Drop-out, adherence, and compliance in randomized controlled trials of exercise training in multiple sclerosis: Short report.

We documented reporting and rates of drop-out, adherence, and compliance from 40 randomized controlled trials (RCTs) included in our meta-analysis on safety of exercise training (ET) in MS. We adopted definitions and metrics of adherence and compliance provided by the MoXFo adherence group. Drop-out was reported in 100% of the RCTs and approximated 10% for intervention and control conditions. Adherence and compliance were reported in approximately 50% and 10% of the RCTs, respectively, and approximated 80% and 70%, respectively. Standardized metrics for reporting adherence and compliance are important in future RCTs for understanding the impact on outcomes and translation of research evidence into practice.

Attitudes towards COVID-19 vaccination in adults with haematological malignancies.

INTRODUCTION: Despite people with haematological malignancies being particularly vulnerable to severe COVID-19 infection and complications, vaccine hesitancy may be a barrier to optimal vaccination. This study explored attitudes towards COVID-19 vaccination in people with haematological malignancies. METHODS: People with haematological malignancies at nine Australian health services were surveyed between June and October, 2021. Sociodemographic and clinical characteristics were collected. Attitudes towards COVID-19 vaccination were explored using the Oxford COVID-19 Vaccine Hesitancy Scale, the Oxford COVID-19 Vaccine Confidence and Complacency Scale, and the Disease Influenced Vaccine Acceptance Scale-Six. Open-ended comments were qualitatively analysed. RESULTS: A total of 869 people with haematological malignancies (mean age 64.2 years, 43.6% female) participated. Most participants (85.3%) reported that they had received at least one COVID-19 vaccine dose. Participants who were younger, spoke English as a non-dominant language, and had a shorter time since diagnosis were less likely to be vaccinated. Those who were female or spoke English as their non-dominant language reported greater vaccine side-effects concerns. Younger participants reported greater concerns about the vaccine impacting their treatment. CONCLUSION: People with haematological malignancies reported high vaccine uptake, however, targeted education for specific participant groups may address vaccine hesitancy concerns, given the need for COVID-19 vaccine boosters.

Capecitabine-Induced Genital Hand-Foot Syndrome Treated With Topical Tacrolimus.

We describe a rare case of capecitabine-induced palmar-plantar erythrodysesthesia (PPE), or hand-foot syndrome (HFS), involving the genitals, which resolved with tacrolimus therapy, in a patient with cT3dN3 stage IIIc moderately differentiated proximal rectal adenocarcinoma who was undergoing neoadjuvant chemotherapy. Given its severe impact on the quality of life, HFS often requires independent local anti-inflammatory treatment and subsequent dose delay and/or modification of the patient's chemotherapy. We believe that our findings in this report can aid clinicians in the early recognition and management of capecitabine-associated HFS resulting in balanitis, as prompt treatment may reduce morbidity and avoid prolonged interruption of chemotherapy in these patients.

Influence of Income, Education, and Medicaid Expansion on Palliative Care in Acute Myeloid Leukemia Using the National Cancer Database.

Palliative care is integral to symptom management, and we examined its relationship with income, education, and Medicaid expansion in acute myeloid leukemia. This was a retrospective cross-sectional study using the National Cancer Database that included patients with acute myeloid and monocytic leukemias > 18 years of age treated at Commission on Cancer facilities from 2004 to 2016. Univariate and multivariate models were adjusted for demographic variables and facility characteristics. There were 124,988 patients, but only 106,495 had palliative care data, and of this 4111 (3%) received palliative care. The most educated had the highest odds of receiving palliative care (odds ratio, OR 1.23, 95% CI 1.08-1.41; P = 0.002), but the highest income bracket (≥ $63,333) had the lowest odds (OR 0.82, 95% CI 0.72-0.93; P = 0.003). Residence in states with Medicaid expansion (January 2014 onward) had greater palliative care utilization. Palliative care use was associated with higher education but underutilized with higher incomes. Increased access with Medicaid expansion suggests the importance of public insurance.

Early Stage Preclinical Formulation Strategies to Alter the Pharmacokinetic Profile of Two Small Molecule Therapeutics.

Early stage chemical development presents numerous challenges, and achieving a functional balance is a major hurdle, with many early compounds not meeting the clinical requirements for advancement benchmarks due to issues like poor oral bioavailability. There is a need to develop strategies for achieving the desired systemic concentration for these compounds. This will enable further evaluation of the biological response upon a compound-target interaction, providing deeper insight into the postulated biological pathways. Our study elucidates alternative drug delivery paradigms by comparing formulation strategies across oral (PO), intraperitoneal (IP), subcutaneous (SC), and intravenous (IV) routes. While each modality boasts its own set of merits and constraints, it is the drug's formulation that crucially influences its pharmacokinetic (PK) trajectory and the maintenance of its therapeutic levels. Our examination of model compounds G7883 and G6893 highlighted their distinct physio-chemical attributes. By harnessing varied formulation methods, we sought to fine-tune their PK profiles. PK studies showcased G7883's extended half-life using an SC oil formulation, resulting in a 4.5-fold and 2.5-fold enhancement compared with the IP and PO routes, respectively. In contrast, with G6893, we achieved a prolonged systemic coverage time above the desired target concentration through a different approach using an IV infusion pump. These outcomes underscore the need for tailored formulation strategies, which are dictated by the compound's innate properties, to reach the optimal in vivo systemic concentrations. Prioritizing formulation and delivery optimization early on is pivotal for effective systemic uptake, thereby facilitating a deeper understanding of biological pathways and expediting the overall clinical drug development timeline.

Urine cytology in the detection of renal cell carcinomas - a territory-wide multi-institutional retrospective review of more than 2 decades.

INTRODUCTION: Compared with urothelial lesions of the upper urinary tract, the diagnostic performance of urine cytology in detection of renal cell carcinomas is underreported. This study aims to establish the role of urine cytology in the assessment of renal carcinomas by a multi-institute review of urine cytology from nephrectomy confirmed renal cell carcinomas, referenced against renal urothelial and squamous cell carcinomas. METHODS: Records of nephrectomy performed from the 1990s to 2020s at three hospitals were retrieved and matched to urine cytology specimens collected within 1 year prior. Patient demographics, specimen descriptors, and histology and staging parameters were reviewed and compared against cytologic diagnoses. RESULTS: There were 1147 cases of urine cytology matched with renal cell carcinomas, with 666 renal urothelial/squamous carcinomas for comparison. The detection rate for urothelial/squamous (atypia or above [C3+]: 63.1%; suspicious or above [C4+]: 24.0%) were higher than renal cell carcinoma (C3+: 13.1%; C4+: 1.5%) (p < 0.001). The positive rate for upper tract urine exceeded other collection methods at 45.0% (C3+) and 10.0% (C4+) (p < .01). Other factors associated with increased positive rates were male sex, collecting duct carcinoma histology, nuclear grade, and renal/sinus involvement (p < .05). Multivariate analysis revealed additional positive correlations with presence of sarcomatoid tumor cells, lymphovascular invasion, and perinephric fat involvement (p < .05). Larger lesion size and higher urine volume did not improve detection rates (p < .05). CONCLUSIONS: The detection rate of renal cell carcinomas is suboptimal compared with urothelial carcinomas, although urine samples collected from cystoscopy or percutaneous nephrostomy significantly outperformed voided urine specimens.

Case report: An exceptional responder of low-dose continuous 5-FU in a patient with de-novo stage IV triple-negative breast cancer with liver and bone marrow failure.

Continuous low-dose 5-FU was popularized as a therapy for pretreated metastatic breast cancer for the past few decades, spurred by the advent of the electronic infusion pump. Capecitabine, otherwise known by its trade name Xeloda, is a prodrug of 5-fluorouracil (5-FU), which is administered orally in many chemotherapy regimens, and plays a role in metastatic breast cancer treatment refractory to traditional anthracyclines and taxane therapy. In this case presentation, we describe a unique case of refractory de-novo stage IV triple-negative breast cancer presented with right breast primary invasive ductal carcinoma, extensive lymphadenopathy, with biopsy proven bone marrow infiltration, diffuse hepatomegaly, splenomegaly, significant hyperbilirubinemia, and bone marrow failure treated with continuous 5-FU infusion and subsequently oral capecitabine after initial treatment failure with nab-paclitaxel and sacituzimab govitecan. With this case presentation, the authors aim to showcase the versatility of 5-FU and its prodrug in treatment of metastatic triple-negative breast cancer with severe bone marrow and liver involvement while highlighting key physiologic and pharmacologic mechanisms.