What are the needs in oral antitumor therapy? An analysis of patients' and practitioners' preferences.

Background: Since the European approval of CDK4/6 inhibitors in 2016, the treatment of patients with hormone-receptor-positive, HER2-negative metastatic breast cancer has changed significantly. Compared with chemotherapy, endocrine-based therapy has different treatment regimens and is associated with new side effects. Oral therapy aims for optimal drug efficacy and long treatment times while maintaining maximum independence and quality of life resulting in the conservation of medical staff resources. Methods: A monocentric analysis of therapy preferences of practitioners (25 nurses and physicians) and patients (11 on endocrine monotherapy, 17 on endocrine-based therapy, and 14 on intravenous chemotherapy) was performed using specific questionnaires. Preferences were assessed using a four-point Likert scale or bidirectional response options. Results: All patients were highly supportive of oral therapy (mean agreement score on the Likert scale 1.3, p < 0.001 vs. all other options) and a consultation interval of 4 weeks (2.0, p = 0.015 vs. 3 weeks). Practitioners also preferred oral therapy (1.4) and visits every 4 weeks (1.6). In general, patients on oral therapies reported higher compatibility of their therapy with daily life than patients on chemotherapy (1.6 and 1.7 vs. 2.6, p = 0.006). Outpatient oncology is the main source of information for all patients, mainly in case of side effects (2.0) and open questions (1.8). Regarding oral antitumor therapy regimens, patients do not show a significant preference for a specific regimen, while practitioners prefer a continuous regimen (1.6) over a 21/7 regimen (21 days on and 7 days off therapy, 2.5). Patients are likely to accept mild side effects (e.g., neutropenia, diarrhea, polyneuropathy, fatigue) and would still adhere to their initial choice of regimen (continuous or 21/7). Only when side effects occur with a severity of CTCAE grade 3 do patients prefer the regimen in which the side effects occur for a shorter period of time. Conclusion: Patients and practitioners prefer oral antitumor therapy-both continuous and 21/7 regimens-over other application forms. Patient education and proper therapy management, supported by additional tools, contribute to the specific management of side effects and high adherence. This allows quality of life to be maintained during long-term therapy with CDK4/6 inhibitors in patients with metastatic breast cancer.

Evaluation of Sequential Oral Versus Intravenous Antibiotic Treatment of Enterococcus faecalis Bloodstream Infections.

BACKGROUND: Intravenous (IV) antibiotics have historically been considered standard of care for treatment of bloodstream infections (BSIs). Recent literature has shown sequential oral (PO) therapy to be noninferior to IV antibiotics for certain pathogens and disease states. However, a gap exists in the literature for BSI caused by Enterococcus faecalis. OBJECTIVE: To compare outcomes of definitive sequential PO therapy to definitive IV therapy in patients with E faecalis BSI. METHODS: Multicenter, retrospective, matched cohort study of adult patients with at least one blood culture positive for E faecalis from January 2017 to November 2022. Patients with polymicrobial BSI, concomitant infections requiring prolonged IV antibiotic therapy, those who did not receive antibiotic therapy, and those who died within 72 hours of index culture were excluded. Subjects were matched based on source of infection in a 2:1 (IV:PO) ratio. The primary outcome was a composite of all-cause mortality and treatment failure. Secondary outcomes included hospital length of stay (LOS), antibiotic duration, and 30-day readmission rate. RESULTS: Of the 186 patients who met criteria for inclusion, there was no statistically significant difference in the primary composite outcome for PO compared to IV therapy (14.5% vs 21.8%; OR 0.53 [0.23-1.25]) or 30-day readmission (17.5% vs 29%; OR 0.53 [0.25-1.13]). Hospital LOS was significantly longer in patients receiving IV-only therapy (6 days vs 14 days; P < 0.001). CONCLUSION AND RELEVANCE: Sequential oral therapy for E faecalis BSI had similar outcomes compared to IV-only treatment and may be considered in eligible patients.

Mycosis Fungoides Presenting With Multiple Tumors on the Face.

An 84-year-old female experienced progressive erythema on her limbs and chest over the past year. Initially managed with topical steroids, the erythema eventually spread throughout her body, forming erosions. A biopsy confirmed the diagnosis of mycosis fungoides (MF) (Stage IIB, T2bN0M0B0). Treatment with oral bexarotene (300 mg/day) and narrow-band UVB therapy showed limited improvement. Electron beam therapy (30 Gy in 10 fractions) applied to facial and plantar tumors resulted in a reduction of the tumors. This case highlights the treatment of tumors of MF on the face showing the effectiveness of combining electron beam therapy with bexarotene.

Oral administration of liposome-encapsulated thymol could alleviate the inflammatory parameters in serum and hippocampus in a rat model of Alzheimer's disease.

BACKGROUND: Neuroinflammation is closely related to Alzheimer's Disease (AD) pathology, hence supplements with anti-inflammatory property could help attenuate the progression of AD. This study was conducted to evaluate the potential anti-inflammatory effects of liposome encapsulated thymol (LET), administered orally, in prevention of Alzheimer in a rat model by anti-inflammatory mechanisms. METHODS: The rats were grouped into six groups (n = 10 animals per group), including Control healthy (Con), Alzheimer's disease (AD) model, AD model treated with free thymol in 40 and 80 mg/kg body weight (TH40 and TH80), AD model treated with LET in 40 and 80 mg/kg of body weight (LET40 and LET80). The behavioral response of step through latency (Passive Avoidance Test), concentrations of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2) and brain-derived neurotrophic factor (BDNF) were assessed in serum and hippocampus. RESULTS: The results showed that significant increase in concentrations of IL-1ß (P = 0.001), IL-6 (P = 0.001), TNF-α (P = 0.001) and COX-2 (P = 0.001) in AD group compared with healthy control rats. AD induction significantly reduced step through latency and revealed deficits in passive avoidance performance. The results also showed the treatment with free thymol especially in higher concentrations and also LTE could decrease serum concentrations of IL-1ß (P < 0.05), IL-6 (P < 0.05), TNF-α (P < 0.05), and COX-2 (P < 0.05) and increase BDNF (P < 0.05) compared with control Alzheimer rats in hippocampus and serum. There were also significant correlations between serum and hippocampus concentrations of IL-1ß (r2 = 0.369, P = 0.001), IL-6 (r2 = 0.386, P = 0.001), TNF-α (r2 = 0.412, P = 0.001), and COX-2 (r2 = 0.357, P = 0.001). It means a closed and positive relation between serum and hippocampus concentrations of IL-1ß, IL-6, TNF-α, and COX-2. CONCLUSIONS: LET demonstrates its ability to attenuate neuroinflammatory reaction in AD model through suppression of IL-1ß, IL-6, and TNF-α and COX-2 indicators. Hence, it can ameliorate AD pathogenesis by declining inflammatory reaction.

Oral Prescription Management.

The treatment of atopic dermatitis (AD) with oral treatments has been limited in the past due to the increased risk of adverse effects associated with oral agents. However, in recent years, a shift toward the minimization of adverse effects has been explored. Although existing treatment options like oral corticosteroids and Immunosuppressive therapies have been utilized for acute flare-ups of AD, their long-term use is limited by adverse effects and the need for lab monitoring. New systemic treatment options such as Janus kinase (JAK) inhibitors are emerging as a promising therapy, due to their quick onset and antipruritic features. However, the black box warning associated with this medication class requires careful selection of appropriate candidates and patient education despite early favorable safety profiles seen in AD trials. Discussion of other oral agents, like antibiotics and antihistamines, and their role in AD management are also clarified.

Effectiveness, Simplification and Persistence of IDegLira in Poorly Controlled People with Type 2 Diabetes: A 4-Year Follow-Up Real-World Study.

INTRODUCTION: Efficacy and safety of the fixed ratio combination of insulin degludec and liraglutide (IDegLira) has been largely documented. However, long-term data are limited. This study aimed at describing persistence in therapy and the effectiveness at 48 months of IDegLira. METHODS: We conducted an observational study based on retrospective chart review. All patients treated with IDegLira during 2018-2022 were included. Data on treatment approaches and clinical outcomes were collected at the first prescription of IDegLira (T0) and after 6, 12, 24, 36, and 48 months. RESULTS: Overall, 156 patients (mean age 68 years, 64.1% men) started IDegLira, of whom 88 (56.4%) were previously treated with basal-oral therapy (BOT) and 68 (43.6%) with basal-bolus schemes (BB). Before starting IDegLira, 23.8% were treated with ≥ 2 oral antihyperglycemic agents in association with insulin; at T0, the proportion decreased to 3.2%. Short-acting insulin was discontinued after the first week. After 48 months, levels of HbA1c were significantly reduced by 1.34% in the BOT group and 1.07% in the BB group (p < 0.0001 in both groups). In the BOT group, FBG levels decreased by about 50 mg/dl and body weight was unchanged. In the BB group, FBG levels decreased by about 40 mg/dl and body weight was significantly reduced by an average of 7.7 kg. Five patients (3.2%) interrupted therapy with IDegLira during 48 months, and no severe hypoglycemia occurred. CONCLUSIONS: Our study emphasizes the important role of IDegLira in maintaining a good metabolic control while minimizing the risk of major hypoglycemia and weight gain in the long term. The substantial simplification of treatment schemes can increase adherence.

In-class transition from bortezomib-based therapy to IRd is an effective approach in newly diagnosed multiple myeloma.

Aim: To compare the effectiveness of in-class transition to all-oral ixazomib-lenalidomide-dexamethasone (IRd) following parenteral bortezomib (V)-based induction versus continued V-based therapy in US oncology clinics. Patients & methods: Non-transplant eligible patients with newly diagnosed multiple myeloma (MM) receiving in-class transition to IRd (N = 100; US MM-6), or V-based therapy (N = 111; INSIGHT MM). Results: Following inverse probability of treatment weighting, overall response rate was 73.2% with IRd versus 57.5% with V-based therapy (p < 0.0001). Median duration of treatment was 10.8 versus 5.3 months (p < 0.0001). Overall, 18/24% of patients discontinued IRd/V-based therapy due to adverse events. Conclusion: IRd after V-based induction was associated with significantly improved overall response rate and duration of treatment than continued V-based combination therapy. Clinical Trial Registration: US MM-6: NCT03173092; INSIGHT MM: NCT02761187 (ClinicalTrials.gov).

Switch to oral antibiotics in Gram-negative bacteraemia: a randomized, open-label, clinical trial.

OBJECTIVES: To evaluate the safety and efficacy of switching from intravenous (IV) to oral antimicrobial therapy in patients with Enterobacterales bacteraemia, after completion of 3-5 days of microbiologically active IV therapy. METHODS: A multicentre, open-label, randomized trial of adults with monomicrobial Enterobacterales bacteraemia caused by a strain susceptible to ≥1 oral beta-lactam, quinolone, or trimethoprim/sulfamethoxazole. Inclusion criteria included completion of 3-5 days of microbiologically active IV therapy, being afebrile and haemodynamically stable for ≥48 hours, and absence of an uncontrolled source of infection. Pregnancy, endocarditis, and neurological infections were exclusion criteria. Randomization, stratified by urinary source of bacteraemia, was to continue IV (IV Group) or to switch to oral therapy (Oral Group). Agents and duration of therapy were determined by the treating physicians. The primary endpoint was treatment failure, defined as death, need for additional antimicrobial therapy, microbiological relapse, or infection-related re-admission within 90 days. Non-inferiority threshold was set at 10% in the 95% CI for the difference in the proportion with treatment failure between the Oral and IV Groups in the modified intention-to-treat population. The protocol was registered at ClinicalTrials.gov (NCT04146922). RESULTS: In the modified intention-to-treat population, treatment failure occurred in 21 of 82 (25.6%) in the IV Group, and 18 of 83 (21.7%) in the Oral Group (risk difference -3.7%, 95% CI -16.6% to 9.2%). The proportions of subjects with any adverse events (AE), serious AE, or AE leading to treatment discontinuation were comparable. DISCUSSION: In patients with Enterobacterales bacteraemia, oral switch, after initial IV antimicrobial therapy, clinical stability, and source control, is non-inferior to continuing IV therapy.

Preferences of people living with HIV for injectable and oral antiretroviral treatment in the Netherlands: a discrete choice experiment.

ABSTRACTInjectable antiretroviral treatment (ART) represents a new effective and potentially more convenient alternative to oral ART for people living with HIV (PLWH). This study assessed preferences of PLWH for long-acting injectable compared with oral ART in the Netherlands. A labelled discrete choice experiment presented 12 choice sets of long-acting injectable and oral ART. PLWH were asked to select their preferred ART, described by six attributes: location of administration, dosing frequency, risk of short-term side effects, drug-drug interaction, forgivability, and food and mealtime restrictions. Random parameters logit and latent class models were used to estimate preferences of PLWH. 98.6% of 76 respondents were experienced oral ART users that had taken ART for a median of 12 years (Q1-Q3: 7.0-20.0). 30 (39.5%) respondents chose long-acting injectable ART in all choice tasks and 22 (28.9%) always chose oral ART. The random parameter model showed that, on average, respondents significantly favoured long-acting injectable ART over oral ART, preferred administration of the long-acting injectable ART at home, and a less frequent regimen. The latent class model confirmed one class strongly preferring long-acting injectable ART and one class slightly preferring oral ART. This study highlights the value for both long-acting injectable and oral ART.

Once-Daily Oral Berotralstat for Long-Term Prophylaxis of Hereditary Angioedema: The Open-Label Extension of the APeX-2 Randomized Trial.

BACKGROUND: Berotralstat is a first-line, once-daily oral plasma kallikrein inhibitor approved for prophylaxis of hereditary angioedema (HAE) attacks in patients 12 years or older. OBJECTIVE: This analysis examined the safety and effectiveness of long-term prophylaxis with berotralstat. METHODS: APeX-2 was a phase 3, parallel-group, multicenter trial in patients with HAE caused by C1-inhibitor deficiency (NCT03485911). Part 1 was a randomized, double-blind, placebo-controlled evaluation of 150 and 110 mg of berotralstat over 24 weeks. In part 2, berotralstat-treated patients continued the same treatment, and placebo-treated patients were re-randomized to 150 or 110 mg of berotralstat for 24 weeks. In part 3, all patients were treated with open-label berotralstat at 150 mg, which could be continued for up to an additional 4 years. In part 3, the primary endpoint was long-term safety and tolerability. Secondary endpoints included HAE attack rates and quality of life (QoL). RESULTS: Eighty-one patients entered part 3. Treatment-emergent adverse events (TEAEs) occurred in 82.7% of patients, with most being mild or moderate in severity. The most common TEAEs were nasopharyngitis, urinary tract infection, abdominal pain, arthralgia, coronavirus infection, and diarrhea. Drug-related TEAEs occurred in 14.8% of patients, but none were serious. For patients who completed 96 weeks of berotralstat treatment (n = 70), the mean (standard error) change in attack rate from baseline was -2.21 (0.20) attacks/mo. Clinically meaningful improvements in QoL were also observed, with the largest improvements in the functioning domain. CONCLUSION: Berotralstat was generally well tolerated, provided rapid and sustained reductions in HAE attacks and improved QoL over 96 weeks.

New Antimicrobials and New Therapy Strategies for Endocarditis: Weapons That Should Be Defended.

The overall low-quality evidence concerning the clinical benefits of different antibiotic regimens for the treatment of infective endocarditis (IE), which has made it difficult to strongly support or reject any regimen of antibiotic therapy, has led to a discrepancy between the available guidelines and clinical practice. In this complex scenario, very recently published guidelines have attempted to fill this gap. Indeed, in recent years several antimicrobials have entered the market, including ceftobiprole, ceftaroline, and the long-acting lipoglycopeptides dalbavancin and oritavancin. Despite being approved for different indications, real-world data on their use for the treatment of IE, alone or in combination, has accumulated over time. Furthermore, an old antibiotic, fosfomycin, has gained renewed interest for the treatment of complicated infections such as IE. In this narrative review, we focused on new antimicrobials and therapeutic strategies that we believe may provide important contributions to the advancement of Gram-positive IE treatment, providing a summary of the current in vitro, in vivo, and clinical evidence supporting their use in clinical practice.

The history of oral decitabine/cedazuridine and its potential role in acute myeloid leukemia.

Decitabine, a member of the 5-azanucleosides, has a dose-dependent mechanism of action in vitro: termination of DNA replication at high doses, and inhibition of DNA methyltransferase at low doses. The alteration of DNA methylation patterns by low-dose decitabine is hypothesized to upregulate genes, which promote myeloblast differentiation. In a phase III clinical trial, low-dose decitabine achieved a superior overall response rate (ORR) when compared with 'treatment choice' [consisting of low-dose cytarabine (80%) and supportive care (20%)] as a frontline treatment for elderly patients with acute myeloid leukemia (AML). Despite an improved ORR, the median overall survival (OS) for elderly patients with AML was poor, <1 year. In turn, venetoclax was added to low-dose decitabine, the combination of which significantly improved the ORR and median OS in elderly patients with AML. Currently, hypomethylating agents are being combined with other novel therapies as investigational strategies for elderly and unfit patients with AML. They are also being evaluated as components of maintenance therapy in patients achieving remission. An oral formulation of decitabine has been developed which relies on the concomitant use of oral cedazuridine to protect against first pass metabolism. This oral formulation, which has been approved in myelodysplastic syndrome, is intended to increase convenience of use and therefore compliance in patients. This review characterizes the evolution of decitabine, its oral formulation, and its future in the treatment of AML.

Congenital Ichthyosis: A Practical Clinical Guide on Current Treatments and Future Perspectives.

Congenital ichthyoses are a group of hereditary disorders of keratinization that are challenging to treat. Affected individuals suffer not only from thickening of the skin but also associated complications such as growth restriction, hearing and eye complications, infections, and thermodysregulation. This clinical review provides a practical roadmap to the longitudinal care of patients with ichthyosis with both general and age- and disease-specific recommendations. The allure of pathogenesis-based and targeted treatments for these monogenetic severe but orphan conditions shines bright as dermatological therapies enter a new era.

Medication Formulation Preference of Mild and Moderate Ulcerative Colitis Patients: a European Survey.

Introduction: Patient adherence is a major challenge for the successful management of any chronic disease, and ulcerative colitis (UC) is no exception. Patient adherence is closely related to patient preference of medication and formulation used. Aim: The aim of this study was to investigate patient and physician perspectives around UC treatment preference. Methods: This study was conducted in France, Germany, Spain, and the UK. Physicians and UK inflammatory bowel disease (IBD) nurses answered an online questionnaire. In addition, adult mild-to-moderate UC patients, treated with oral mesalazine, were invited to answer a 30-min online survey which included a conjoint exercise. Results: 400 patients, 160 physicians, and 20 IBD nurses participated in the survey. 68% of patients were taking tablets and 32% granules. Physicians stated that from their perspective patients are more adherent to tablets than granules (76% vs. 24%), patients tended to have better relief of symptoms with tablets (69% vs. 31%), and patients found tablets to be the most convenient formulation (61% vs. 39%). From the patients' perspective, when questioned which formulation they prefer, 58% answered tablets, 37% granules, and 5% none of these. When patients were asked about some negative attributes of tablets, the highest agreement was for "I would like to take fewer each day" (6.1/10) and "I wish I could take fewer at a time" (5.4/10). Conclusions: The majority of UC patients in this survey prefer the tablet formulation. A high strength tablet overcoming the high pill burden could be a good solution to address patient expectations.

Medication Adherence among Allogeneic Haematopoietic Stem Cell Transplant Recipients: A Systematic Review.

Recipients of a haematopoietic stem cell transplantation (HSCT) may experience issues in medication adherence (MA) when discharged. The primary aim of this review was to describe the oral MA prevalence and the tools used to evaluate it among these patients; the secondary aims were to summarise factors affecting medication non-adherence (MNA), interventions promoting MA, and outcomes of MNA. A systematic review (PROSPERO no. CRD42022315298) was performed by searching the Cumulative Index of Nursing and Allied Health (CINAHL), Cochrane Library, Excerpta Medica dataBASE (EMBASE), PsycINFO, PubMed and Scopus databases, and grey literature up to May 2022 by including (a) adult recipients of allogeneic HSCT, taking oral medications up to 4 years after HSCT; (b) primary studies published in any year and written in any language; (c) with an experimental, quasi-experimental, observational, correlational, and cross-sectional design; and (d) with a low risk of bias. We provide a qualitative narrative synthesis of the extracted data. We included 14 studies with 1049 patients. The median prevalence of MA was 61.8% and it has not decreased over time (immunosuppressors 61.5% [range 31.3-88.8%] and non-immunosuppressors 65.2% [range 48-100%]). Subjective measures of MA have been used most frequently (78.6%) to date. Factors affecting MNA are younger age, higher psychosocial risk, distress, daily immunosuppressors, decreased concomitant therapies, and experiencing more side effects. Four studies reported findings about interventions, all led by pharmacists, with positive effects on MA. Two studies showed an association between MNA and chronic graft-versus-host disease. The variability in adherence rates suggests that the issues are relevant and should be carefully considered in daily practice. MNA has a multifactorial nature and thus requires multidisciplinary care models.

Comparison of Oral and Intravenous Definitive Antibiotic Therapy for Beta-Hemolytic Streptococcus Species Bloodstream Infections from Soft Tissue Sources: a Propensity Score-Matched Analysis.

Beta-hemolytic streptococci are common causes of bloodstream infection (BSI). There is emerging data regarding oral antibiotics for BSI but limited for beta-hemolytic streptococcal BSI. We conducted a retrospective study of adults with beta-hemolytic streptococcal BSI from a primary skin/soft tissue source from 2015 to 2020. Patients transitioned to oral antibiotics within 7 days of treatment initiation were compared to those who continued intravenous therapy, after propensity score matching. The primary outcome was 30-day treatment failure (composite of mortality, infection relapse, and hospital readmission). A prespecified 10% noninferiority margin was used for the primary outcome. We identified 66 matched pairs of patients treated with oral and intravenous antibiotics as definitive therapy. Based on an absolute difference in 30-day treatment failure of 13.6% (95% confidence interval 2.4 to 24.8%), the noninferiority of oral therapy was not confirmed (P = 0.741); on the contrary, the superiority of intravenous antibiotics is suggested by this difference. Acute kidney injury occurred in two patients who received intravenous treatment and zero who received oral therapy. No patients experienced deep vein thrombosis or other vascular complications related to treatment. In patients treated for beta-hemolytic streptococcal BSI, those who transitioned to oral antibiotics by day 7 showed higher rates of 30-day treatment failure than propensity-matched patients. This difference may have been driven by underdosing of oral therapy. Further investigation into optimal antibiotic choice, route, and dosing for definitive therapy of BSI is needed.

Effectiveness of oral cephalexin in antibiotic-course completion for methicillin-susceptible Staphylococcus aureus-induced bacteremic vertebral osteomyelitis.

BACKGROUND: Methicillin-susceptible Staphylococcus aureus (MSSA) is the most common causative microorganism of pyogenic vertebral osteomyelitis (PVO). Although oral antimicrobial therapy with first-generation cephalosporins can treat MSSA infection, data on PVO are scarce. This study evaluated the treatment efficacy of cephalexin as oral antibiotic therapy for MSSA-induced PVO. METHODS: This retrospective study included adult patients treated with oral cephalexin as the completing treatment for PVO with MSSA bacteremia from 2012 to 2020. Treatment effectiveness of cephalexin was evaluated by comparing improvement (5-point scale; score ≥ 4/5 indicates treatment success) in symptoms and laboratory and imaging results between intravenous antimicrobial and oral cephalexin treatment. RESULTS: Among 15 participants (8 [53%] women; median [interquartile range, IQR], age 75 [67.5-80.5] years; Charlson Comorbidity Index 2 [0-4]), 10 (67%) had lumbar spine lesions, 12 (80%) had spinal abscesses, and 4 (27%) had remote abscesses; no patients had concomitant endocarditis. In 11 patients with normal renal function, cephalexin 1,500-2,000 mg/day was administered. Five patients (33%) underwent surgery. Median (IQR; range) duration (days) of intravenous antibiotics, cephalexin, and total treatment was 36 (32-61; 21-86), 29 (19-82; 8-251), and 86 (59-125; 37-337), respectively. Cephalexin had an 87% treatment success rate without recurrence during a median follow-up of 119 (IQR, 48.5-350) days. CONCLUSIONS: In patients with MSSA bacteremia and PVO, antibiotic treatment completion with cephalexin is a reasonable option, even in cases with spinal abscess, if at least 3 weeks of effective intravenous antimicrobial therapy is provided.

Worsening of chronic heart failure: definition, epidemiology, management and prevention. A clinical consensus statement by the Heart Failure Association of the European Society of Cardiology.

Episodes of worsening symptoms and signs characterize the clinical course of patients with chronic heart failure (HF). These events are associated with poorer quality of life, increased risks of hospitalization and death and are a major burden on healthcare resources. They usually require diuretic therapy, either administered intravenously or by escalation of oral doses or with combinations of different diuretic classes. Additional treatments may also have a major role, including initiation of guideline-recommended medical therapy (GRMT). Hospital admission is often necessary but treatment in the emergency service or in outpatient clinics or by primary care physicians has become increasingly used. Prevention of first and recurring episodes of worsening HF is an essential component of HF treatment and this may be achieved through early and rapid administration of GRMT. The aim of the present clinical consensus statement by the Heart Failure Association of the European Society of Cardiology is to provide an update on the definition, clinical characteristics, management and prevention of worsening HF in clinical practice.

Adherence to oral hormonal therapy in advanced prostate cancer: a scoping review.

Background: Orally administrated agents play a key role in the management of prostate cancer, providing a convenient and cost-effective treatment option for patients. However, they are also associated with adherence issues which can compromise therapeutic outcomes. This scoping review identifies and summarizes data on adherence to oral hormonal therapy in advanced prostate cancer and discusses associated factors and strategies for improving adherence. Methods: PubMed (inception to 27 January 2022) and conference databases (2020-2021) were searched to identify English language reports of real-world and clinical trial data on adherence to oral hormonal therapy in prostate cancer using the key search terms 'prostate cancer' AND 'adherence' AND 'oral therapy' OR respective aliases. Results: Most adherence outcome data were based on the use of androgen receptor pathway inhibitors in metastatic castration-resistant prostate cancer (mCRPC). Self-reported and observer-reported adherence data were used. The most common observer-reported measure, medication possession ratio, showed that the vast majority of patients were in possession of their medication, although proportion of days covered and persistence rates were considerably lower, raising the question whether patients were consistently receiving their treatment. Study follow-up for adherence was generally around 6 months up to 1 year. Studies also indicate that persistence may drop further with longer follow-up, especially in the non-mCRPC setting, which may be a concern when years of therapy are required. Conclusions: Oral hormonal therapy plays an important role in the treatment of advanced prostate cancer. Data on adherence to oral hormonal therapies in prostate cancer were generally of low quality, with high heterogeneity and inconsistent reporting across studies. Short study follow-up for adherence and focus on medication possession rates may further limit relevance of available data, especially in settings that require long-term treatment. Additional research is required to comprehensively assess adherence.

Evaluation of Oral Tebipenem as a Step-Down Therapy following Intravenous Ertapenem against Extended-Spectrum ß-Lactamase-Producing Escherichia coli in a Hollow-Fiber In Vitro Infection Model.

Tebipenem is an orally bioavailable carbapenem in development for the treatment of patients with complicated urinary tract infections. Herein, we describe the results of studies designed to evaluate tebipenem's potential as an oral (p.o.) transition therapy from intravenous (i.v.) ertapenem therapy for the most common uropathogen, Escherichia coli. These studies utilized a 7-day hollow-fiber in vitro infection model and 5 extended-spectrum ß-lactamase-producing E. coli challenge isolates. Human free-drug serum concentration-time profiles for tebipenem 600 mg p.o. every 8 h and ertapenem 1 g i.v. every 24 h were simulated in the hollow-fiber in vitro infection model. Samples were collected for bacterial density and drug concentration determination over the 7-day study period. Generally, ertapenem monotherapy resulted in a greater reduction in bacterial density than did tebipenem monotherapy. In the treatment arms in which ertapenem dosing was stopped following dosing for 1 or 3 days, immediate bacterial regrowth occurred and matched that of the growth control. Finally, in the treatment arms in which ertapenem dosing was stopped following dosing for 1 or 3 days and tebipenem dosing was initiated for the remainder of the 7-day study, the intravenous-to-oral transition regimen reduced bacterial burdens and prevented regrowth. Given that transition from intravenous to oral antibiotic therapy has been shown to reduce hospital length of stay, nosocomial infection risk, and cost, and improve patient satisfaction, these data demonstrate tebipenem's potential role as an oral transition agent from intravenous antibiotic regimens within the antibiotic stewardship paradigm.