor inhibitors, switching to dexamethasone at the time to 3-monthly antivascular endothelial growth factor inhibitors injections provided better functional outcomes than those that received >3 antivascular endothelial growth factor inhibitors injections.

Early switch/early discharge opportunities for hospitalized patients with methicillin resistant Staphylococcus aureus complicated skin and soft tissue infections: Saudi Arabia and United Arab Emirates

ObjectivesTo describe opportunities for early switch (ES) from intravenous (IV) to oral (PO) antibiotics and early discharge (ED) of patients hospitalized in the Kingdom of Saudi Arabia (KSA) and the United Arab Emirates (UAE) with methicillin-resistant Staphylococcus aureus (MRSA) complicated skin and soft tissue infections (cSSTIs). MethodsThis retrospective medical chart review study enrolled physicians from 16 KSA and UAE sites to collect data for 107 MRSA cSSTI patients. ResultsActual length of MRSA-active treatment was 13.3±9.3 mean days in KSA and 11.2±3.9 mean days in UAE, with a mean of 11.8±9.3 days of MRSA-targeted IV therapy in KSA and 10.7±4.3 days in UAE. 12.5% in KSA met ES criteria and potentially could have discontinued IV therapy 4.0±2.9 days sooner; 44.0% in UAE could have discontinued 6.6±3.6 days sooner. Patients were hospitalized for a mean 28.6±45.0 days in KSA and 13.1±5.9 days in UAE. 25.0% in KSA and 48.0% in UAE met ED criteria and potentially could have been discharged 6.1±8.0 days earlier in KSA and 7.9±5.0 days earlier in UAE. ConclusionsA significant proportion of patients hospitalized for MRSA cSSTI could be eligible for ES or ED opportunities, resulting in potential for reductions in IV and bed days.

Early switch from intravenous to oral antibiotic therapy in patients with cancer who have low-risk neutropenic sepsis (the EASI-SWITCH trial): study protocol for a randomised controlled trial

BackgroundNeutropenic sepsis remains a common treatment complication for patients receiving systemic anti-cancer treatment. The UK National Institute for Health and Care Excellence have not recommended switching from empirical intravenous antibiotics to oral antibiotics within 48 h for patients assessed as low risk for septic complications because of uncertainty about whether this would achieve comparable outcomes to using intravenous antibiotics for longer. The UK National Institute for Health Research funded the EASI-SWITCH trial to tackle this uncertainty.MethodsThe trial is a pragmatic, randomised, non-inferiority trial that aims to establish the clinical and cost-effectiveness of early switching from intravenous to oral antibiotics in cancer patients with low-risk neutropenic sepsis. Patients ≥ 16 years, receiving systemic anti-cancer treatment (acute leukaemics/stem cell transplants excluded), with a temperature of > 38 °C, neutrophil count ≤ 1.0 × 109/L, MASCC (Multinational Association of Supportive Care in Cancer) score ≥ 21 and receiving IV piperacillin/tazobactam or meropenem for less than 24 h are eligible to participate. Patients are randomised 1:1 either (i) to switch to oral ciprofloxacin and co-amoxiclav within 12–24 h of commencing intravenous antibiotics, completing at least 5 days total antibiotics (intervention), or (ii) to continue intravenous antibiotics for at least 48 h, with ongoing antibiotics being continued at the physician’s discretion (control). Patients are discharged home when their physician deems it appropriate. The primary outcome measure is a composite of treatment failures as assessed at day 14. The criteria for treatment failure include fever persistence or recurrence 72 h after starting intravenous antibiotics, escalation from protocolised antibiotics, hospital readmission related to infection/antibiotics, critical care support or death. Based on a 15% treatment failure rate in the control group and a 15% non-inferiority margin, the recruitment target is 230 patients.DiscussionIf the trial demonstrates non-inferiority of early switching to oral antibiotics, with potential benefits for patient quality of life and resource savings, this finding will have significant implications for the routine clinical management of those with low-risk neutropenic sepsis.Trial registrationISRCTN: 84288963. Registered on the 1 July 2015. https://doi.org/10.1186/ISRCTN84288963.EudraCT: 2015-002830-35.

Highly active RRMS and ocrelizumab after failure of alemtuzumab therapy

BackgroundA high multiple sclerosis activity while on alemtuzumab is rather uncommon compared to moderate-efficacy drugs. The purpose of this case report is to present a case of a 37-year-old female patient with bronchial asthma and no other medical history, whose disease activity required switching from dimethyl fumarate to fingolimod, then to alemtuzumab and finally to ocrelizumab.Case presentationIn our patient, two severe attacks were observed and treated after administration of the first pulse of alemtuzumab. After six months of therapy, patient’s immunological profile showed the expected decrease in CD4+ and CD8+ T-cells and, markedly increased values of CD19+ B-cells. Surprisingly memory B-cells, which typically repopulate very slowly following alemtuzumab treatment, were above baseline levels. Regular administration of ocrelizumab based on a standardised scheme, after the alemtuzumab therapy failure, resulted in the stabilisation of the patient’s condition both clinically and radiologically.ConclusionThus, when the alemtuzumab treatment is unsuccessful, the authors recommend testing T- and B-cell levels and proceeding with an early switch to ocrelizumab if high B-cell counts are found.

Short-term results of early switch from Ranibizumab to Aflibercept in poor or non responder age related macular degeneration in clinical practice

BackgroundTo evaluate the change in best corrected visual acuity (VA) and central macular thickness (CMT) following treatment with intravitreal aflibercept (AFL) in patients poorly responders or non responders to ranibizumab (RBZ).MethodsCharts of patients injected with RBZ from January 2016 to December 2018 (548 cases) due to neovascular age-related macular degeneration (nAMD) were reviewed. Fifty-six cases met our criteria for poor responders to RBZ (CMT decreased between 5 and 15% over treatment) or for non responders to RBZ (CMT decreased less than 5% or increased over treatment).ResultsAfter the third AFL injection, CMT decreased from 384.38 ± 123.20 μm to 296.18 ± 70.52 μm in the non-responder group and from 320.00 ± 82.05 μm to 282.27 ± 56.86 μm in the poor responder group. Although decrease in macular thickness was overall achieved 3 months after switching to AFL, it was not translated in VA improvement.Conclusionsit was observed that nAMD patients classified as RBZ non-responders tend to respond better to AFL than RBZ poor-responders anatomically, without correspondent improvement in VA.