Asthma is a common, multifaceted respiratory disease with a major impact on quality of life. Despite increased insights into mechanisms underlying various asthma phenotypes and endotypes and the availability of targeted biologic treatment options, the disease remains uncontrolled in a substantial proportion of patients with risk of exacerbations, requiring systemic corticosteroids, and with progressive disease. Current international guidelines advocate for a personalized management approach to patients with uncontrolled severe asthma. The European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) asthma expert panel was convened to discuss strategies to optimize asthma care and to prevent systemic corticosteroid overuse and disease progression. In this meeting report, we summarize current concepts and recommendations and provide a rationale to implement personalized asthma management at earlier stages of the disease. The ultimate goal is to move away from the current one-size-fits-most concept, which focuses on a symptom-driven treatment strategy, and shift toward a phenotype- and endotype-targeted approach aimed at curbing the disease course by improving clinical outcomes and preserving health-related quality of life. Herein, we provide a consensus view on asthma care that advocates a holistic approach and highlight some unmet needs to be addressed in future clinical trials and population studies.
- MeSH
- Anti-Asthmatic Agents * therapeutic use MeSH
- Asthma * prevention & control therapy drug therapy MeSH
- Precision Medicine MeSH
- Remission Induction MeSH
- Consensus MeSH
- Quality of Life MeSH
- Humans MeSH
- Disease Management MeSH
- Disease Progression MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Consensus Development Conference MeSH
BACKGROUND AND OBJECTIVE: Non-muscle-invasive bladder cancer (NMIBC) poses a significant clinical challenge, particularly when failing bacillus Calmette-Guérin (BCG) therapy, necessitating alternative treatments. Despite radical cystectomy being the recommended treatment, many patients are unfit or unwilling to undergo this invasive procedure, highlighting the need for effective bladder-sparing therapies. This review aims to summarize and report the evidence on the efficacy and to estimate the costs of bladder-preserving strategies used in NMIBC recurrence after failure of intravesical BCG therapy. METHODS: We systematically searched online databases for prospective studies investigating intravesical therapy, systemic therapy, or combination of both in patients treated previously with BCG. Owing to significant heterogeneity across the studies, a meta-analysis was inappropriate. A sensitivity analysis was performed in an exploratory manner. We used a decision-analytic Markov model to compare novel U.S. Food and Drug Administration-approved treatments with a 2-yr time horizon. KEY FINDINGS AND LIMITATIONS: A total of 57 studies published between 1998 and 2024, with 68 unique study arms and consisting of 2589 patients, were identified. The 3-mo overall response rate (ORR) across all studies, complete response rate (CRR) in concomitant carcinoma in situ (CIS) or CIS only disease, and recurrence-free rate (RFR) in papillary disease were estimated to be 52.4% (95% confidence interval [CI]: 45.4-59.2), 52.8% (95% CI: 42.9-62.6), and 26.4% (95% CI: 13.3-45.6), respectively. The 12-mo ORR, CRR, and RFR were estimated to be 78% (95% CI: 52.9-91.8), 27.8% (95% CI: 21.3-35.4), and 25.4% (95% CI: 18.2-34.2), respectively. The progression rate was estimated to be 13% (95% CI: 9-18.2). The mean proportion of patients treated with radical cystectomy was estimated to be 24.7 (range 0-85.7). The reported toxicity grades were overall mild, with a median of 3.4% (range 0-33.3%) participants experiencing a dose limiting toxicity. Compared with using radical cystectomy to treat patients failing BCG therapy, at a willingness-to-pay threshold of 100 000 USD, nadofaragene firadenovec was cost effective, with an incremental cost-effectiveness ratio (ICER) of 10 014 USD per quality-adjusted life year (QALY), while nogapendekin alfa inbakicept was less cost effective than nadofaragene firadenovec (ICER of 44 602 USD per QALY). Pembrolizumab, which dominated, was both less costly and more effective than the other strategies. CONCLUSIONS AND CLINICAL IMPLICATIONS: Salvage bladder-sparing therapies show a response rate of around 50% at 3 mo in patients with NMIBC failing BCG. However, long-term data are heterogeneous. Nevertheless, recently developed agents show promising tumor control activity. In the rapidly evolving landscape of urothelial cancer, some of these treatment strategies might be cost effective and improve patients' quality of life. The findings of our review highlight the need for novel, more effective therapeutic strategies. PATIENT SUMMARY: In this study, we reviewed the evidence on the efficacy of bladder-preserving strategies used in patients with bladder cancer recurrence after failing bacillus Calmette-Guérin (BCG) therapy. We found that these strategies show a response rate of around 50% at 3 mo. However, long-term data are heterogeneous. Nevertheless, recently developed agents show promising tumor control activity. In the rapidly evolving landscape of urothelial cancer, some of these treatment strategies might be cost effective and improve patients' quality of life.
- MeSH
- Adjuvants, Immunologic * therapeutic use economics MeSH
- Cost-Benefit Analysis * MeSH
- Administration, Intravesical MeSH
- BCG Vaccine * therapeutic use economics MeSH
- Neoplasm Invasiveness MeSH
- Humans MeSH
- Neoplasm Recurrence, Local MeSH
- Non-Muscle Invasive Bladder Neoplasms MeSH
- Urinary Bladder Neoplasms * drug therapy pathology therapy economics MeSH
- Treatment Failure MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Systematic Review MeSH
Across the globe, significant inequities in brain tumor treatment, care, and support perpetuate. Identifying and addressing these unmet needs in the context of patients' rights is crucial to reducing inequalities and improving outcomes for people living with brain tumors. Brain tumor patient advocacy addresses and influences gaps in healthcare provision, ensuring optimal treatment, care, and support for patients, their caregivers, and families. Therefore, the purpose of this review is to highlight the variety of challenges faced by brain tumor patients, caregivers, and advocates in various parts of the world and set a benchmark for improvements. Twenty-eight leading brain tumor patient/caregiver advocates from 18 countries in Asia Pacific, Sub-Saharan Africa, North America, Eastern Europe, and Western Europe collaborated to explore unmet and met needs in their countries. Virtual meetings were held with the 5 geographic groupings. Through a process of discussion based on a combination of patient advocates' informed expert opinion, published references, a survey (Asia Pacific) and the informal completion of a matrix of challenges by some of the advocacy organizations involved, agreement within the groupings was also reached regarding what rights within The Brain Tumor Patients' Charter of Rights they felt were being met and where there are still gaps. Acknowledging that some rights in The Brain Tumor Patients' Charter of Rights are aspirational, there still remain many areas of the world where even basic patient rights are not yet attainable. Patient advocacy organizations stand ready to help change this to achieve the best possible health and quality of life outcomes for adults and children living with brain tumors.
- Publication type
- Journal Article MeSH
- Review MeSH
WHAT IS KNOWN ON THE SUBJECT: Missed, rationed or unfinished nursing care represents a global problem that jeopardizes the provision of quality and safe care. This phenomenon is frequently observed in adult, paediatric and child healthcare facilities and various care units. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE: The findings of this review contribute valuable information to inform evidence-based practices, foster organizational improvements and ultimately optimize the overall quality of care in psychiatric healthcare settings. In addition, the review illuminates the far-reaching consequences of care on both patient and nurse outcomes, emphasizing the urgent need for tailored strategies to mitigate these effects. WHAT ARE THE IMPLICATIONS FOR PRACTICE: Based on the synthesis of the literature, a thorough and continuous assessment of patient care needs in the physical, psychological and social domains is needed, primarily utilizing standardized instruments designed for psychiatric settings to ensure a comprehensive understanding of unmet needs. Based on identified unmet needs, nurses should develop individualized care plans and tailor interventions to address them. In addition, nurse managers must adopt and implement regular monitoring mechanisms to track the prevalence of unmet care needs and at the same time establish reporting systems that capture the proportion of unmet needs, allowing timely interventions and adjustments to care delivery. Lastly, nurse managers must not only emphasize the importance of ethical care practices and dignity-focused interventions but also educate healthcare providers, especially nurses, on the potential threats to patient dignity arising from unmet care needs. ABSTRACT: INTRODUCTION: Despite frequent observations of unmet care needs in acute care adult settings, there are a limited number of studies that focus on investigating this phenomenon in the psychiatric setting. AIM: To synthesize the existing empirical research on unmet care needs in psychiatric healthcare settings. METHODS: The search was carried out in August 2023 in four scientific databases, PubMed, ProQuest, Web of Science and OVID Nursing, based on their institutional availability. The search produced 1129 studies. The search and retrieval process reflected the recommendations of the Preferred Reporting Items for systematic reviews and meta-analyses. RESULTS: This review included 14 studies investigating unmet care needs in the psychiatric healthcare setting. Unmet care needs included three domains: physical, psychological and social. The analysis of the factors revealed factors related to the characteristics of the organization, nurse and patient. DISCUSSION: The classification of unmet needs provides a comprehensive understanding of the various challenges facing people in psychiatric healthcare settings. IMPLICATION FOR PRACTICE: Identified factors that influence the occurrence of unmet care needs will help prevent the occurrence of unmet care needs and timely assessment. The resolution of needs helps to achieve patient and nurse outcomes, increase the quality of care provided and patient satisfaction in a psychiatric healthcare setting.
- MeSH
- Mental Disorders therapy MeSH
- Humans MeSH
- Psychiatric Nursing * standards MeSH
- Mental Health Services standards MeSH
- Health Services Needs and Demand MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Malobuněčný karcinom plic (small cell lung cancer, SCLC) představuje agresivní malignitu s omezenými pokroky v léčbě včetně nenaplněné potřeby u pacientů s limitovaným stadiem onemocnění (limited stage SCLC, LS SCLC). Standardní terapie zahrnuje konkomitantní chemoradioterapii následovanou profylaktickým ozařováním mozkovny u vhodných pacientů. Přestože konkomitantní chemoradioterapie prokazatelně zlepšuje celkové přežití, míra recidivy zůstává vysoká a dlouhodobá prognóza je nepříznivá. Nové perspektivní přístupy, které mají za cíl prodloužení přežití a snížení rizika relapsu, zahrnují především imunoterapii. Studie fáze III ADRIATIC hodnotila účinnost durvalumabu u pacientů bez progrese po chemoradioterapii. Analýza ukázala, že podání durvalumabu významně prodlužuje celkové přežití a přežití bez progrese onemocnění. Výsledky naznačují, že udržovací imunoterapie by se mohla stát novým standardem léčby LS SCLC. Další výzkumy jsou zaměřeny na optimalizaci dávkování radioterapie, kombinaci léčiv a identifikaci biomarkerů predikujících odpověď na imunoterapii.
Smaii cell lung cancer (SCLC) is an aggressive malignancy with limited treatment advances, including unmet need in patients with limited stage disease (LS SCLC). Standard therapy includes concomitant chemoradiotherapy followed by prophylactic cranial irradiation in appropriate patients. Although concomitant chemoradiotherapy has been shown to improve overall survival, recurrence rates remain high and long-term prognosis unfavorable. New promising approaches to prolong survival and reduce the risk of relapse include immunotherapy in particular. The phase III ADRIATIC trial evaluated the efficacy of durvalumab in patients without progression after chemoradiotherapy. The analysis showed that administration of durvalumab significantly prolonged overall and progression free survival. The results suggest that maintenance immunotherapy could become the new standard of care for LS SCLC. Further research is focused on optimizing radiotherapy dosing, drug combinations, and identifying biomarkers predictive of response to immunotherapy.
Dermatomyositis (DM) is a rare and debilitating, systemic, autoimmune disease. While heterogenous in presentation and severity, DM is primarily characterised by a spectrum of skin and muscle disease, which may include proximal muscle weakness and recalcitrant cutaneous eruptions. DM may also be associated with joint pain and stiffness, inflammatory arthritis, dysphagia, fatigue, and calcinosis. The current standard of care for DM includes glucocorticoids, immunosuppressants, and intravenous immunoglobulin (IVIg). Unfortunately, these medications are not uniformly effective and can lead to adverse events, particularly with chronic use, necessitating discontinuation of therapy. Therefore, a substantial unmet need exists for more tailored and efficacious therapies that target DM pathogenesis. Brepocitinib is an oral, once-daily, novel, and specific TYK2/JAK1 inhibitor. Brepocitinib's potent inhibition of TYK2 and JAK1 reduces the signalling of pro-inflammatory cytokines, including IFN-α/β, IL-12, IL-23, and IFNγ, that have been implicated in the pathogenesis of DM. Other JAK inhibitors have been used off-label in both case series and open-label clinical trials in patients with DM; and brepocitinib has demonstrated efficacy in phase 2 clinical trials of several other autoimmune diseases, including plaque psoriasis, psoriatic arthritis, Crohn's disease, hidradenitis suppurativa, and ulcerative colitis. Therefore, there is a strong scientific and clinical rationale for the utility and potential effectiveness of brepocitinib in the treatment of DM patients. Currently, the safety, tolerability, and efficacy of brepocitinib is being evaluated in the largest (n=225) double-blind placebo-controlled phase 3 trial in DM patients to date (VALOR - NCT0543726).
- MeSH
- Dermatomyositis * drug therapy diagnosis immunology MeSH
- Protein Kinase Inhibitors * therapeutic use adverse effects MeSH
- Janus Kinase 1 * antagonists & inhibitors MeSH
- TYK2 Kinase * antagonists & inhibitors MeSH
- Humans MeSH
- Signal Transduction drug effects MeSH
- Treatment Outcome MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
INTRODUCTION: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) may be as high as 38% in the adult population with potential serious complications, multiple comorbidities and a high socioeconomic burden. However, there is a general lack of awareness and knowledge about MASLD and its progressive stages (metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis). Therefore, MASLD is still far underdiagnosed. The 'Global Research Initiative for Patient Screening on MASH' (GRIPonMASH) consortium focuses on this unmet public health need. GRIPonMASH will help (primary) healthcare providers to implement a patient care pathway, as recommended by multiple scientific societies, to identify patients at risk of severe MASLD and to raise awareness. Furthermore, GRIPonMASH will contribute to a better understanding of the pathophysiology of MASLD and improved identification of diagnostic and prognostic markers to detect individuals at risk. METHODS: This is a prospective multicentre observational study in which 10 000 high-risk patients (type 2 diabetes mellitus, obesity, metabolic syndrome or hypertension) will be screened in 10 European countries using at least two non-invasive tests (Fibrosis-4 index and FibroScan). Blood samples and liver biopsy material will be collected and biobanked, and multiomics analyses will be conducted. ETHICS AND DISSEMINATION: The study will be conducted in compliance with this protocol and applicable national and international regulatory requirements. The study initiation package is submitted at the local level. The study protocol has been approved by local medical ethical committees in all 10 participating countries. Results will be made public and published in scientific, peer-reviewed, international journals and at international conferences. REGISTRATION DETAILS: NCT05651724, registration date: 15 Dec 2022.
- MeSH
- Diabetes Mellitus, Type 2 complications MeSH
- Liver Cirrhosis diagnosis MeSH
- Humans MeSH
- Metabolic Syndrome complications MeSH
- Multicenter Studies as Topic MeSH
- Non-alcoholic Fatty Liver Disease * diagnosis MeSH
- Mass Screening * methods MeSH
- Prospective Studies MeSH
- Research Design MeSH
- Fatty Liver * diagnosis epidemiology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial Protocol MeSH
The development of disease-modifying therapies (DMTs) for the treatment of multiple sclerosis (MS) has been highly successful in recent decades. It is now widely accepted that early initiation of DMTs after disease onset is associated with a better long-term prognosis. However, the question of when and how to de-escalate or discontinue DMTs remains open and critical. This topic was discussed during an international focused workshop organized by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in 2023. The aim was to review the current evidence on the rationale for, and the potential pitfalls of, treatment de-escalation in MS. Several clinical scenarios emerged, mainly driven by a change in the benefit-risk ratio of DMTs over the course of the disease and with ageing. The workshop also addressed the issue of de-escalation by the type of DMT used and in specific situations, including pregnancy and paediatric onset MS. Finally, we provide practical guidelines for selecting appropriate patients, defining de-escalation and monitoring modalities and outlining unmet needs in this field.
BACKGROUND: Despite many efforts to effectively treat PDAC, PDAC carries one of the highest mortality rates of all major cancers. Thus, there is a critical unmet need to develop novel approaches to improve the clinical outcome of PDAC. It is well known that many cancers, including PDAC, generate a local TME that allows cancer to escape normal immune surveillance. Phosphatidylserine (PS), a negatively charged phospholipid that is abundant on the cancer cell membrane and with known actions to promote the secretion of immunomodulatory proteins, may provide a mechanism to regulate the TME. This study explored that possibility. METHODS: MΦ differentiation and polarization were assessed by Western blotting and flow cytometric approaches. PS exposure and surface markers were analyzed by flow cytometry. Protein-protein and protein-lipid interactions were analyzed by immunofluorescence and enzyme-linked immunosorbent assay (ELISA). Phospholipid and SapC-DOPG treatment were employed to assess target protein functions in MΦ polarization, tumor growth, and survival in subcutaneous and orthotopic tumor models. The PK-PD and safety of SapC-DOPG were tested on orthotopic mouse models. RESULTS: Our studies show that PDAC secretes Hsp70 that stimulates the MΦ polarization to the immunosuppressive M2 phenotype. We found that high surface PS on cancer cells correlates with increased secretion of Hsp70 and is associated with higher MΦ differentiation activity in vitro and in vivo. Furthermore, blocking cancer cell-secreted Hsp70 with SapC-DOPG reverses the immune suppression and reduces tumor growth. CONCLUSIONS: These preclinical results reveal a novel immunotherapeutic approach to potentially improve the outcome of PDAC treatment in humans.
- Publication type
- Journal Article MeSH
Substance addiction is a complex mental disorder with significant unmet treatment needs, especially in terms of effective medications. Craving in addiction is closely linked to the interaction between dopamine and glutamate in the brain's reward pathway. Therefore, drugs targeting glutamatergic signaling may have potential for treatment. This review examines the potential of AMPA/kainate glutamatergic receptor antagonists in reducing addictive-like behaviours in experimental rodents. To this end, the text summarizes the behavioural results of preclinical studies on stimulant substances (cocaine, amphetamine, methamphetamine, MDMA), nicotine, opioids (morphine and heroin), and alcohol. These experiments employ various protocols and routes of administration, using different strains of mice and rats. The main behavioural methods used in the research include behavioural sensitization protocols, drug-induced locomotor activity assessments, conditioned behaviours, and operant self-administration models. The reviewed literature demonstrates the benefit of AMPA/kainate antagonists, mainly in the most studied cocaine dependence, and particularly in attenuating cocaine-seeking behaviour via microinjection into the nucleus accumbens core. Regarding other addictive substances, despite some conflicting results, there is a substantial body of literature showing promising outcomes following systemic or intracerebral administration of AMPA/kainate antagonists. The main issue is the variability of the research protocols used across laboratories, including differences in animal species, strains, sex and environmental conditions. Moreover, each addictive substance exhibits distinct mechanisms of action and addiction development, rendering the pursuit of a universal drug for addiction treatment unrealistic. Nevertheless, AMPA/kainate antagonists seem to have potential as a supportive treatment in addiction to cocaine as well as other substances.
- MeSH
- Receptors, AMPA * antagonists & inhibitors MeSH
- Excitatory Amino Acid Antagonists * therapeutic use pharmacology MeSH
- Behavior, Animal * drug effects MeSH
- Humans MeSH
- Behavior, Addictive * drug therapy MeSH
- Substance-Related Disorders * drug therapy metabolism MeSH
- Receptors, Kainic Acid * antagonists & inhibitors MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
