Randomised, double-blind, placebo-controlled clinical trial investigating the effects of inorganic nitrate in hypertension-induced target organ damage: protocol of the NITRATE-TOD study in the UK

© 2020 Author(s). Introduction: Arterial stiffness and left ventricular (LV) hypertrophy are the key markers of hypertensive target organ damage (TOD) associated with increased cardiovascular morbidity and mortality. We have previously shown that dietary inorganic nitrate supplementation lowers blood pressure (BP) in hypertension, however, whether this approach might also improve markers of hypertensive TOD is unknown. In this study, we will investigate whether daily dietary inorganic nitrate administration reduces LV mass and improves measures of arterial stiffness. Methods and design: NITRATE-TOD is a double-blind, randomised, single-centre, placebo-controlled phase II trial aiming to enrol 160 patients with suboptimal BP control on one or more antihypertensives. Patients will be randomised to receive 4 months once daily dose of either nitrate-rich beetroot juice or nitrate-deplete beetroot juice (placebo). The primary outcomes are reduction in LV mass and reduction in pulse wave velocity (PWV) and central BP. The study has a power of 95% for detecting a 9 g LV mass change by cardiovascular MRI (∼6% change for a mildly hypertrophied heart of 150 g). For PWV, we have a power of >95% for detecting a 0.6 m/s absolute change. For central systolic BP, we have a>90% power to detect a 5.8 mm Hg difference in central systolic BP. Secondary end points include change in ultrasound flow-mediated dilation, change in plasma nitrate and nitrite concentration and change in BP. Ethics and dissemination: The study was approved by the London - City and East Research Ethics Committee (10/H0703/98). Trial results will be published according to the Consolidated Standards of Reporting Trials statement and will be presented at conferences and reported in peer-reviewed journals

The effect of distractions in the operating room during endourological procedures

Contains fulltext : 98421.pdf (publisher's version ) (Closed access)BACKGROUND: Professionals working in the operating room (OR) are subject to various distractions that can be detrimental to their task performance and the quality of their work. This study aimed to quantify the frequency, nature, and effect on performance of (potentially) distracting events occurring during endourological procedures and additionally explored urologists' and residents' perspectives on experienced ill effects due to distracting factors. METHODS: First, observational data were collected prospectively during endourological procedures in one OR of a teaching hospital. A seven-point ordinal scale was used to measure the level of observed interference with the main task of the surgical team. Second, semistructured interviews were conducted with eight urologists and seven urology residents in two hospitals to obtain their perspectives on the impact of distracting factors. RESULTS: Seventy-eight procedures were observed. A median of 20 distracting events occurred per procedure, which corresponds to an overall rate of one distracting event every 1.8 min. Equipment problems and procedure-related and medically irrelevant communication were the most frequently observed causes of interruptions and identified as the most distracting factors in the interviews. Occurrence of distracting factors in difficult situations requiring high levels of concentration was perceived by all interviewees as disturbing and negatively impacting performance. The majority of interviewees (13/15) thought distracting factors impacted more strongly on residents' compared to urologists' performance due to their different levels of experience. CONCLUSION: Distracting events occur frequently in the OR. Equipment problems and communication, the latter both procedure-related and medically irrelevant, have the largest impact on the sterile team and regularly interrupt procedures. Distracting stimuli can influence performance negatively and should therefore be minimized. Further research is required to determine the direct effect of distraction on patient safety

Do absorption and realistic distraction influence performance of component task surgical procedure?

Background. Surgeons perform complex tasks while exposed to multiple distracting sources that may increase stress in the operating room (e.g., music, conversation, and unadapted use of sophisticated technologies). This study aimed to examine whether such realistic social and technological distracting conditions may influence surgical performance. Methods. Twelve medical interns performed a laparoscopic cholecystectomy task with the Xitact LC 3.0 virtual reality simulator under distracting conditions (exposure to music, conversation, and nonoptimal handling of the laparoscope) versus nondistracting conditions (control condition) as part of a 2 x 2 within-subject experimental design. Results. Under distracting conditions, the medical interns showed a significant decline in task performance (overall task score, task errors, and operating time) and significantly increased levels of irritation toward both the assistant handling the laparoscope in a nonoptimal way and the sources of social distraction. Furthermore, individual differences in cognitive style (i.e., cognitive absorption and need for cognition) significantly influenced the levels of irritation experienced by the medical interns. Conclusion. The results suggest careful evaluation of the social and technological sources of distraction in the operation room to reduce irritation for the surgeon and provision of proper preclinical laparoscope navigation training to increase security for the patient.Industrial DesignIndustrial Design Engineerin

Expression patterns of CEACAM5 and CEACAM6 in primary and metastatic cancers

BACKGROUND: Many breast, pancreatic, colonic and non-small-cell lung carcinoma lines express CEACAM6 (NCA-90) and CEACAM5 (carcinoembryonic antigen, CEA), and antibodies to both can affect tumor cell growth in vitro and in vivo. Here, we compare both antigens as a function of histological phenotype in breast, pancreatic, lung, ovarian, and prostatic cancers, including patient-matched normal, primary tumor, and metastatic breast and colonic cancer specimens. METHODS: Antigen expression was determined by immunohistochemistry (IHC) using tissue microarrays with MN-15 and MN-3 antibodies targeting the A1B1- and N-domains of CEACAM6, respectively, and the MN-14 antibody targeting the A3B3 domain of CEACAM5. IHC was performed using avidin-biotin-diaminobenzide staining. The average score ± SD (0 = negative/8 = highest) for each histotype was recorded. RESULTS: For all tumors, the amount of CEACAM6 expressed was greater than that of CEACAM5, and reflected tumor histotype. In breast tumors, CEACAM6 was highest in papillary > infiltrating ductal > lobular > phyllodes; in pancreatic tumors, moderately-differentiated > well-differentiated > poorly-differentiated tumors; mucinous ovarian adenocarcinomas had almost 3-fold more CEACAM6 than serous ovarian adenocarcinomas; lung adenocarcinomas > squamous tumors; and liver metastases of colonic carcinoma > primary tumors = lymph nodes metastases > normal intestine. However, CEACAM6 expression was similar in prostate cancer and normal tissues. The amount of CEACAM6 in metastatic colon tumors found in liver was higher than in many primary colon tumors. In contrast, CEACAM6 immunostaining of lymph node metastases from breast, colon, or lung tumors was similar to the primary tumor. CONCLUSION: CEACAM6 expression is elevated in many solid tumors, but variable as a function of histotype. Based on previous work demonstrating a role for CEACAM6 in tumor cell migration, invasion and adhesion, and formation of distant metastases (Blumenthal et al., Cancer Res 65: 8809–8817, 2005), it may be a promising target for antibody-based therapy

Clinical Pathways of Third-Line Treatment of Overactive Bladder in the Elderly

Overactive bladder (OAB) is a syndrome of urinary urgency, usually accompanied by frequency, nocturia, and sometimes urinary urgency incontinence. There are many guidelines for the OAB treatment which are constructed on a stepwise fashion starting from the least invasive to the more invasive therapy. The emergence of third-line therapy (AUA/SUFU guidelines) has resulted in significant decrease of more invasive surgery and improved patients’ quality of life. The aim of a clinical pathway is to improve the quality of care, reduce risks, increase patient satisfaction, and increase the efficiency in the use of resources. The available options for the third-line OAB treatments include intravesical injection of botulinum toxin A, percutaneous tibial nerve stimulation (PTNS), and sacral nerve stimulation (SNS). The available evidence confirms that all three treatment approaches are well tolerated and effective, although only botulinum toxin type A (BoNTA) and SNS can achieve nearly a cure of urgency urinary incontinence (UUI). The choice among the different third-line treatment depends on patient preference, availability, and local expertise. The application of these pathways can improve incontinence care by letting physicians adequately communicate with patients and select individualized therapy at an early stage especially for elderly patients