Chronic low back pain (LBP) is very common, resulting in functional deficits and significant socio-economic burden. Non-pharmacological treatments, such as physical-psychological therapy, are frequently utilized. Vojta therapy (VT) is a type of physical therapy that effectively enhances the automatic control of body posture. This study aimed to evaluate the effects of combining VT with the usual standard of care (USC) therapy on psychometric and functional parameters in patients with chronic LBP. A total of 148 patients diagnosed with chronic LBP were recruited and randomized into two groups: LBP-VT (n = 82) and LBP-USC (n = 66). Patients were assessed for demographic characteristics, comorbid conditions, clinical findings, health status, pain symptom scales, psychometric, and functional parameters. The LBP-VT group received VT in addition to USC and electrotherapy, while the LBP-USC group received only USC. Initial Hamilton Depression Scale assessments indicated moderate depression, which improved to mild depression post-treatment. The effect of the treatment on self-esteem was significant for the LBP-VT group and moderate for the LBP-USC group. Functional parameters improved in both groups, with the LBP-VT group having significantly better results. Combining VT with standard care, electrotherapy, and massage significantly improved posture, reduced depression associated with functional deficits, and enhanced self-esteem in patients with chronic LBP.

Immunotherapy has drastically changed the treatment of lung cancer not only in systemic disease but also in the perioperative setting in locally advanced non-small cell lung cancer. In particular, the neoadjuvant and perioperative therapy regimes of the CheckMate 816 and KEYNOTE-671 studies as well as the adjuvant therapy according to the IMPower010 and the PEARLS/KEYNOTE-091 protocols have already been approved by the European Medicines Agency (EMA) for the treatment of selected cases. Other therapy protocols and combination therapies with varying drug classes and therapy modalities are currently being examined for their effectiveness and tolerance. The new treatment landscape creates new opportunities but also challenges for the treating disciplines. This article will focus on the current evidence for perioperative immunotherapy for resectable lung cancer and the resulting therapy standards, especially with regard to patient selection for both neoadjuvant and adjuvant immunotherapy, as well as current research efforts.
Die Einführung der Immuntherapie hat die Behandlung des Lungenkarzinoms drastisch verändert, wobei auch die perioperative Applikation bei lokal fortgeschrittenen nicht kleinzelligen Lungenkarzinomen ermutigende Ergebnisse gezeigt hat. Die neoadjuvanten und perioperativen Therapieregime der CheckMate-816- und KEYNOTE-671-Studie sowie die adjuvanten Therapien nach dem IMPower010- und dem PEARLS/KEYNOTE-091-Protokoll wurden bereits von der Europäischen Arzneimittel-Agentur (EMA) für die Behandlung ausgewählter Fälle zugelassen. Weitere Therapieregime und Kombinationstherapien mit unterschiedlichen Wirkstoffgruppen und Therapiemodalitäten werden derzeit auf ihre Wirksamkeit und Verträglichkeit überprüft. Aus der veränderten Therapielandschaft ergeben sich neue Möglichkeiten, aber auch Herausforderungen für die behandelnden Disziplinen. Die aktuelle Studienlage zur perioperativen Immuntherapie des resektablen Lungenkarzinoms und die sich daraus ergebenden Handlungsempfehlungen, insbesondere bez. der Patientenselektion sowohl für eine neoadjuvante als auch adjuvante Immuntherapie sowie die derzeitigen Forschungsbemühungen werden in diesem Artikel beleuchtet.

Glioblastoma (GBM) presents a significant public health challenge as the deadliest and most common malignant brain tumor in adults. Despite standard-of-care treatment, which includes surgery, radiation, and chemotherapy, mortality rates are high, underscoring the critical need for advancing GBM therapy. Over the past two decades, numerous clinical trials have been performed, yet only a small fraction demonstrated a benefit, raising concerns about the predictability of current preclinical models. Traditionally, preclinical studies utilize treatment-naïve tumors, failing to model the clinical scenario where patients undergo standard-of-care treatment prior to recurrence. Recurrent GBM generally exhibits distinct molecular alterations influenced by treatment selection pressures. In this review, we discuss the impact of treatment-surgery, radiation, and chemotherapy-on GBM. We also provide a summary of treatments used in preclinical models, advocating for their integration to enhance the translation of novel strategies to improve therapeutic outcomes in GBM.

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In the article \"Principled Conscientious Provision: Referral Symmetry and Its Implications for Protecting Secular Conscience,\" Abram L. Brummett, Tanner Hafen, and Mark C. Navin reject what they call the \"referral asymmetry\" in U.S. conscientious objection law in medicine, which recognizes rights of conscientiously objecting physicians to withhold referrals for medical interventions but does not (yet) recognize rights of physicians to make referrals for medical interventions to which they are morally committed but to which their health care institutions are morally opposed. This commentary concentrates on a second asymmetry, namely, the relationship of a health care provider\'s referral or nonreferral to the medical standard of care. The commentary argues that this second asymmetry seems to require action more appropriately recognized as civil disobedience than conscientious provision of referral.

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BACKGROUND: Poverty, HIV and perinatal depression represent a triple threat to public health in sub-Saharan Africa because of their combined negative effects on parenting and child development. In the resource-constrained context of low-income and middle-income countries, a lay-counsellor-delivered intervention that combines a psychological and parenting intervention could offer the potential to mitigate the consequences of perinatal depression while also optimising scarce resources for healthcare.Measuring the cost-effectiveness of such a novel intervention will help decision-makers to better understand the relative costs and effects associated with replicating the intervention, thereby supporting evidence-based decision-making. This protocol sets out the methodological framework for analysing the cost-effectiveness of a cluster randomised controlled trial (RCT) that compares a combined intervention to enhanced standard of care when treating depressed, HIV-positive pregnant women and their infants in rural South Africa.
METHODS: This cost-effectiveness analysis (CEA) protocol complies with the Consolidated Health Economic Evaluation Reporting Standards 2022 checklist. A societal perspective will be chosen.The proposed methods will determine the cost and efficiency of implementing the intervention as per the randomised control trial protocol, as well as the cost of replicating the intervention in a non-research setting. The costs will be calculated using an appropriately adjusted version of the Standardised Early Childhood Development Costing Tool.Primary health outcomes will be used in combination with costs to determine the cost per improvement in maternal perinatal depression at 12 months postnatal and the cost per improvement in child cognitive development at 24 months of age. To facilitate priority setting, the incremental cost-effectiveness ratios for improvements in child cognitive development will be ranked against six other child cognitive-development interventions according to Verguet et al\'s methodology (2022).A combination of activity-based and ingredient-based costing approaches will be used to identify, measure and value activities and inputs for all alternatives. Outcomes data will be sourced from the RCT team.
BACKGROUND: The University of Oxford is the sponsor of the CEA. Ethics approval has been obtained from the Human Sciences Research Council (HSRC, #REC 5/23/08/17), South Africa and the Oxford Tropical Research Ethics Committee (OxTREC #31-17), UK.Consent for publication is not applicable since no participant data are used in this protocol.We plan to disseminate the CEA results to key policymakers and researchers in the form of a policy brief, meetings and academic papers.
UNASSIGNED: ISRCTN registry #11 284 870 (14/11/2017) and SANCTR DOH-27-102020-9097 (17/11/2017).

BACKGROUND: Skin cancer incidence increases globally, requiring effective preventive measures and evidence-based treatment strategies. Current guidelines advocate for surgical excision as a first-line treatment for most early skin cancers. The study investigated practices regarding changing scalpel blades when excising multiple skin lesions in the same patient during the same visit (CSB) and explored how beliefs about iatrogenic seeding influence individual norms of practice.
METHODS: A multidisciplinary survey was conducted among 173 medical specialists involved in skin cancer care. Participants provided demographic information, years of experience, and practices regarding CSB in four clinical scenarios (first excised tumor: basal cell carcinoma, squamous cell carcinoma, melanoma suspect, and evident melanoma). Practice variations based on specialty, experience, and beliefs about seeding risk were statistically assessed.
RESULTS: Surgeons exhibited a significantly higher tendency to change blades compared to non-surgeons across all diagnoses. Iatrogenic seeding (56.52%) and clinical training (18.84%) were the main reasons provided for CSB. Beliefs about seeding risk did not differ significantly between specialties.
CONCLUSIONS: Although the practice of CSB lacks strong scientific rationale, the approach to this practice significantly varies among different medical specialties. Healthcare professionals should critically evaluate and standardize evidence-based practices to ensure optimal patient care and mitigate potential harm.

BACKGROUND: Elevated microRNA-155 (miR-155) expression in non-small-cell lung cancer (NSCLC) promotes cisplatin resistance and negatively impacts treatment outcomes. However, miR-155 can also boost anti-tumor immunity by suppressing PD-L1 expression. Therapeutic targeting of miR-155 through its antagonist, anti-miR-155, has proven challenging due to its dual molecular effects.
METHODS: We developed a multiscale mechanistic model, calibrated with in vivo data and then extrapolated to humans, to investigate the therapeutic effects of nanoparticle-delivered anti-miR-155 in NSCLC, alone or in combination with standard-of-care drugs.
RESULTS: Model simulations and analyses of the clinical scenario revealed that monotherapy with anti-miR-155 at a dose of 2.5 mg/kg administered once every three weeks has substantial anti-cancer activity. It led to a median progression-free survival (PFS) of 6.7 months, which compared favorably to cisplatin and immune checkpoint inhibitors. Further, we explored the combinations of anti-miR-155 with standard-of-care drugs, and found strongly synergistic two- and three-drug combinations. A three-drug combination of anti-miR-155, cisplatin, and pembrolizumab resulted in a median PFS of 13.1 months, while a two-drug combination of anti-miR-155 and cisplatin resulted in a median PFS of 11.3 months, which emerged as a more practical option due to its simple design and cost-effectiveness. Our analyses also provided valuable insights into unfavorable dose ratios for drug combinations, highlighting the need for optimizing dose regimens to prevent antagonistic effects.
CONCLUSIONS: This work bridges the gap between preclinical development and clinical translation of anti-miR-155 and unravels the potential of anti-miR-155 combination therapies in NSCLC.

UNASSIGNED: Inconsistent results observed in recent phase III trials assessing chimeric antigenic receptor T (CAR-T) cell therapy as a second-line treatment compared to standard of care (SOC) in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) prompted a meta-analysis to assess the effectiveness of CAR-T cell therapy in this setting.
UNASSIGNED: Random-effects meta-analysis was conducted to pool effect estimates for comparison between CAR-T cell therapy and SOC. Mixed treatment comparisons were made using a frequentist network meta-analysis approach.
UNASSIGNED: Meta-analysis of three trials with 865 patients showed significant improvement in event-free survival (EFS: HR: 0.51; 95% CI: 0.27-0.97; I2: 92%), progression-free survival (PFS: HR: 0.47; 95% CI: 0.37-0.60; I2: 0%) with CAR-T cell therapy compared to SOC. Although there was a signal of potential overall survival (OS) improvement with CAR-T cell therapy, the difference was not statistically significant between the two groups (HR 0.76; 95% CI: 0.56 to 1.03; I2: 29%). Mixed treatment comparisons showed significant EFS benefit with liso-cel (HR: 0.37; 95% CI: 0.22-0.61) and axi-cel (HR: 0.42; 95% CI: 0.29-0.61) compared to tisa-cel.
UNASSIGNED: CAR-T cell therapy, as a second-line treatment, appears to be effective in achieving higher response rates and delaying the disease progression compared to SOC in R/R DLBCL.