Objective: The objectives of this study were to evaluate functional outcomes of cervical motor control, strength and endurance following active transcranial direct current stimulation (tDCS) with exercise therapy (ET) compared to sham tDCS/+ET in patient with cervicogenic headache (CGH), Design: This was a pilot sham-controlled, participant and assessor blinded, randomized controlled trial. Methods: Thirty-two participants with CGH were randomized to active tDCS/+ET or sham tDCS/+ET. Participants completed 6-weeks of daily ET concurrently combined with 3 sessions per week of tDCS. Assessments included: craniocervical flexion test (mmHg), cervical isometric strength (N), cervical flexor and extensor endurance (seconds), and range of motion (degrees) pre-treatment, post-treatment, 6-weeks and 12-weeks post treatment. Linear mixed effect models evaluated group-time interactions at each follow-up while accounting for exercise program adherence and sex. Results: There were significant group-time interactions for activation scores on the craniocervical flexion test from pre-treatment to post-treatment (β = 1.571; 95%CI[0.155, 2.988]; p = 0.030), 6-weeks (β = 1.571; 95%CI[0.155, 2.988]; p = 0.030), and 12-weeks (β = 1.954; 95%CI[0.465, 3.443]; p = 0.011) favoring the active tDCS/+ET group. Conclusions: Active tDCS/+ET demonstrated significant benefits in deep cervical flexor motor control compared to sham tDCS/+ET that remained improved up to 12 weeks post-treatment. This suggests tDCS/+ET may improve of functional outcomes for patients with CGH.

Introduction: Atezolizumab plus bevacizumab (AB) and lenvatinib (LEN) demonstrate non-inferior survival compared with sorafenib for first-line treatment of unresectable hepatocellular carcinoma (HCC) but have not been directly compared. We retrospectively compared survival outcomes between patients treated with AB and LEN in Canada. Methods: We identified patients with unresectable HCC treated with AB or LEN as first-line systemic therapy from 2018 to 2022 at participating cancer centers. Propensity score matching was used to account for clinicopathologic and treatment-related confounders. Three-year progression-free survival (PFS) and overall survival (OS) were compared before and after matching, and Cox regression assessed the association between first-line therapy and survival outcomes. Results: Among 437 eligible patients, 155 received AB and 282 received LEN. Before matching, AB was associated with improved OS (19.7 vs. 14.4 months; HR = 0.75; 95%CI = 0.58–0.88; p = 0.04), but not PFS (8.2 vs. 6.5 months; HR = 0.89; 95%CI = 0.71–1.12; p = 0.32). After matching, 140 AB-treated and 249 LEN-treated patients remained. AB was associated with improved OS (19.7 vs. 15.0 months; HR = 0.75; 95%CI = 0.58–0.88; p = 0.03), while PFS remained similar (8.4 vs. 6.7 months; HR = 0.89; 95%CI = 0.71–1.12; p = 0.32). Conclusions: First-line AB was associated with improved OS compared with LEN, while PFS was similar. These real-world findings support AB as a first-line option when prioritizing survival.

Background Cervicogenic headaches (CGH) are common following concussion and whiplash injuries and significantly reduce patient quality of life. CGH is often associated with neck, jaw and/or facial pain and reduced neck mobility. Conservative therapy and injection-based therapies are cornerstones of treatment for CGH but have shown limited efficacy. Transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) has shown promise in treating other chronic pain and headache conditions. The primary aim of this trial is to evaluate the feasibility and safety of tDCS when combined with conservative therapy for the treatment of CGH. The study will evaluate retention and dropout rates, adherence to the protocol and adverse events. Exploratory aims will investigate the association of CGH and various health outcomes, inclusive of pain intensity, headache frequency and duration, neck mobility, quality of life, pain sensitivity, and medication usage. Methods Forty adults (aged 18–65), blinded to treatment arm, will be randomized into one of two groups: active tDCS with conservative therapy or sham tDCS with conservative therapy. tDCS will be applied over M1 by a trained research assistant three times per week for 6 weeks. Conservative therapy will be provided immediately post-tDCS. The primary outcomes of this trial will be the feasibility and safety of this intervention. Feasibility will be defined as greater than 30% recruitment, greater than 70% protocol adherence, and greater than 70% retention rate. Safety will be defined as no severe adverse events and less than 30% increase in adverse effects. Secondary exploratory outcomes will be assessed using the following: numeric pain rating scale (NPRS), headache impact test-6 (HIT-6), rivermead PPCS questionnaire (RPQ), cranio-cervical flexion test (CCFT), cervical extensor endurance test (CEET), cervical flexor endurance test (CFET), dynamometry neck-strength assessment (DNSA), the European quality of life five dimension (EQ-5D), patient reported outcomes measurement information system (PROMIS) pain interference scale, pain catastrophizing scale (PCS), and section A - quantitative analgesics questionnaire (QAQ-A). Discussion This pilot study will be the first to evaluate the use of tDCS combined with conservative therapy for the treatment of cervicogenic headaches. Trial Registration: ClinicalTrials.gov - NCT05582616 (registered October 4th, 2022) https://clinicaltrials.gov/ct2/show/NCT05582616

Capecitabine plus temozolomide (CAPTEM) improves progression-free survival (PFS) in pancreatic endocrine and neuroendocrine neoplasms (PNENs), yet its real-world effectiveness across other endocrine and neuroendocrine neoplasm (ENEN) subtypes remains uncertain. We conducted a retrospective population-based cohort study including 159 adults with ENENs treated with CAPTEM in Alberta, Canada (2011–2021). Patients were stratified by primary tumor site, treatment line, and number of CAPTEM cycles received. Kaplan–Meier methods and Cox proportional hazards models adjusted for age and sex were used to evaluate PFS and overall survival (OS). Compared with pancreatic neuroendocrine neoplasms PNENs, gastrointestinal neuroendocrine neoplasms (GINENs) demonstrated similar PFS and OS. In contrast, pulmonary neuroendocrine neoplasms (PuNENs) and other ENENs (OENENs) were associated with significantly shorter PFS and OS. Use of CAPTEM in the first-line setting was associated with improved PFS (HR 0.56, 95% CI 0.40–0.78, p < 0.001) and OS (HR 0.42, 95% CI 0.29–0.62, p < 0.001). Receipt of ≥6 treatment cycles was also strongly associated with superior PFS (HR 0.22, 95% CI 0.16–0.32, p < 0.001) and OS (HR 0.22, 95% CI 0.14–0.34, p < 0.001). CAPTEM shows comparable real-world effectiveness in GINENs and PNENs but appears less effective in PuNENs and other OENEN subtypes. Early initiation and adequate treatment duration are key factors associated with improved survival outcomes.