Recurrence Risk Stratification for Women with FIGO Stage I Uterine Endometrioid Carcinoma Who Underwent Surgical Lymph Node Evaluation

Purpose/Objective(s): To estimate the recurrence risk based on the number of prognostic factors in women with FIGO stage I uterine endometrioid carcinoma (EC) in a large cohort of patients who underwent surgical staging including surgical lymph node evaluation (SLNE) and were managed with no adjuvant therapy. Materials/Methods: We queried our in-house prospectively maintained uterine cancer database for patients with FIGO stage I EC underwent surgical staging including SLNE between 1/1990-12/2020. Patients with synchronous ovarian and breast cancer diagnosis were excluded as well as those who received adjuvant therapy of any form. Patient\u27s demographics and pathologic variables were analyzed. We used multivariate analysis (MVA) with Stepwise Model Selection to determine risk factors for 5-year recurrence-free survival (RFS). Study population was then stratified based on the number of risk factors identified (0, 1 or 2). The resultant groups were compared for RFS, disease-specific survival (DSS) and overall survival (OS) using log-rank test and Kaplan-Meier curves. Additionally, independent predictors of DSS and overall OS were estimated. Results: 706 patients were identified who met our inclusion criteria with a median age of 60 years (range, 30-93) and a median follow-up of 120 months. All patients had at least pelvic SLNE with a median number of examined lymph node (LN) of 8 (range, 1-66): 66 patients (11%) had a sentinel LN sampling and 43% had paraaortic SLNE. 639 patients (91%) were stage IA and lymphovascular space invasion (LVSI) was detected in 6% (n=41). Recurrence was diagnosed in 44 patients (6%). Independent predictors of 5-year RFS include age ≥ 60 years (p=0.038), grade 2 vs. 1 (p=0.003), and grade 3 vs 1 (p\u3c0.001). 5-year RFS for group-0 (age \u3c 60 years and grade 1) was 98% vs. 92% for group-1 (either: age ≥ 60 years or grade 2/3) vs 84% for group-2 (both: age ≥ 60 years and grade 2/3), respectively (p\u3c0.001). 5- year DSS for the three groups was (100% vs 98% vs 95%, p=0.012) and 5-year OS was (98% vs 90% vs 81%, p\u3c0.001), respectively. On MVA, stage IB vs IA was deterministic for DSS (p=0.02); whereas age ≥ 60 years (p\u3c0.001) and grade 3 vs grade 1 (p=0.004) were predictors for worse OS. Conclusion: In patients with stage I endometrioid carcinoma who had surgical staging including SLNE and no adjuvant therapy, only age ≥ 60 years and high tumor grade were independent predictors of cancer recurrence and hence can be used to quantify individualized recurrence risk. Surprisingly, LVSI was not an independent prognostic factor in this study cohort with SLNE

The Impact of Human Papillomavirus Educational Intervention Study on the Knowledge, Health Beliefs, Health Behaviors and Increasing the Use of Gardasil in Women of Color

Lack of human papillomavirus (HPV) knowledge and cervical cancer awareness are factors contributing to a disproportion in African American (AA) women with cervical cancer. The purpose of this intervention study was to use gender specific and culturally appropriate HPV educational materials to increase HPV knowledge and cervical cancer awareness, to increase health beliefs, and the intent for AA women to use the HPV vaccine. Convenience sampling was used to describe a sample of 98 AA women recruited from an Ambulatory Women’s health clinic between 2015 and 2017. HPV educational videos and pamphlets materials were used to collect baseline and post intervention knowledge using a self-administered questionnaire, video, and pamphlet. Results revealed an increase in HPV and cervical cancer knowledge, and recommended use of HPV vaccine with family members. HPV educational materials increased women’s knowledge of HPV and cervical cancer, increased healthy behaviors, and the intent to use HPV vaccine with family members, without personal intent to take the HPV vaccine. Future research is needed to examine the decrease in AA women’s’ intent to receive the HPV vaccine

Survival Outcomes and Patterns of Recurrence After Adjuvant Vaginal Cuff Brachytherapy and Chemotherapy in Early-Stage Uterine Serous Carcinoma

Background: Uterine serous carcinoma (USC) is a relatively rare histology that portends a poor prognosis. The optimal adjuvant therapy for early-stage USC remains controversial; however, adjuvant vaginal cuff brachytherapy (VB) and chemotherapy is a commonly utilized strategy. Objectives: We sought to characterize predictors of survival endpoints and determine recurrence patterns in women with early-stage USC who received adjuvant VB and chemotherapy. Methods: We queried our prospectively maintained database for patients with 2009 FIGO stages I-II USC who underwent adequate surgical staging at our institution and received adjuvant chemotherapy with carboplatin and paclitaxel along with VB. We excluded women with synchronous malignancies. Overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were assessed by Kaplan-Meier and log-rank tests. Univariate (UVA) and multivariate analyses (MVA) were performed to identify statistically significant predictors of survival endpoints. Variables with P\u3c0.1 on UVA were included in a MVA and any variable with P\u3c0.05 was considered statistically significant. Results: We identified 77 women who met our inclusion criteria who underwent surgical staging between 1991 and 2018. The median follow-up time was 36 months (range 6-125). The median age was 66 years. Of the cohort, 70% were FIGO stage IA, 17% were stage IB, and 13% were stage II. The median number of dissected lymph nodes (LN) was 22. There were 10 women (13%) diagnosed with a recurrence with a median time to recurrence of 12.0 months. The main site of initial recurrence was distant in seven patients (70%) with the remaining recurrences being pelvic/para-aortic. The 5-year RFS for patients who experienced a distant recurrence was 87% (95% Confidence Interval [CI] 0.75-0.94). For the entire cohort, 5-year OS, DSS, and RFS were 83% (95% CI 0.68-0.91), 92% (95% CI 0.78-0.97), and 83% (95% CI 0.71-0.91), respectively. The sole predictor of 5-year OS on UVA was receipt of omentectomy (P=0.09). The predictors of 5-year DSS on UVA were presence of positive peritoneal cytology (P=0.03), number of LN examined (Hazard Ratio [HR] 1.10, 95% CI 1.00-1.21, P=0.05), and number of para-aortic LN examined (HR 1.16 [95% CI 1.01-1.32], P=0.03). The sole independent predictor of DSS was the presence of positive peritoneal cytology (HR 0.03 [95% CI 0.00-0.72], P=0.03). Predictors of five-year RFS on UVA were robotic vs open surgery technique (P=0.06), presence of positive peritoneal cytology (P=0.01), percent myometrial invasion (HR 5.59 [95% CI 0.84-37.46], P=0.08), and presence of lymphovascular space invasion (LVSI) (P=0.05). Conclusions: Five-year survival outcomes were promising in this cohort of women with early-stage USC treated with adjuvant chemotherapy and VB; however, this study shows that the predominant pattern of relapse in this population is distant, suggesting the need to optimize systemic therapy. Possible predictors of worse outcomes include positive peritoneal cytology, deep myometrial invasion, and presence of LVSI. Multi-institutional pooled analyses are warranted to confirm our study results

Conceptualising the empowerment of caregivers raising children with developmental disabilities in Ethiopia:a qualitative study

BACKGROUND: Caregivers of children with developmental disabilities (DDs) in Ethiopia experience stigma and exclusion. Due to limited existing services and substantial barriers to accessing care, they often lack support. Caregiver empowerment could help address injustices that hinder their capacity to support their child as they would like. The aim of this study was to explore the meaning and potential role of empowerment for caregivers raising a child with a DD and how empowerment was situated in relation to other priorities in service development.METHODS: This was a qualitative phenomenological study. Semi-structured interviews were conducted in Amharic and English with caregivers of children with a DD (n = 15), clinicians (n = 11), community-based health extension workers (n = 5), representatives of non-governmental organisations working with families with DDs (n = 17), and representatives of local authorities in health, education, and social care (n = 15). Data were analysed thematically.RESULTS: Three main themes were developed: "Barriers to exercising caregivers' agency"; "Whose decision is it to initiate empowerment?"; and "Supporting caregivers through support groups". Caregiver capacity to do what they thought was best for their child was undermined by poverty, a sense of hopelessness, experience of domestic abuse and multiple burdens experienced by those who were single mothers. Caregivers were nonetheless active in seeking to bring about change for their children. Caregivers and professionals considered support groups to be instrumental in facilitating empowerment. Participants reflected that caregiver-focused interventions could contribute to increasing caregivers' capacity to exercise their agency. A tension existed between a focus on individualistic notions of empowerment from some professionals compared to a focus on recognising expertise by experience identified as vital by caregivers. Power dynamics in the context of external funding of empowerment programmes could paradoxically disempower.CONCLUSION: Caregivers of children with DDs in Ethiopia are disempowered through poverty, stigma, and poor access to information and resources. Shifting power to caregivers and increasing their access to opportunities should be done on their own terms and in response to their prioritised needs

Conceptualising the empowerment of caregivers raising children with developmental disabilities in Ethiopia: a qualitative study

Background Caregivers of children with developmental disabilities (DDs) in Ethiopia experience stigma and exclusion. Due to limited existing services and substantial barriers to accessing care, they often lack support. Caregiver empowerment could help address injustices that hinder their capacity to support their child as they would like. The aim of this study was to explore the meaning and potential role of empowerment for caregivers raising a child with a DD and how empowerment was situated in relation to other priorities in service development. Methods This was a qualitative phenomenological study. Semi-structured interviews were conducted in Amharic and English with caregivers of children with a DD (n = 15), clinicians (n = 11), community-based health extension workers (n = 5), representatives of non-governmental organisations working with families with DDs (n = 17), and representatives of local authorities in health, education, and social care (n = 15). Data were analysed thematically. Results Three main themes were developed: “Barriers to exercising caregivers’ agency”; “Whose decision is it to initiate empowerment?”; and “Supporting caregivers through support groups”. Caregiver capacity to do what they thought was best for their child was undermined by poverty, a sense of hopelessness, experience of domestic abuse and multiple burdens experienced by those who were single mothers. Caregivers were nonetheless active in seeking to bring about change for their children. Caregivers and professionals considered support groups to be instrumental in facilitating empowerment. Participants reflected that caregiver-focused interventions could contribute to increasing caregivers’ capacity to exercise their agency. A tension existed between a focus on individualistic notions of empowerment from some professionals compared to a focus on recognising expertise by experience identified as vital by caregivers. Power dynamics in the context of external funding of empowerment programmes could paradoxically disempower. Conclusion Caregivers of children with DDs in Ethiopia are disempowered through poverty, stigma, and poor access to information and resources. Shifting power to caregivers and increasing their access to opportunities should be done on their own terms and in response to their prioritised needs

Amplifying the Heat Shock Response Ameliorates ALS and FTD Pathology in Mouse and Human Models

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are now known as parts of a disease spectrum with common pathological features and genetic causes. However, as both conditions are clinically heterogeneous, patient groups may be phenotypically similar but pathogenically and genetically variable. Despite numerous clinical trials, there remains no effective therapy for these conditions, which, in part, may be due to challenges of therapy development in a heterogeneous patient population. Disruption to protein homeostasis is a key feature of different forms of ALS and FTD. Targeting the endogenous protein chaperone system, the heat shock response (HSR) may, therefore, be a potential therapeutic approach. We conducted a preclinical study of a known pharmacological amplifier of the HSR, called arimoclomol, in mice with a mutation in valosin-containing protein (VCP) which causes both ALS and FTD in patients. We demonstrate that amplification of the HSR ameliorates the ALS/FTD-like phenotype in the spinal cord and brain of mutant VCP mice and prevents neuronal loss, replicating our earlier findings in the SOD1 mouse model of ALS. Moreover, in human cell models, we demonstrate improvements in pathology upon arimoclomol treatment in mutant VCP patient fibroblasts and iPSC-derived motor neurons. Our findings suggest that targeting of the HSR may have therapeutic potential, not only in non-SOD1 ALS, but also for the treatment of FTD

Risk Factors and Incidence of Macular Edema after Cataract Surgery:A Database Study of 81984 Eyes

PurposeTo define the incidence of pseudophakic macular edema (PME) after cataract surgery and to identify contributory risk factors.DesignRetrospective database study of electronic medical records (EMRs).ParticipantsA total of 81984 eyes undergoing cataract surgery between December 2010 and December 2014 from 8 independent United Kingdom clinical sites.MethodsStructured clinical data mandated by the EMR were anonymized and extracted for each eye undergoing cataract surgery including: perioperative visual acuity, copathologic features, simultaneous surgical procedures, and the presence or absence of a specified list of intraoperative complications. Diabetic status with matched Early Treatment Diabetic Retinopathy Study (ETDRS) grading also was mandated by the EMR. Eyes receiving prophylactic nonsteroidal anti-inflammatory drugs were excluded.Main Outcome MeasureDiagnosis of cystoid macular edema or new-onset macular edema in patients with diabetes, recorded by a healthcare professional within 90 days of surgery.ResultsBaseline incidence of PME in eyes without operative complications, diabetes, or risk factors was 1.17%. Eyes in which PME developed were more likely to be male, older, and to demonstrate risk factors. The relative risk (RR) was increased in eyes with capsule rupture with or without vitreous loss (RR, 2.61; 95% confidence interval [CI], 1.57–4.34), a previous diagnosis of epiretinal membrane (RR, 5.60; 95% CI, 3.45–9.07), uveitis (RR, 2.88; 95% CI, 1.50–5.51), retinal vein occlusion (RR, 4.47; 95% CI, 2.56–5.92), or retinal detachment repair (RR, 3.93; 95% CI, 2.60–5.92). High myopia, age-related macular degeneration, or prostaglandin analog use were not shown to increase risk. Eyes with PME on average had poorer postoperative visual acuity, which persisted to the latest time point assessed, up to 24 weeks. Eyes from patients with diabetes, even in the absence of retinopathy, had an increased RR (RR, 1.80; 95% CI, 1.36–2.36) of new macular edema after surgery. The risk was higher in the presence of any diabetic retinopathy (DR; RR, 6.23; 95% CI, 5.12–7.58) and rose proportionately with increasing severity of DR.ConclusionsPseudophakic macular edema occurs commonly after phacoemulsification cataract surgery, even in the absence of complications and risk factors. This large retrospective study using structured EMR data quantified the RRs of PME and the risk with increasing ETDRS severity of DR. It highlights the need for prophylactic therapy, especially in those groups of eyes with the highest RRs

Put you in the problem:effects of self-pronouns on mathematical problem solving

Self-cues such as personal pronouns are known to elicit processing biases, such as attention capture and prioritisation in working memory. This may impact the performance of tasks that have a high attentional load like mathematical problem-solving. Here, we compared the speed and accuracy with which children solved numerical problems that included either the self-cue “you,” or a different character name. First, we piloted a self-referencing manipulation with N = 52, 7 to 11 year-olds, testing performance on addition and subtraction problems that had either a single referent (“You”/“Sam”) or more than one referent. We took into account operation and positioning of the pronoun and also measured performance on attention and working memory tasks. We found a robust accuracy advantage for problems that included “you,” regardless of how many characters were included. The accuracy advantage for problems with a self-pronoun was not statistically associated with individual differences in attention or working memory. In our main study (9 to 11 year-olds, N = 144), we manipulated problem difficulty by creating consistently and inconsistently worded addition and subtraction problems. We found significantly higher speed and accuracy for problems that included “you.” However, this effect varied by task difficulty, with the self-pronoun effect being strongest in the most difficult inconsistently worded, subtraction problems. The advantage of problems with a self-pronoun was not associated with individual differences in working memory. These findings suggest that self-cues like the pronoun “you” can be usefully applied in numerical processing tasks, an effect that may be attributable to the effects of self-cues on attention.</p