Expanding the prostate cancer cell line repertoire with ACRJ-PC28, an AR-negative neuroendocrine cell line derived from an African-Caribbean patient.

Prostate cell lines from diverse backgrounds are important to addressing disparities in prostate cancer (PCa) incidence and mortality rates among Black men. ACRJ-PC28 was developed from a transrectal needle biopsy and established via inactivation of the CDKN2A locus and simultaneous expression of human telomerase. Characterization assays included growth curve analysis, immunoblots, IHC, 3D cultures, immunofluorescence imaging, confocal microscopy, flow cytometry, WGS, and RNA-Seq. ACRJ-PC28 has been passaged more than 40 times in vitro over 10 months with a doubling time of 45 hours. STR profiling confirmed the novelty and human origin of the cell line. RNA-Seq confirmed the expression of prostate specific genes alpha-methylacyl-CoA racemase (AMACR) and NKX3.1 and Neuroendocrine specific markers synaptophysin (SYP) and enolase 2 (ENO2) and IHC confirmed the presence of AMACR. Immunoblots indicated the cell line is of basal-luminal type; expresses p53 and pRB and is AR negative. WGS confirmed the absence of exonic mutations and the presence of intronic variants that appear to not affect function of AR, p53, and pRB. RNA-Seq data revealed numerous TP53 and RB1 mRNA splice variants and the lack of AR mRNA expression. This is consistent with retention of p53 function in response to DNA damage and pRB function in response to contact inhibition. Soft agar anchorage-independent analysis indicated that the cells are transformed, confirmed by principal component analysis (PCA) where ACRJ-PC28 cells cluster alongside other PCa tumor tissues, yet was distinct. The novel methodology described should advance prostate cell line development, addressing the disparity in PCa among Black men.

Minimally invasive urology - Pearls, pitfalls and experience in the Caribbean.

The Caribbean is made up of several independent nations and the availability of urology and more specifically endourology services varies widely between them. In this article we explore the history and current state of endourology in the English speaking Caribbean as well as the challenges faced within the region many of which are shared by the different territories.

Surgical access for radical retropubic prostatectomy in the phenotypically narrow and steep black male's pelvis is exacerbated by a posterior pubic symphyseal protuberance: A case report.

INTRODUCTION: Men of African descent are known to have a narrower and steeper pelvis that is associated with a higher risk of positive surgical margins after radical retropubic prostatectomy. We describe the additional challenge posed when a very prominent posterior pubic symphyseal protuberance is present in the pelvis of a Black man during this operation and how to overcome it. PRESENTATION OF CASE: A 61-year old man of African-descent with organ-confined prostate cancer underwent a radical retropubic prostatectomy. He had a very prominent posterior pubic symphyseal protuberance on a background of a phenotypically narrow and steep pelvis, precluding adequate surgical access to the prostate. Using a combination of resection of the protuberance, modification of patient position and lighting, coordinated retraction and long instruments, surgical access was achieved. DISCUSSION: The coexistence of a very prominent posterior pubic symphyseal protuberance in a Black male with a narrow and steep pelvis poses a surgical challenge in accessing the prostate, particularly the apex. This can be overcome by surgical resection of the protuberance, patient waist extension by operating table flexion, use of head lamps or intracavitary lighting, adequate retraction and use of appropriately long instruments. CONCLUSION: Surgical access to the prostate, particularly its apex, when performing radical retropubic prostatectomy in a Black man with a very prominent posterior pubic symphyseal protuberance may be achieved by a combination of manoeuvres and adjuncts described herein.

Distinct breast cancer subtypes in women with early-onset disease across races.

BACKGROUND: Racial disparities among breast cancer (BCa) patients are known but not well studied in early-onset BCa. We analyzed molecular subtypes in early-onset BCa across five major races. METHODS: A total of 2120 cases were included from non-Hispanic White (NHW), African American (AA) and Hispanic, Chinese and Indian. Based on ER, PR and HER-2 status, BCa was classified into 4 intrinsic subtypes as Luminal A, Luminal B, HER2/neu overexpression and Triple negative BCa (TNBC) subtypes. Data was stratified according to race and age as younger/early-onset group (40-years and younger) and older group (50-years and older). RESULTS: In early-onset BCa, incidence of TNBC was significantly higher (p = 0.0369) in Indian women followed by AA, Hispanic, NHW and Chinese women. Incidence of Her2 over-expression subtype also was highest in Indian women, followed by Hispanic, Chinese, AA and NHW women. In contrast, Luminal B subtype was most significantly higher in AA women (p = 0.0000) followed by NHW (p = 0.0002), Chinese (p = 0.0003), Hispanic (0.0128) and Indian (p = 0.0468) women. Luminal A subtype was most significantly reduced in Indian women (p = 0.0113) followed by Hispanic, AA, NHW and Chinese women. These results were based on statistical analysis with the mean of older group populations. CONCLUSIONS: These results show significant disparities in receptor subtypes across races. This study will contribute in developing optimal clinical trial protocols and personalized management strategies for early-onset BCa patients.

Early economic evaluation of emerging health technologies: protocol of a systematic review.

BACKGROUND: The concept of early health technology assessment, discussed well over a decade, has now been collaboratively implemented by industry, government, and academia to select and expedite the development of emerging technologies that may address the needs of patients and health systems. Early economic evaluation is essential to assess the value of emerging technologies, but empirical data to inform the current practice of early evaluation is limited. We propose a systematic review of early economic evaluation studies in order to better understand the current practice. METHODS/DESIGN: This protocol describes a systematic review of economic evaluation studies of regulated health technologies in which the evaluation is conducted prior to regulatory approval and when the technology effectiveness is not well established. Included studies must report an economic evaluation, defined as the comparative analysis of alternatives with respect to their associated costs and health consequences, and must evaluate some regulated health technology such as pharmaceuticals, biologics, high-risk medical devices, or biomarkers. We will conduct the literature search on multiple databases, including MEDLINE, EMBASE, the Centre for Reviews and Dissemination Databases, and EconLit. Additional citations will be identified via scanning reference lists and author searching. We suspect that many early economic evaluation studies are unpublished, especially those conducted for internal use only. Additionally, we use a chain-referral sampling approach to identify authors of unpublished studies who work in technology discovery and development, starting out with our contact lists and authors who published relevant studies. Citation screening and full-text review will be conducted by pairs of reviewers. Abstracted data will include those related to the decision context and decision problem of the early evaluation, evaluation methods (e.g., data sources, methods, and assumptions used to identify, measure, and value the likely effectiveness and the costs and consequences of the new technology, handling of uncertainty), and whether the study results adequately address the main study question or objective. Data will be summarized overall and stratified by publication status. DISCUSSION: This study is timely to inform early economic evaluation practice, given the international trend in early health technology assessment initiatives.

Novel extraction technique to remove a penile constriction device.

INTRODUCTION: Penile strangulation can be a challenging clinical situation and usually requires prompt treatment. The clinician should be aware of the various techniques to remove such devices. AIM: The aim of this article was to describe a new noninvasive technique, the "pseudo-pulley" method, to remove a penile constriction device. METHODS: During an episode of medication-induced hypersexuality, a 63-year-old man presented to the emergency department with a cast iron locking nut of a vehicle towbar lodged at the base of the patient's penis. RESULTS: The utilization of the "pseudo-pulley" method to remove the constriction device negated the need for more invasive measures. We outline a step-by-step description on this new technique. The patient's recovery was complete and uneventful. CONCLUSION: The current case report describes a noninvasive technique for removing a penile constriction device that does not rely on specialized equipment and industrial drills that can cause iatrogenic injury.

Diet, physical activity, and cardiovascular disease risk factors among older Chinese Americans living in New York City.

Cardiovascular disease (CVD) is the leading cause of death in the US and affects Chinese Americans disproportionately compared to other ethnic groups in the American population. However, few studies have examined CVD risk factors, including diet and physical activity, in Chinese Americans. This investigation used a cross-sectional design to evaluate the dietary intake, dietary supplement use, and physical activity of 125 older Chinese Americans aged 50-98 years, and to determine how these behaviors may be related to obesity and other CVD risk factors. Sociodemographic information, CVD risk factors, dietary intake, and physical activity were obtained from all participants recruited from health fairs conducted in New York City (NYC). The findings revealed that older Chinese American adults living in NYC had a high prevalence of overweight and obesity, borderline hypertension, pre-diabetes, and diabetes. Many participants did not meet their daily requirements calcium, potassium, folate, vitamin B6, and vitamin B12, several minerals and vitamins important for cardiovascular health. Although most participants consumed an adequate numbers of servings of foods from the main food groups, most did not meet the recommended number of servings of dairy foods and only one in four adults took a multivitamin supplement daily. After adjusting for potential confounders, daily consumption of oil/sweets and dairy foods was positively associated with waist circumference. Also, daily consumption of oils/sweets, meats, and grains was positively associated with systolic blood pressure. The majority of the participants reported at least 30 min of moderate intensity physical activity per day. Dietary intake or supplement use did not show protective effects but performing vigorous physical activity may reduce risk of CVD in this population.

Impact of donepezil treatment for Alzheimer's disease on caregiver time.

OBJECTIVE: To assess the impact of donepezil treatment compared with placebo on caregiver time spent assisting patients with Alzheimer's disease (AD). RESEARCH DESIGN AND METHODS: Patient and caregiver data were collected as part of a 1-year, prospective, double-blind, randomized, placebo-controlled trial. The Resource Utilization in Dementia (RUD) questionnaire was used to record caregiver time at study baseline and at Weeks 12, 24, 36, and 52. This analysis focuses solely on those caregivers who were actively (> 0 h/day reported on the RUD) providing care at study baseline. MAIN OUTCOME MEASURES: The change in time relative to baseline that caregivers spent assisting patients over the course of the study. RESULTS: The active caregiver population was composed of 96 caregivers of donepezil-treated patients and 94 caregivers of patients receiving placebo. Over the course of the 1-year study, and as the condition of the AD patients deteriorated, it was expected that caregiver time would increase. As expected, after 52 weeks, caregivers of placebo patients were providing almost 2 h each day (106.8 min) more care than they had done at study baseline. For those caregivers of donepezil-treated patients, although they were spending more time caring than they had done at study baseline, their time burden had only increased by 42.6 min more each day. This difference in caring time between the 2 groups, relative to baseline at Week 52, was 1.1 h (64.2 min) each day, and was significant (p = 0.03). CONCLUSION: Caregiver time devoted to helping an AD patient typically increases with the severity of the disease. By helping the patient maintain his/her ability to perform activities of daily living for longer, treatment with donepezil is not only beneficial to the patient, but also has positive time-burden implications for the caregiver.

An economic evaluation of donepezil in mild to moderate Alzheimer's disease: results of a 1-year, double-blind, randomized trial.

The costs and consequences of donepezil versus placebo treatment in patients with mild to moderate Alzheimer's disease (AD) were evaluated as part of a 1-year prospective, double-blind, randomized, multinational clinical trial. Patients received either donepezil (n = 142; 5 mg/day for 28 days followed by 10 mg/day according to the clinician's judgement) or placebo (n = 144). Unit costs were assessed in 1999 Swedish kronas (SEK) and converted to US dollars (USD). Donepezil-treated patients gained functional benefits relative to placebo on the Progressive Deterioration Scale (p = 0.042) and Instrumental Activities of Daily Living scale (p = 0.025) at week 52. Caregivers of donepezil-treated patients spent an average of 400 h less annually providing care than caregivers of placebo-treated patients. Mean annual healthcare costs were SEK 137,752 (USD 16,438) per patient for the donepezil group and SEK 135,314 (USD 16,147) in the placebo group. With the average annual cost of donepezil at SEK 10,723 (USD 1,280) per patient, the SEK 2,438 (USD 291) cost difference represented a 77% cost offset. When caregiver time and healthcare costs were included, mean annual costs were SEK 209,244 (USD 24,969) per patient in the donepezil group and SEK 218,434 (USD 26,066) in the placebo group, a total saving associated with donepezil treatment of SEK 9,190 (USD 1,097) per patient [95% CI of SEK -43,959 (USD -5,246), SEK 25,581 (USD 3,053); p = 0.6]. The positive effects on the efficacy outcome measures combined with no additional costs from a societal perspective indicate that donepezil is a cost-effective treatment, representing an improved strategy for the management of patients with AD.