Association Between Social Determinants of Health and Cancer Treatment Delay in an Urban Population.

PURPOSE: Delays in oncologic time to treatment initiation (TTI) independently and adversely affect disease-specific mortality. Social Determinants of Health (SDoH) are increasingly recognized as significant contributors to patients' disease management and health outcomes. Our academic center has validated a 10-item SDoH screener, and we elucidated which specific needs may be predictive of delayed TTI. METHODS: This is a retrospective cohort study at an urban academic center of patients with a SDoH screening and diagnosis of breast, colorectal, endocrine/neuroendocrine, GI, genitourinary, gynecologic, head and neck, hematologic, hepatobiliary, lung, or pancreatic cancer from 2018 to 2022. Variables of interest included household income, tumor stage, and emergency department (ED) or inpatient admission 30 days before diagnosis. Factors associated with delayed TTI ≥45 days were assessed using multivariable logistic regression. RESULTS: Among 2,328 patients (mean [standard deviation] age, 64.0 (12.8) years; 66.6% female), having >1 unmet social need was associated with delayed TTI (odds ratio [OR], 1.68; 95% CI, 1.54 to 1.82). The disparities most associated with delay were legal help, transportation, housing stability, and needing to provide care for others. Those with ED (OR, 0.49; 95% CI, 0.44 to 0.54) or inpatient (OR, 0.54; 95% CI, 0.50 to 0.58) admission 30 days before diagnosis were less likely to experience delay. CONCLUSION: Delays in oncologic TTI ≥45 days are independently associated with unmet social needs. ED or inpatient admissions before diagnosis increase care coordination, leading to improved TTI. Although limitations included the retrospective nature of the study and self-reporting bias, these findings more precisely identify targets for intervention that may more effectively decrease delay. Patients with SDoH barriers are at higher risk of treatment delay and could especially benefit from legal, transportation, caregiver, and housing assistance.

Complications related to thyroidectomy among patients with hyperthyroidism: Exploring the potential for ambulatory surgery.

BACKGROUND: Total thyroidectomy for hyperthyroidism is typically followed by overnight admission to monitor for complications including thyrotoxicosis. Outpatient thyroid surgery is increasingly common, but its safety in patients with hyperthyroidism has not been well studied. METHODS: This retrospective study reviewed 183 patients with hyperthyroidism who underwent total thyroidectomy from 2015 to 2022 at one urban, academic center. The main outcomes were rates of thyroid storm, surgical complications, and 30-day ED visits and readmissions. RESULTS: Among 183 patients with hyperthyroidism (mean age, 45 ± 14.5 years; 82.5% female), there were no cases of thyroid storm and complications included recurrent laryngeal nerve (RLN) palsy (7.0%), symptomatic hypocalcemia (4.4%), and hematoma (1.6%). ED visits were present in 1.1% and no patients were readmitted. CONCLUSION: Total thyroidectomy was not associated with thyroid storm and <6% of patients required inpatient management. Ambulatory total thyroidectomy for hyperthyroidism warrants further consideration through identification of predictive factors for postoperative complications.

Adaptive and non-adaptive convergent evolution in feather reflectance of California Channel Islands songbirds.

Convergent evolution is widely regarded as a signature of adaptation. However, testing the adaptive consequences of convergent phenotypes is challenging, making it difficult to exclude non-adaptive explanations for convergence. Here, we combined feather reflectance spectra and phenotypic trajectory analyses with visual and thermoregulatory modelling to test the adaptive significance of dark plumage in songbirds of the California Channel Islands. By evolving dark dorsal plumage, island birds are generally less conspicuous to visual-hunting raptors in the island environment than mainland birds. Dark dorsal plumage also reduces the energetic demands associated with maintaining homeothermy in the cool island climate. We also found an unexpected pattern of convergence, wherein the most divergent island populations evolved greater reflectance of near-infrared radiation. However, our heat flux models indicate that elevated near-infrared reflectance is not adaptive. Analysis of feather microstructure suggests that mainland-island differences are related to coloration of feather barbs and barbules rather than their structure. Our results indicate that adaptive and non-adaptive mechanisms interact to drive plumage evolution in this system. This study sheds light on the mechanisms driving the association between dark colour and wet, cold environments across the tree of life, especially in island birds.

Plumage Balances Camouflage and Thermoregulation in Horned Larks (Eremophila alpestris).

AbstractAnimal coloration serves many biological functions and must therefore balance potentially competing selective pressures. For example, many animals have camouflage in which coloration matches the visual background that predators scan for prey. However, different colors reflect different amounts of solar radiation and may therefore have thermoregulatory implications as well. In this study, we examined geographic variation in dorsal patterning, coloration, and solar reflectance among horned larks (Eremophila alpestris) of the western United States. We found that plumage brightness was positively associated with soil granularity, aridity, and temperature. Plumage redness-both in terms of saturation (i.e., chroma) and hue-was positively associated with soil redness and temperature, while plumage patterning was positively associated with soil granularity. Together, these plumage-environment associations support both background matching and Gloger's rule, a widespread ecogeographic pattern in animal coloration. We also constructed thermoregulatory models that estimated cooling benefits provided by solar reflectance profiles of the dorsal plumage of each specimen based on the collection site. We found increased cooling benefits in hotter, more arid environments. Finally, cooling benefits were positively associated with residual brightness, such that individuals that were brighter than expected based on environmental conditions also had higher cooling benefits, suggesting a trade-off between camouflage and thermoregulation. Together, these data suggest that natural selection has balanced camouflage and thermoregulation in horned larks, and they illustrate how multiple competing evolutionary pressures may interact to shape geographic variation in adaptive phenotypes.

Evaluation of a comprehensive maternal newborn health intervention in rural Tanzania: single-arm pre-post coverage survey results.

BACKGROUND: In Tanzania, maternal and newborn deaths can be prevented via quality facility-based antenatal care (ANC), delivery, and postnatal care (PNC). Scalable, integrated, and comprehensive interventions addressing demand and service-side care-seeking barriers are needed. OBJECTIVE: Assess coverage survey indicators before and after a comprehensive maternal newborn health (MNH) intervention in Misungwi District, Tanzania. METHODS: A prospective, single-arm, pre- (2016) and post-(2019) coverage survey (ClinicalTrials.gov #NCT02506413) was used to assess key maternal and newborn health (MNH) outcomes. The Mama na Mtoto intervention included district activities (planning, leadership training, supportive supervision), health facility activities (training, equipment, infrastructure upgrades), and plus community health worker mobilization. Implementation change strategies, a process model, and a motivational framework incorporated best practices from a similar Ugandan intervention. Cluster sampling randomized hamlets then used 'wedge sampling' protocol as an alternative to full household enumeration. Key outcomes included: four or more ANC visits (ANC4+); skilled birth attendant (SBA); PNC for mother within 48 hours (PNC-woman); health facility delivery (HFD); and PNC for newborn within 48 hours (PNC-baby). Trained interviewers administered the 'Real Accountability: Data Analysis for Results Coverage Survey to women 15-49 years old. Descriptive statistics incorporated design effect; the Lives Saved Tool estimated deaths averted based on ANC4+/HFD. RESULTS: Between baseline (n = 2,431) and endline (n = 2,070), surveys revealed significant absolute percentage increases for ANC4+ (+11.6, 95% CI [5.4, 17.7], p < 0.001), SBA (+16.6, 95% CI [11.1, 22.0], p < 0.001), PNC-woman (+9.2, 95% CI [3.2, 15.2], p = 0.002), and HFD (+17.2%, 95% CI [11.3, 23.1], p < 0.001). A PNC-baby increase (+6.1%, 95% CI [-0.5, 12.8], p = 0.07) was not statistically significant. An estimated 121 neonatal and 20 maternal lives were saved between 2016 and 2019. CONCLUSIONS: Full-district scale-up of a comprehensive MNH package embedded government health system was successfully implemented over a short time and associated with significant maternal care-seeking improvements and potential for lives saved.

The fear of social stigma experienced by men: a barrier to male involvement in antenatal care in Misungwi District, rural Tanzania.

BACKGROUND: Evidence has shown that male involvement is associated with improved maternal health outcomes. In rural Tanzania, men are the main decision makers and may determine women's access to health services and ultimately their health outcomes. Despite efforts geared towards enhancing male participation in maternal health care, their involvement in antenatal care (ANC) remains low. One barrier that impacts men's participation is the fear and experience of social stigma. This study, builds on previous findings about men's perspectives in attending antenatal care appointments in Misungwi district in Tanzania, examining more closely the fear of social stigma amongst men attending ANC together with their partners. METHODS: Twelve individual interviews and five focus group discussions were conducted using semi-structured questionnaires with fathers and expectant fathers. In-depth interviews were conducted with health providers, volunteer community health workers and village leaders. Interviews were audiotaped, and transcripts were transcribed and translated to English. Transcripts were organized in NVivo V.12 then analyzed using thematic approach. RESULTS: Three main themes were found to create fear of social stigma for men: 1. Fear of HIV testing; 2. Traditional Gender Norms and 3. Insecurity about family social and economic status. CONCLUSION: Respondent's experiences reveal that fear of social stigma is a major barrier to attend ANC services with their partners. Attention must be given to the complex sociocultural norms and social context that underly this issue at the community level. Strategies to address fear of social stigma require an understanding of the real reasons some men do not attend ANC and require community engagement of community health workers (CHWs), government officials and other stakeholders who understand the local context.

Mapping Artisanal and Small-Scale Gold Mining in Senegal Using Sentinel 2 Data.

Artisanal and small-scale gold mining (ASGM) represents a significant economic activity for communities in developing countries. In southeastern Senegal, this activity has increased in recent years and has become the main source of income for the local population. However, it is also associated with negative environmental, social, and health impacts. Considering the recent development of ASGM in Senegal and the difficulties of the government in monitoring and regulating this activity, this article proposes a method for detecting and mapping ASGM sites in Senegal using Sentinel 2 data and the Google Earth Engine. Two artisanal mining sites in Senegal are selected to test this approach. Detection and mapping are achieved following a processing pipeline. Principal component analysis (PCA) is applied to determine the optimal period of the year for mapping. Separability and threshold (SEaTH) is used to determine the optimal bands or spectral indices to discriminate ASGM from other land use. Finally, automatic classification and mapping of the scenes are achieved with support vector machine (SVM) classifier. The results are then validated based on field observations. The PCA and examination of spectral signatures as a function of time indicate that the best period for discriminate ASGM sites against other types of land use is the end of dry season, when vegetation is minimal. The classification results are presented as a map with different categories of land use. This method could be applied to future Sentinel scenes to monitor the evolution of mining sites and may also be extrapolated to other relevant areas in the Sahel.

Female respondent acceptance of computer-assisted personal interviewing (CAPI) for maternal, newborn and child health coverage surveys in rural Uganda.

INTRODUCTION: High maternal and child mortality continues in low- and middle-income countries (LMIC). Measurement of maternal, newborn and child health (MNCH) coverage indicators often involves an expensive, complex, and lengthy household data collection process that is especially difficult in less-resourced settings. Computer-assisted personal interviewing (CAPI) has been proposed as a cost-effective and efficient alternative to traditional paper-and-pencil interviewing (PAPI). However, the literature on respondent-level acceptance of CAPI in LMIC has reported mixed outcomes. This is the first study to prospectively examine female respondent acceptance of CAPI and its influencing factors for MNCH data collection in rural Southwest Uganda. METHODS: Eighteen women aged 15-49 years were randomly selected from 3 rural villages to participate. Each respondent was administered a Women's Questionnaire with half of the survey questions asked using PAPI techniques and the other half using CAPI. Following this PAPI/CAPI exposure, semi-structured focus group discussions (FGDs) assessed respondent attitudes towards PAPI versus CAPI. FGD data analysis involved an immersion/crystallization method (thematic narrative analysis). RESULTS: The sixteen FGD respondents had a median age of 27 (interquartile range: 24.8, 32.3) years old. The majority (62.5%) had only primary level education. Most respondents (68.8%) owned or regularly used a mobile phone or computer. Few respondents (31.3%) had previously seen but not used a tablet computer. Overall, FGDs revealed CAPI acceptance and the factors influencing CAPI acceptability were 'familiarity', 'data confidentiality and security', 'data accuracy', and 'modernization and development'. DISCUSSION: Female survey respondents in our rural Southwest Ugandan setting found CAPI to be acceptable. Global health planners and implementers considering CAPI for health coverage survey data collection should accommodate influencing factors during survey planning in order to maximize and facilitate acceptance and support by local stakeholders and community participants. Further research is needed to generate best practices for CAPI implementation and LMIC; higher quality, timely, streamlined and budget-friendly collection of MNCH indicators could help direct and improve programming to save lives of mothers and children.

Drugs for some but not all: inequity within community health worker teams during introduction of integrated community case management.

BACKGROUND: The Ugandan health system now supports integrated community case management (iCCM) by community health workers (CHWs) to treat young children ill with fever, presumed pneumonia, and diarrhea. During an iCCM pilot intervention study in southwest Uganda, two CHWs were selected from existing village teams of two to seven CHWs, to be trained in iCCM. Therefore, some villages had both 'basic CHWs' who were trained in standard health promotion and 'iCCM CHWs' who were trained in the iCCM intervention. A qualitative study was conducted to investigate how providing training, materials, and support for iCCM to some CHWs and not others in a CHW team impacts team functioning and CHW motivation. METHODS: In 2012, iCCM was implemented in Kyabugimbi sub-county of Bushenyi District in Uganda. Following seven months of iCCM intervention, focus group discussions and key informant interviews were conducted alongside other end line tools as part of a post-iCCM intervention study. Study participants were community leaders, caregivers of young children, and the CHWs themselves ('basic' and 'iCCM'). Qualitative content analysis was used to identify prominent themes from the transcribed data. RESULTS: The five main themes observed were: motivation and self-esteem; selection, training, and tools; community perceptions and rumours; social status and equity; and cooperation and team dynamics. 'Basic CHWs' reported feeling hurt and overshadowed by 'iCCM CHWs' and reported reduced self-esteem and motivation. iCCM training and tools were perceived to be a significant advantage, which fueled feelings of segregation. CHW cooperation and team dynamics varied from area to area, although there was an overall discord amongst CHWs regarding inequity in iCCM participation. Despite this discord, reasonable personal and working relationships within teams were retained. CONCLUSIONS: Training and supporting only some CHWs within village teams unexpectedly and negatively impacted CHW motivation for 'basic CHWs', but not necessarily team functioning. A potential consequence might be reduced CHW productivity and increased attrition. CHW programmers should consider minimizing segregation when introducing new program opportunities through providing equal opportunities to participate and receive incentives, while seeking means to improve communication, CHW solidarity, and motivation.

Breastfeeding difficulties and exclusivity among late preterm and term infants: results from the all our babies study.

OBJECTIVE: To compare breastfeeding difficulties attributable to the baby and mother/milk and exclusive breastfeeding between a group of late preterm (LP) infants and term infants. METHODS: We utilized data from a prospective community-based cohort (n=2977) in Calgary, Alberta, and performed bivariate and multivariable analyses to identify demographic, obstetric, maternal and infant health indicators that were independently associated with term status and breastfeeding outcomes. RESULTS: Multivariable analyses found that LP status was an independent risk factor for breastfeeding difficulties attributable to the baby (OR 1.72, 95% CI 1.24-2.38), but not for difficulties due to mother/milk (defined as not producing enough milk or having flat or inverted nipples). Among women who were breastfeeding at hospital discharge, mothers of LP infants were less likely to report exclusive breastfeeding at 4 months (OR 0.67, 95% CI 0.46-0.97), after controlling for household income level, mode of delivery and postpartum maternal physical health. CONCLUSIONS: Mothers of LP infants need increased support to establish successful breastfeeding outcomes and to ensure that these infants receive the full benefits of breast milk.

Health-economic analysis: cost-effectiveness of scheduled maintenance treatment with infliximab for Crohn's disease--modelling outcomes in active luminal and fistulizing disease in adults.

BACKGROUND: Infliximab has been shown to be efficacious in moderate-to-severe Crohn's disease (CD). AIM: To evaluate the cost-effectiveness of scheduled maintenance treatment with infliximab in luminal and fistulizing CD patients. METHODS: Markov models were constructed to simulate the progression of adult CD patients with and without fistulae during treatment with infliximab (5 mg/kg). Transitions were estimated from published clinical trials of infliximab. Standard care, comprising immunomodulators and/or corticosteroids was used as a comparator. An average weight of 60 kg was used to estimate the dose of infliximab. The costs and outcomes were discounted at 3.5% over 5 years. The primary effectiveness measurement was quality-adjusted life years (QALYs) estimated using EQ-5D. One-way and probabilistic sensitivity analyses were performed by varying the infliximab efficacy estimates, costs and utilities. RESULTS: The incremental cost per QALY gained was pound 26,128 in luminal CD and pound 29,752 in fistulizing CD at 5 years. Results were robust and remained in the range of pound 23,752- pound 38,848 for luminal CD and pound 27,047- pound 44,206 for fistulizing CD. Patient body weight was the most important factor affecting cost-effectiveness. CONCLUSION: Eight-week scheduled maintenance treatment with infliximab is a cost-effective treatment for adult patients suffering from active luminal or fistulizing CD.

Military nursing research by students at the Graduate School of Nursing Uniformed Services University of the Health Sciences.

Military nursing research has had a long and productive history. Today, much of this research is conducted under two programs, the TriService Nursing Research Program and the Graduate School of Nursing (GSN), both located at the Uniformed Services University of the Health Sciences in Bethesda, Maryland. This article will discuss the 150 military nursing research projects carried out by students at the GSN since its founding in 1992. Although most projects have been small in scope, they have obtained useful results. Some projects have served as the basis for larger-scale research studies, receiving funding from the TriService Nursing Research Program. Reports of all projects are available in an online database and some have been published in professional journals. This review concludes that the research produced by GSN students has been beneficial to students and to the military health system.

Physical interaction of Cdc28 with Cdc37 in Saccharomyces cerevisiae.

The Cdc37 protein in Saccharomyces cerevisiae is thought to be a kinase-targeting subunit of the chaperone Hsp90. In a genetic screen, four protein kinases were identified as interacting with Cdc37 - Cdc5, Cdc7, Cdc15 and Cak1. This result underlines the importance of Cdc37 for the folding of protein kinases. In addition, we showed that Ydj1, a yeast DnaJ homolog belonging to the Hsp40 family of chaperones, genetically interacts with Cdc37. No physical interaction has so far been detected between Cdc37 and Cdc28, although genetic interactions (synthetic lethality and mutation suppression), and biochemical studies have suggested that these two proteins functionally interact. We found that, when separately expressed, the N-terminal lobe of Cdc28 interacted strongly with the C-terminal moiety of Cdc37 in a two-hybrid system. This was not the case for the full-length Cdc28 protein. We present models to explain these results.

In vivo gene therapy for colon cancer using adenovirus-mediated, transfer of the fusion gene cytosine deaminase and uracil phosphoribosyltransferase.

Virus-directed enzyme prodrug therapy (VDEPT) utilising cytosine deaminase (CD) converts 5-fluorocytosine (5-FC) into the chemotherapy agent, 5-fluorouracil (5-FU), and has entered into a clinical trial for metastatic colon cancer. To improve this system, a replication-deficient adenovirus, containing a bifunctional fusion gene, CD:uracil phosphoribosyltransferase (UPRT), was constructed (AdCDUPRT). UPRT enhances the conversion of 5-FU into its active metabolites, which inhibit DNA and RNA synthesis. In vitro, AdCDUPRT infection of colon cancer cells resulted in a marked increase in sensitisation to 5-FU, compared with AdCD-infected or uninfected cells. The corollary is a approximately 100-fold and approximately 10 000-fold increase in sensitisation to 5-FC in AdCDUPRT-infected cells, compared to AdCD-infected and uninfected cells, respectively. There was a strong bystander effect in vitro, 70% of tumour cells were killed by 5-FC when only 10% of cells expressed CDUPRT. In vivo, athymic mice with colon cancer xenografts treated with intratumoral AdCDUPRT and intraperitoneal 5-FC, significantly reduced tumour growth rates compared with untreated controls (P = 0.02), whereas AdCD/5-FC treated mice did not. At higher AdCDUPRT virus doses, 5-FC and 5-FU were equally effective at delaying tumour growth compared with controls. In summary, VDEPT for colon cancer utilising AdCDUPRT is more effective than AdCD and the bifunctional CDUPRT gene enables the use of either 5-FC or 5-FU as prodrugs.

Virus-directed, enzyme prodrug therapy with nitroimidazole reductase: a phase I and pharmacokinetic study of its prodrug, CB1954.

CB1954 [5-(aziridin-1-yl)-2,4-dinitrobenzamide] is converted by the bacterial enzyme nitroimidazole reductase (NTR) into a potent cytotoxic bifunctional alkylating agent, which can be delivered to tumors in adenoviral vectors as virus-directed, enzyme prodrug therapy. This report summarizes a Phase I and pharmacokinetic study of the prodrug, CB1954. Thirty patients, ages 23-78 years (median 62 years), with predominantly gastrointestinal malignancies were treated. CB1954 was administered by i.v. injection every 3 weeks or i.p. followed by 3-weekly i.v. injections, toward a maximum of six cycles. The dose was escalated from 3 to 37.5 mg/m2. No significant toxicity was seen until 24 mg/m2 (recommended i.v. dose). Dose-limiting toxicities (DLT) were diarrhea and hepatic toxicity, seen at 37.5 mg/m2. DLT has not been observed at the current i.p. dose of 24 mg/m2. There was no alopecia, marrow suppression, or nephrotoxicity. Clearance data suggest hepatic metabolism, and <5% of CB1954 was renally excreted. There was a nonlinear relationship between i.v. dose and area under the curve (AUC). At the recommended i.v. dose of 24 mg/m2, the AUC was 5.8 microM/h. Intraperitoneal administration (24 mg/m2) achieved an AUC of 387 microM/h, giving a considerable regional advantage. In vitro, the AUC required to achieve the IC50 for CB1954, in NTR-expressing cancer cells, ranges from 10-50 microM/h. Thus, CB1954 is well tolerated at a dose of 24 mg/m2, and sufficient serum/peritoneal levels are achieved for an enzyme-prodrug approach to be feasible. We are now conducting a Phase I trial combining adenovirus-mediated NTR and i.v. CB1954 (24 mg/m2) in patients with primary and secondary liver tumors.

Gene therapy for colorectal cancer: therapeutic potential.

Colorectal cancer is a leading cause of cancer mortality in Western countries. Gene therapy has been proposed as a potential novel treatment modality for colorectal cancer, but it is still in an early stage of development. The preclinical data have been promising and numerous clinical trials are underway. This brief review aims to summarise the current status of clinical trials of different gene therapy strategies, including immune stimulation, mutant gene correction, prodrug activation and oncolytic virus therapy, for patients with colorectal cancer. Data from phase I trials have proven the safety of the reagents but have not yet demonstrated significant therapeutic benefit. In order to achieve this and extend the scope of the treatment, continuing efforts should be made to improve the antitumour potency, efficiency of gene delivery and accuracy of gene targeting.

Xbp1-mediated repression of CLB gene expression contributes to the modifications of yeast cell morphology and cell cycle seen during nitrogen-limited growth.

Yeast cells undergo morphological transformations in response to diverse environmental signals. One such event, called pseudohyphal differentiation, occurs when diploid yeast cells are partially starved for nitrogen on a solid agar medium. The nitrogen-starved cells elongate, and a small fraction form filaments that penetrate the agar surface. The molecular basis for the changes in cell morphology and cell cycle in response to nitrogen limitation are poorly defined, in part because the heterogeneous growth states of partially starved cells on agar media are not amenable to biochemical analysis. In this work, we used chemostat cultures to study the role of cell cycle regulators with respect to yeast differentiation in response to nitrogen limitation under controlled, homogeneous culture conditions. We found that Clb1, Clb2, and Clb5 cyclin levels are reduced in nitrogen-limited chemostat cultures compared to levels in rich-medium cultures, whereas the Xbp1 transcriptional repressor is highly induced under these conditions. Furthermore, the deletion of XBP1 prevents the drop in Clb2 levels and inhibits cellular elongation in nitrogen-limited chemostat cultures as well as inhibiting pseudohyphal growth on nitrogen-limited agar media. Deletion of the CLB2 gene restores an elongated morphology and filamentation to the xbp1Delta mutant in response to nitrogen limitation. Transcriptional activation of the XBP1 gene and the subsequent repression of CLB gene expression are thus key responses of yeast cells to nitrogen limitation.