Impact of context specificity on response to the shortened WOMAC function scale in patients undergoing total knee arthroplasty.

OBJECTIVE: To determine, in patients undergoing total knee arthroplasty (TKA), whether increasing context specificity of selected items of the shortened version of the Western Ontario and McMaster Universities Osteoarthritis Index function (WOMAC-F) scale (ShortMAC-F) (i) enhanced the convergent validity of the ShortMAC-F with performance-based mobility measures and (ii) impacted on mean scale score, structural validity, reliability, and interpretability. DESIGN: Secondary analysis of randomized clinical trial data. SETTING AND PARTICIPANTS: Patients undergoing TKA (n=114). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The ShortMAC-F was modified by specifying the "ascending stairs" and "rising from sitting" items to enquire about difficulty in performing the tasks without reliance on compensatory strategies, while the modified "level walking" item enquired about difficulty in walking 400 meters. Before and 12 weeks after TKA, patients completed the WOMAC-F, modified ShortMAC-F, knee pain scale, sit-to-stand test, fast gait speed test, and stair-climb test. Interpretability was evaluated by calculating anchor-based substantial clinical benefit (SCB) estimates. RESULTS: The modified ShortMAC-F correlated significantly more strongly than ShortMAC-F or WOMAC-F with pooled performance measures (differences in correlation values, 0.12-0.14). Increasing item context specificity of the ShortMAC-F did not influence its psychometric properties of unidimensionality (comparative fit and Tucker-Lewis indices >0.95; root mean square error of approximation, 0.05-0.08), reliability (Cronbach alpha, 0.75-0.83), correlation with pain intensity (correlation values, 0.48-0.52), and SCB estimates (16 percentage points); however, it resulted in lower mean score (4.5-4.8 points lower). CONCLUSIONS: The modified ShortMAC-F showed sufficient measurement properties for clinical application, and it seemed more adept than WOMAC-F at correlating with performance-based measures in TKA.

Targeting Senescence as a Therapeutic Opportunity for Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is associated with an elevated risk of recurrence and poor prognosis. Historically, only chemotherapy was available as systemic treatment, but immunotherapy and targeted therapies currently offer prolonged benefits. TNBC is a group of diseases with heterogeneous treatment sensitivity, and resistance is inevitable and early for a large proportion of the intrinsic subtypes. Although senescence induction by anticancer therapy offers an immediate favorable clinical outcome once the rate of tumor progression reduces, these cells are commonly dysfunctional and metabolically active, culminating in treatment-resistant repopulation associated with worse prognosis. This heterogeneous response can also occur without therapeutic pressure in response to damage or oncogenic stress, playing a relevant role in the carcinogenesis. Remarkably, there is preclinical and exploratory clinical evidence to support a relevant role of senescence in treatment resistance. Therefore, targeting senescent cells has been a scientific effort in many malignant tumors using a variety of targets and strategies, including increasing proapoptotic and decreasing antiapoptotic stimuli. Despite promising results, there are some challenges to applying this technology, including the best schedule of combination, assessment of senescence, specific vulnerabilities, and the best clinical scenarios. This review provides an overview of senescence in TNBC with a focus on future-proofing senotherapy strategies.

Impact of enhanced personal protective equipment on colonoscopy performance during the COVID-19 pandemic.

Background and study aims Using personal protective equipment (PPE) can reduce risk of disease transmission. During the COVID-19 pandemic, enhanced PPE (EPPE) is recommended when performing endoscopy. We aimed to evaluate the impact of EPPE on colonoscopy performance when compared to standard PPE (SPPE). Patients and methods A review of electronic medical records and endoscopy reports of consecutive patients who underwent colonoscopy during two similar one-month time periods (in 2019 and during the COVID-19 pandemic in 2020) was performed. SPPE was used in 2019 and EPPE was used in 2020. Patient clinical data and procedure-related information were captured and analyzed. The primary outcomes were time to cecum (TTC) and total procedure time. Secondary outcomes were adenoma detection rate (ADR), polyp detection rate (PDR) and cecal intubation rate (CIR). Statistical analysis was performed using STATA v16.1. Results Two hundred and forty-seven colonoscopy procedures were analyzed. Baseline demographics and indications for colonoscopy of patients in both groups were similar. There were no significant differences in median TTC (10.0 vs 10.0 min, P  = 0.524) or total procedure time (22.5 vs 23.0 min, P  = 0.946) between colonoscopy performed in SPPE and EPPE. The ADR, PDR and CIR were also similar. Conclusion Our findings suggest that use of EPPE does not affect colonoscopy performance.

Association between citalopram, escitalopram and QTc prolongation in a real-world geriatric setting.

BACKGROUND: Although the US Food and Drug Administration (FDA) recommended upper limits for citalopram dosing in older adults due to risk of corrected-QT (QTc) prolongation, which was adopted, and extended to escitalopram by Health Canada, the scientific basis is unclear. The objective of this study was to assess the relationship between citalopram/escitalopram dosages and QTc interval in a real-world geriatric setting. METHODS: We reviewed electronic health records at a university-affiliated geriatric health care center, over a 7-year period, to identify patients prescribed citalopram and escitalopram, who had an ECG within 90 days of initiation or dosage change. Linear regression analyses were conducted to assess the relationship between antidepressant dosage and QTc interval. RESULTS: 137 patients were identified (citalopram=97, escitalopram=40). No association was found between citalopram, escitalopram and QTc, in unadjusted or adjusted analyses. Among covariates, older age was significantly associated with QTc prolongation in the escitalopram group. LIMITATIONS: Limitations to the current study include its retrospective design and the small sample size. CONCLUSIONS: These data do not support the FDA or Health Canada's recommended maximum dosages of citalopram or escitalopram in the elderly. Therefore, for patients already on higher doses of these medications, the risk of QTc prolongation may not always outweigh the risk of dose lowering, such as relapse. Until larger prospective studies become available, the decision to comply or not with these federal agencies' recommendations should be weighed on an individual basis, taking into consideration all potential risk factors.

Hepatitis B Virus X Protein and Hepatocarcinogenesis.

Chronic hepatitis B virus (HBV) infection is one of the most associated factors in hepatocarcinogenesis. HBV is able to integrate into the host genome and encode the multi-functional hepatitis B virus x protein (HBx). Although the mechanism between HBx and carcinogenesis is still elusive, recent studies have shown that HBx was able to influence various signaling pathways, as well as epigenetic and genetic processes. This review will examine and summarize recent literature about HBx's role in these various processes.