Glioblastoma, the deadliest form of primary brain tumor, remains a disease without cure. Treatment resistance is in large part attributed to limitations in the delivery and distribution of therapeutic agents. Over the last 20 years, numerous preclinical studies have demonstrated the feasibility and efficacy of stem cells as antiglioma agents, leading to the development of trials to test these therapies in the clinic. In this review we present and analyze these studies, discuss mechanisms underlying their beneficial effect and highlight experimental progress, limitations and the emergence of promising new therapeutic avenues. We hope to increase awareness of the advantages brought by stem cells for the treatment of glioblastoma and inspire further studies that will lead to accelerated implementation of effective therapies.
SDB mediates the relationship between fitness and depression, and SDB and depression separately mediate the relationship between fitness and the attention component of cognition.
Introduction CONTACT is a national multidisciplinary study assessing the impact of the COVID-19 pandemic upon diagnostic and treatment pathways among patients with pancreatic ductal adenocarcinoma (PDAC). Methods The treatment of consecutive patients with newly diagnosed PDAC from a pre-COVID-19 pandemic cohort (07/01/2019-03/03/2019) were compared to a cohort diagnosed during the first wave of the UK pandemic (‘COVID’ cohort, 16/03/2020-10/05/2020), with 12-month follow-up. Results Among 984 patients (pre-COVID: n = 483, COVID: n = 501), the COVID cohort was less likely to receive staging investigations other than CT scanning (29.5% vs. 37.2%, p = 0.010). Among patients treated with curative intent, there was a reduction in the proportion of patients recommended surgery (54.5% vs. 76.6%, p = 0.001) and increase in the proportion recommended upfront chemotherapy (45.5% vs. 23.4%, p = 0.002). Among patients on a non-curative pathway, fewer patients were recommended (47.4% vs. 57.3%, p = 0.004) or received palliative anti-cancer therapy (20.5% vs. 26.5%, p = 0.045). Ultimately, fewer patients in the COVID cohort underwent surgical resection (6.4% vs. 9.3%, p = 0.036), whilst more patients received no anti-cancer treatment (69.3% vs. 59.2% p = 0.009). Despite these differences, there was no difference in median overall survival between the COVID and pre-COVID cohorts, (3.5 (IQR 2.8–4.1) vs. 4.4 (IQR 3.6–5.2) months, p = 0.093). Conclusion Pathways for patients with PDAC were significantly disrupted during the first wave of the COVID-19 pandemic, with fewer patients receiving standard treatments. However, no significant impact on survival was discerned.
ObjectivesCognitive-behavioral therapy and pharmacotherapy are effective insomnia treatments, yet half of patients do not remit. Emerging evidence indicates refractory cognitive arousal is associated with poor insomnia treatment outcomes, giving rise to the concept that therapeutic approaches directly aimed at reducing cognitive arousal may benefit patients with a history of inadequate response to intervention. This proof-of-concept study examined the effects of mindfulness-based therapy for insomnia (MBTI) delivered individually via telemedicine on insomnia, depression, and cognitive arousal in patients with treatment-resistant insomnia.MethodsA single-arm trial wherein 19 patients whose insomnia did not remit with prior psychotherapy and/or pharmacotherapy received a course of MBTI as second-stage therapy, which included eight weekly 1-h sessions in an individual format via telemedicine video. Study outcomes included the 15-item version of the five-facet mindfulness questionnaire (FFMQ-15), insomnia severity index (ISI), Patient Health Questionnaire-9 to assess depression (PHQ-9), and three cognitive arousal indices: pre-sleep arousal scale's cognitive factor, perseverative thinking questionnaire, and the daytime insomnia symptom response scale.ResultsPatients reported increased mindfulness from pretreatment to posttreatment (FFMQ-15: 52.95 ± 8.30 to 57.47 ± 9.82, p = 0.008). Patients also reported large reductions in ISI (16.42 ± 3.95 to 8.37 ± 4.19, p < 0.001, Cohen's dz = 1.73; 57.9% remission), PHQ-9 (6.42 ± 3.47 to 3.32 ± 2.93, p = 0.001, Cohen's dz = 0.93), and all cognitive arousal indices (Cohen's dzs = 0.82–1.30) at posttreatment. Six months later, ISI scores and cognitive arousal levels remained significantly lower than pretreatment, although effect sizes decreased for ISI (Cohen's dz = 1.11) and cognitive arousal (Cohen's dzs = 0.63–0.68). Antidepressant effects were no longer significant at follow-up.ConclusionTreatment-resistant insomnia patients are engaged in MBTI, which produces large acute reductions in insomnia, depression, and cognitive arousal. MBTI effects on insomnia and cognitive arousal were moderate to large 6 months after treatment. These findings support the concept and feasibility of MBTI for treatment-resistant patients along with indication that longer-term strategies are needed to help maintain acute treatment gains.Clinical trial registrationClinicalTrials.gov, identifier NCT03724305.
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