The other side of the coin: An integrative review connecting pay and health.

The organizational sciences have long been interested in the effects of various compensation strategies, and on enhancing employee health. Research examining the connection between pay and health, however, remains a relative rarity. The work that has been done is scattered across disparate disciplines and lacks a unified framework for systematically exploring the effects of pay on health. We argue that greater insecurity at work, as well as rising discontent over wages and work conditions, necessitates a richer understanding of the ways in which organizational pay affects employee psychological, physiological, and behavioral health. We first conduct a comprehensive review of existing research across a broad range of disciplines, taking note of the different ways that pay is conceptualized and the impact it has on employee health. We identify critical knowledge gaps in why and when pay is related to health, noting several disciplinary trends. Drawing on prominent theories of occupational health, we then build a theoretical framework that illustrates three mechanisms underlying the effect of pay on health. We further advance prior work by integrating allostatic load theory to explain how pay gets "under the skin" to affect health, while also identifying relevant moderators and boundary conditions. Taken together, our review integrates findings from a variety of disciplines and facilitates knowledge building across these fields to generate a more comprehensive understanding of the connection between pay and health. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Ex-vivo drug screening of surgically resected glioma stem cells to replace murine avatars and provide personalise cancer therapy for glioblastoma patients.

With diminishing returns and high clinical failure rates from traditional preclinical and animal-based drug discovery strategies, more emphasis is being placed on alternative drug discovery platforms. Ex vivo approaches represent a departure from both more traditional preclinical animal-based models and clinical-based strategies and aim to address intra-tumoural and inter-patient variability at an earlier stage of drug discovery. Additionally, these approaches could also offer precise treatment stratification for patients within a week of tumour resection in order to direct tailored therapy. One tumour group that could significantly benefit from such ex vivo approaches are high-grade gliomas, which exhibit extensive heterogeneity, cellular plasticity and therapy-resistant glioma stem cell (GSC) niches. Historic use of murine-based preclinical models for these tumours has largely failed to generate new therapies, resulting in relatively stagnant and unacceptable survival rates of around 12-15 months post-diagnosis over the last 50 years. The near universal use of DNA damaging chemoradiotherapy after surgical resection within standard-of-care (SoC) therapy regimens provides an opportunity to improve current treatments if we can identify efficient drug combinations in preclinical models that better reflect the complex inter-/intra-tumour heterogeneity, GSC plasticity and inherent DNA damage resistance mechanisms. We have therefore developed and optimised a high-throughput ex vivo drug screening platform; GliExP, which maintains GSC populations using immediately dissociated fresh surgical tissue. As a proof-of-concept for GliExP, we have optimised SoC therapy responses and screened 30+ small molecule therapeutics and preclinical compounds against tumours from 18 different patients, including multi-region spatial heterogeneity sampling from several individual tumours. Our data therefore provides a strong basis to build upon GliExP to incorporate combination-based oncology therapeutics in tandem with SoC therapies as an important preclinical alternative to murine models (reduction and replacement) to triage experimental therapeutics for clinical translation and deliver rapid identification of effective treatment strategies for individual gliomas.

Diagnosis, treatment, and survival from kidney cancer: real-world National Health Service England data between 2013 and 2019.

OBJECTIVES: To report the NHS Digital (NHSD) data for patients diagnosed with kidney cancer (KC) in England. We explore the incidence, route to diagnosis (RTD), treatment, and survival patterns from 2013 to 2019. MATERIALS AND METHODS: Data was extracted from the Cancer Data NHSD portal for International Classification of Diseases, 10th edition coded KC; this included Cancer Registry data, Hospital Episode Statistics, and cancer waiting times data. RESULTS: Registrations included 66 696 individuals with KC. Incidence of new KC diagnoses increased (8998 in 2013, to 10 232 in 2019), but the age-standardised rates were stable (18.7-19.4/100 000 population). Almost half of patients (30 340 [45.5%]) were aged 0-70 years and the cohort were most frequently diagnosed with Stage 1-2 KC (n = 26 297 [39.4%]). Most patients were diagnosed through non-urgent general practitioner referrals (n = 16 814 [30.4%]), followed by 2-week-wait (n = 15 472 [28.0%]) and emergency routes (n = 11 796 [21.3%]), with older patients (aged ≥70 years), Stage 4 KCs, and patients with non-specified renal cell carcinoma being significantly more likely to present through the emergency route (all P < 0.001). Invasive treatment (surgery or ablation), radiotherapy, or systemic anti-cancer therapy use varied with disease stage, patient factors, and treatment network (Cancer Alliance). Survival outcomes differed by Stage, histological subtype, and social deprivation class (P < 0.001). Age-standardised mortality rates did not change over the study duration, although immunotherapy usage is likely not captured in this study timeline. CONCLUSION: The NHSD resource provides useful insight about the incidence, diagnostic pathways, treatment, and survival of patients with KC in England and a useful benchmark for the upcoming commissioned National Kidney Cancer Audit. The RTD data may be limited by incidental diagnoses, which could confound the high proportion of 'emergency' diagnoses. Importantly, survival outcomes remained relatively unchanged.

Acute haemorrhage from a large renal epithelioid angiomyolipoma: diagnostic and management considerations in a teenage patient with a rare cancer.

Acute renal haemorrhage is a life-threatening condition that is complicated in the context of renal malignancy. Here, we present the case of a teenage male presenting acutely with a large, bleeding renal epithelioid angiomyolipoma (EAML) of the kidney-a rare cancer, which is part of the perivascular epithelioid cell tumour family. The patient was managed acutely with prompt resuscitation, transfer to a centre of expertise and haemorrhagic control using radiologically guided endovascular techniques; this subsequently permitted an oncologically sound procedure (radical nephrectomy, inferior vena cava thrombectomy and lymphadenectomy) to be performed within 24 hours. The description and discussion around this unique case summarises the patient's clinical journey, while exploring the current literature surrounding diagnosis and outcomes of patients with renal EAMLs.

Hyperthermic intravesical chemotherapy with mitomycin-C for the treatment of high-risk non-muscle-invasive bladder cancer patients.

Objectives: The objectives of the study are to explore tolerability, acceptability and oncological outcomes for patients with high-risk non-muscle-invasive bladder cancer (NMIBC) treated with hyperthermic intravesical chemotherapy (HIVEC) and mitomycin-C (MMC) at our institution. Patients and Methods: Our single-institution, observational study consists of consecutive high-risk NMIBC patients treated with HIVEC and MMC. Our HIVEC protocol included six weekly instillations (induction), followed by two further cycles of three instillations (maintenance) (6 + 3 + 3) if there was cystoscopic response. Patient demographics, instillation dates and adverse events (AEs) were collected prospectively in our dedicated HIVEC clinic. Retrospective case-note review was performed to evaluate oncological outcomes. Primary outcomes were tolerability and acceptability of HIVEC protocol; secondary outcomes were 12-month recurrence-free, progression-free and overall survival. Results: In total, 57 patients (median age 80.3 years) received HIVEC and MMC, with a median follow-up of 18 months. Of these, 40 (70.2%) had recurrent tumours, and 29 (50.9%) had received prior Bacillus Calmette-Guérin (BCG). HIVEC induction was completed by 47 (82.5%) patients, but only 19 (33.3%) completed the full protocol. Disease recurrence (28.9%) and AEs (28.9%) were the most common reasons for incompletion of protocol; five (13.2%) patients stopped treatment due to logistical challenges. AEs occurred in 20 (35.1%) patients; the most frequently documented were rash (10.5%), urinary tract infection (8.8%) and bladder spasm (8.8%). Progression during treatment occurred in 11 (19.3%) patients, 4 (7.0%) of whom had muscle invasion and 5 (8.8%) subsequently required radical treatment. Patients who had received prior BCG were significantly more likely to progress (p = 0.04). 12-month recurrence-free, progression-free and overall survival rates were 67.5%, 82.2%, and 94.7%, respectively. Conclusions: Our single-institution experience suggests that HIVEC and MMC are tolerable and acceptable. Oncological outcomes in this predominantly elderly, pretreated cohort are promising; however, disease progression was higher in patients pretreated with BCG. Further randomised noninferiority trials comparing HIVEC versus BCG in high-risk NMIBC are required.

Precision oncology using ex vivo technology: a step towards individualised cancer care?

Despite advances in cancer genomics and the increased use of genomic medicine, metastatic cancer is still mostly an incurable and fatal disease. With diminishing returns from traditional drug discovery strategies, and high clinical failure rates, more emphasis is being placed on alternative drug discovery platforms, such as ex vivo approaches. Ex vivo approaches aim to embed biological relevance and inter-patient variability at an earlier stage of drug discovery, and to offer more precise treatment stratification for patients. However, these techniques also have a high potential to offer personalised therapies to patients, complementing and enhancing genomic medicine. Although an array of approaches are available to researchers, only a minority of techniques have made it through to direct patient treatment within robust clinical trials. Within this review, we discuss the current challenges to ex vivo approaches within clinical practice and summarise the contemporary literature which has directed patient treatment. Finally, we map out how ex vivo approaches could transition from a small-scale, predominantly research based technology to a robust and validated predictive tool. In future, these pre-clinical approaches may be integrated into clinical cancer pathways to assist in the personalisation of therapy choices and to hopefully improve patient experiences and outcomes.

Genome-wide Meta-analysis Identifies Novel Genes Associated with Recurrence and Progression in Non-muscle-invasive Bladder Cancer.

BACKGROUND: Non-muscle-invasive bladder cancer (NMIBC) is characterized by frequent recurrences and a risk of progression in stage and grade. Increased knowledge of underlying biological mechanisms is needed. OBJECTIVE: To identify single nucleotide polymorphisms (SNPs) associated with recurrence-free (RFS) and progression-free (PFS) survival in NMIBC. DESIGN, SETTING, AND PARTICIPANTS: We analyzed outcome data from 3400 newly diagnosed NMIBC patients from the Netherlands, the UK, Canada, and Spain. We generated genome-wide germline SNP data using Illumina OmniExpress and Infinium Global Screening Array in combination with genotype imputation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cohort-specific genome-wide association studies (GWASs) for RFS and PFS were performed using a Cox proportional hazard model. Results were combined in a fixed-effect inverse-variance weighted meta-analysis. Candidate genes for the identified SNP associations were prioritized using functional annotation, gene-based analysis, expression quantitative trait locus analysis, and transcription factor binding site databases. Tumor expression levels of prioritized genes were tested for association with RFS and PFS in an independent NMIBC cohort. RESULTS AND LIMITATIONS: This meta-analysis revealed a genome-wide significant locus for RFS on chromosome 14 (lead SNP rs12885353, hazard ratio [HR] C vs T allele 1.55, 95% confidence interval [CI] 1.33-1.82, p = 4.0 × 10-8), containing genes G2E3 and SCFD1. Higher expression of SCFD1 was associated with increased RFS (HR 0.70, 95% CI 0.59-0.84, pFDR = 0.003). Twelve other loci were suggestively associated with RFS (p < 10-5), pointing toward 18 additional candidate genes. For PFS, ten loci showed suggestive evidence of association, indicating 36 candidate genes. Expression levels of ten of these genes were statistically significantly associated with PFS, of which four (IFT140, UBE2I, FAHD1, and NME3) showed directional consistency with our meta-analysis results and published literature. CONCLUSIONS: In this first prognostic GWAS in NMIBC, we identified several novel candidate loci and five genes that showed convincing associations with recurrence or progression. PATIENT SUMMARY: In this study, we searched for inherited DNA changes that affect the outcome of non-muscle-invasive bladder cancer (NMIBC). We identified several genes that are associated with disease recurrence and progression. The roles and mechanisms of these genes in NMIBC prognosis should be investigated in future studies.

Radical Cystectomy Against Intravesical BCG for High-Risk High-Grade Nonmuscle Invasive Bladder Cancer: Results From the Randomized Controlled BRAVO-Feasibility Study.

PURPOSE: High-grade nonmuscle invasive bladder cancer (HRNMIBC) is a heterogeneous disease. Treatments include intravesical maintenance Bacillus Calmette-Guerin (mBCG) and radical cystectomy (RC). We wanted to understand whether a randomized trial comparing these options was possible. MATERIALS AND METHODS: We conducted a two-arm, prospective multicenter randomized study to determine the feasibility in Bacillus Calmette-Guerin-naive patients. Participants had new high-risk HRNMIBC suitable for both treatments. Random assignment was stratified by age, sex, center, stage, presence of carcinoma in situ, and prior low-risk bladder cancer. Qualitative work investigated how to maintain equipoise. The primary outcome was the number of patients screened, eligible, recruited, and randomly assigned. RESULTS: We screened 407 patients, approached 185, and obtained consent from 51 (27.6%) patients. Of these, one did not proceed and therefore 50 were randomly assigned (1:1). In the mBCG arm, 23/25 (92.0%) patients received mBCG, four had nonmuscle invasive bladder cancer (NMIBC) after induction, three had NMIBC at 4 months, and four received RC. At closure, two patients had metastatic BC. In the RC arm, 20 (80.0%) participants received cystectomy, including five (25.0%) with no tumor, 13 (65.0%) with HRNMIBC, and two (10.0%) with muscle invasion in their specimen. At follow-up, all patients in the RC arm were free of disease. Adverse events were mostly mild and equally distributed (15/23 [65.2%] patients with mBCG and 13/20 [65.0%] patients with RC). The quality of life (QOL) of both arms was broadly similar at 12 months. CONCLUSION: A randomized controlled trial comparing mBCG and RC will be challenging to recruit into. Around 10% of patients with high-risk HRNMIBC have a lethal disease and may be better treated by primary radical treatment. Conversely, many are suitable for bladder preservation and may maintain their prediagnosis QOL.

Comparing open-radical cystectomy and robot-assisted radical cystectomy: current status and analysis of the evidence.

PURPOSE OF REVIEW: Radical cystectomy is the definitive surgical treatment for aggressive bladder cancer. The robotic platform offers a new approach to radical cystectomy, but the benefits are unclear. This review examines the latest evidence, with a particular focus on developments in the last two years. RECENT FINDINGS: Prospective evaluations of open (ORC) and robot-assisted radical cystectomy (RARC) are emerging. The radical cystectomy in patients with bladder cancer trial reported in 2018 and demonstrated oncological noninferiority for both approaches and marginal shorter length of stays with RARC using an extracorporeal reconstruction. The trial confirmed prospective randomized comparisons are possible, and replicates observations from two earlier, smaller randomised controlled trials with longer follow-up. Although there has been significant traction to the intracorporeal approach to RARC, randomized trial evidence is awaited to show any benefit over ORC. SUMMARY: New evidence alludes to the noninferiority of the robotic platform in radical cystectomy in comparison to open surgery. There is minimal evidence of a clinically meaningful benefit. Until this is addressed, ORC remains the gold standard for the definitive surgical management of bladder cancer.

Non-visible haematuria for the Detection of Bladder, Upper Tract, and Kidney Cancer: An Updated Systematic Review and Meta-analysis.

CONTEXT: Non-visible haematuria (NVH) is a common finding and may indicate undiagnosed urological cancer. The optimal investigation of NVH is unclear, given the incidence of cancer and the public health implications of testing all individuals with this finding. OBJECTIVE: We review contemporary literature to determine the association of NVH with the diagnosis of bladder cancer (BC), upper tract urothelial carcinoma (UTUC), and kidney cancer (KC). EVIDENCE ACQUISITION: A systematic review of original articles in English was completed in May 2019. Meta-analyses for the diagnostic accuracy of NVH and urine cytology were performed. EVIDENCE SYNTHESIS: We screened 1529 articles and selected 78 manuscripts that fulfilled our inclusion criteria for narrative synthesis. Forty manuscripts were eligible for a meta-analysis (reporting 19 193 persons). The likelihood of a urological cancer in patients with NVH increased with age (<1% in those aged <40yr), male sex, and cigarette smoking. Less than 1% of patients are found to have a urological cancer after a negative NVH evaluation. Cancer detection rates in individuals evaluated for NVH ranged from 0% to 16% for BC in 37 studies, 0% to 3.5% for UTUC in 30 studies, and 0% to 9.7% for KC in 29 studies. Substantial statistical heterogeneity was present for the meta-analysis of detection rates. CONCLUSIONS: We present an up-to-date review of the association of NVH with the diagnosis of BC, UTUC, and KC. Individuals with dipstick positive haematuria aged ≥40yr, who have had potential precipitating causes excluded, should undergo an evaluation. Re-evaluation of patients with unremarkable initial investigations should be performed in high-risk patients or if new symptoms occur. PATIENT SUMMARY: One in five people have microscopic traces of blood in their urine. This is an important indicator of urological cancer. Investigating all patients is uncomfortable and expensive. We evaluate the risk of cancer and estimate risks to groups of individuals.

Unrestricted faecal calprotectin testing performs poorly in the diagnosis of inflammatory bowel disease in patients in primary care.

BACKGROUND: Faecal calprotectin (FC) measurement distinguishes patients with inflammatory bowel disease (IBD) from those with irritable bowel syndrome but evidence of its performance in primary care is limited. AIMS: To assess the yield of IBD from FC testing in primary care. METHODS: Retrospective review of hospital records to assess the outcome following FC testing in primary care. Investigations for all patients undergoing FC testing in a single laboratory for 6 months from 1 October 2013 to 28 February 2014 were reviewed. RESULTS: 410 patients (162 male; median age 42; range 16-91) were included. FC>50 µg/g was considered positive (FC+). 148/410 (36.1%; median age 44 (17-91)) were FC+ (median FC 116.5 µg/g (51-1770)). 122/148 FC-positive patients (82.4%) underwent further investigation. 97 (65.5%) underwent lower gastrointestinal endoscopy (LGIE), of which 7 (7.2%) had IBD. 49/262 (18.7%) FC-negative (FC-) patients (FC ≤50 µg/g) (median age 47 (19-76)) also underwent LGIE, of whom 3 (6.1%) had IBD.IBD was diagnosed in 11/410 (2.7%; 4 ulcerative colitis, 3 Crohn's disease, 4 microscopic colitis). 8/11 were FC+ (range 67-1170) and 3 FC-. At a 50 µg/g threshold, sensitivity for detecting IBD was 72.7%, specificity 64.9%, positive predictive value (PPV) 5.41% and negative predictive value 98.9%. Increasing the threshold to 100 µg/g reduced the sensitivity of the test for detecting IBD to 54.6%. CONCLUSIONS: FC testing in primary care has low sensitivity and specificity with poor PPV for diagnosing IBD. Its use needs to be directed to those with a higher pretest probability of disease. Local services and laboratories should advise general practitioners accordingly.

The effects of the question "What is this?" on tact-training outcomes of children with autism.

Tact training is a common element of many habilitative programs for individuals with developmental disabilities. A commonly recommended practice is to include a supplemental question (e.g., "What is this?") during training trials for tacts of objects. However, the supplemental question is not a defining feature of the tact relation, and prior research suggests that its inclusion might sometimes impede tact acquisition. The present study compared tact training with and without the supplemental question in terms of acquisition and maintenance. Two of 4 children with autism acquired tacts more efficiently in the object-only condition; the remaining 2 children acquired tacts more efficiently in the object + question condition. During maintenance tests in the absence of the supplemental question, all participants emitted tacts at end-of-training levels across conditions with no differential effect observed between training conditions.

Changes in the distribution of HIV type 1 subtypes D and A in Rakai District, Uganda between 1994 and 2002.

HIV-1 subtype D (HIV-1D) progresses to disease faster and has lower transmissibility than subtype A (HIV-1A). We examined whether these differences could lead to a population level change in the distribution of these subtypes over time. HIV-1 viral RNA was extracted from stored serum samples from HIV-positive subjects participating in a population-based cohort study in Rakai, Uganda in 1994 and 2002. Portions of the viral proteins gag and gp41 were sequenced and subtyped. HIV-1 subtype assignments were generated for 773 subjects in 1994 and 812 subjects in 2002. The change in subtype distribution of the population as a whole as well as quartile age groups were examined for significant changes using a linear model. There was a significant decrease in the proportion of subjects infected with HIV-1D from 70.2% to 62.4% and a significant increase in subjects infected with HIV-1A from 16.7% to 23.3% over the 8-year period (p = 0.005). The most marked changes in proportion of HIV-1D and A were seen in the younger individuals (<25 and 25-30 years; p < 0.05). The percentages of subjects infected with HIV-1C and recombinant subtypes did not change significantly. Over this 8-year period, the overall viral population in this region evolved toward the less virulent HIV-1A strain, most likely as a consequence of the faster disease progression and lower transmissibility of HIV-1D.

The spectrum of Trp- mutants isolated as 5-fluoroanthranilate-resistant clones in Saccharomyces bayanus, S. mikatae and S. paradoxus.

5-Fluoroanthranilic acid (FAA)-resistant mutants were selected in homothallic diploids of three Saccharomyces species, taking care to isolate mutants of independent origin. Mutations were assigned to complementation groups by interspecific complementation with S. cerevisiae tester strains. In all three species, trp3, trp4 and trp5 mutants were recovered. trp1 mutants were also recovered if the selection was imposed on a haploid strain. Thus, FAA selection may be more generally applicable than was previously described.