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A Comprehensive And Practical Guide To Clinical...


Endometriosis-associated pain (EAP) has a significant impact on the quality of life of those affected and their families. Recognizing that endometriosis is a chronic condition associated with an impairment in function and negative social impact, there is a shift toward reducing diagnostic delays and initiating timely management. This article provides a comprehensive and practical approach to the clinical diagnosis of EAP, which can subsequently facilitate prompt and directed treatment. The key components of the history, physical examination, and high-quality imaging to evaluate suspected EAP and related pain conditions are presented. Currently, biomarkers have limited utility in the diagnosis of endometriosis, but research in this area continues; development of a reliable noninvasive test for endometriosis may further improve early identification of this condition.




A Comprehensive and Practical Guide to Clinical...


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Noninvasive biomarkers are needed to monitor stable patients following kidney transplantation (KT), as subclinical rejection, currently detectable only with invasive surveillance biopsies, can lead to chronic rejection and graft loss. Several biomarkers have recently been developed to detect rejection in KT recipients, using different technologies as well as varying clinical monitoring strategies defined as "context of use (COU)." The various metrics utilized to evaluate the performance of each biomarker can also vary, depending on their intended COU. As the use of molecular biomarkers in transplantation represents a new era in patient management, it is important for clinicians to better understand the process by which the incremental value of each biomarkers is evaluated to determine its potential role in clinical practice. This process includes but is not limited to an assessment of clinical validity and utility, but to define these, the clinician must first appreciate the trajectory of a biomarker from bench to bedside as well as the regulatory and other requirements needed to navigate this course successfully. This overview summarizes this process, providing a framework that can be used by clinicians as a practical guide in general, and more specifically in the context of subclinical rejection following KT. In addition, we have reviewed available as well as promising biomarkers for this purpose in terms of the clinical need, COU, assessment of biomarker performance relevant to both the need and COU, assessment of biomarker benefits and risks relevant to the COU, and the evidentiary criteria of the biomarker relevant to the COU compared with the current standard of care. We also provide an insight into the path required to make biomarkers commercially available once they have been developed and validated so that they used by clinicians outside the research context in every day clinical practice.


Since the first scRNA-seq study was published in 2009 [5], there has been increasing interest in conducting such studies. Perhaps one of the most compelling reasons for doing so is that scRNA-seq can describe RNA molecules in individual cells with high resolution and on a genomic scale. Although scRNA-seq studies have been conducted mostly by specialist research groups over the past few years [5,6,7,8,9,10,11,12,13,14,15,16], it has become clear that biomedical researchers and clinicians can make important new discoveries using this powerful approach as the technologies and tools needed for conducting scRNA-seq studies have become more accessible. Here, we provide a practical guide for biomedical researchers and clinicians who might wish to consider performing scRNA-seq studies.


The Psychiatric Assessment Form was designed to assist health care workers perform comprehensive psychiatric assessments and screening for major mental illnesses. It should be used by individuals with some understanding of the interview process and the signs and symptoms of psychiatric disorders. Though research comparing the use of this interview tool to others has not yet been performed, both residents and medical students who have used it note its ease of use and comprehensiveness. We believe that this guide to the psychiatric interview may be particularly effective for interns, residents, medical students, and nursing staff in inpatient and outpatient psychiatric settings.


Based on group discussions, review of included papers on this topic, and our personal experience in analysing results of randomised clinical trials, we here present a practical guide with flowcharts on how to deal with missing data when analysing results of randomised clinical trials. We divide our presentation into two sections, of which one is concerned with the planning stage of a randomised clinical trial, while the other focuses on analytical approaches which may prevent bias caused by missing data. We describe the most valid methods used to handle MAR data and proper use of sensitivity analyses to handle MNAR data.


Handling missing data validly is an important, yet difficult and complex, task. We have presented practical flowcharts on how to deal with missing data when analysing results of randomised clinical trials. It is beyond the scope of this paper to describe how to deal with the multiple and often very complex statistical issues when, for example, using multiple imputation. It is often advisable to consult knowledgeable persons with statistical expertise when analysing trial results, and this paper does not in any way change this need. However, we have presented a practical guide and an overview of the steps that always need to be considered during the analysis stage of a trial.


Management of the frail older individual is challenging on multiple levels. Understanding of frailty has increased dramatically over the past decade, thanks to research into the biological basis of frailty and methods to define and predict the syndrome. There is no firm consensus, however, on how to assess and diagnose frailty in the clinical setting [3]. Care of frail individuals is also difficult, due to complex comorbidities, vulnerability to deterioration and increased social needs [1, 4], compounded by the need for consistent ongoing management despite frequently fragmented health service delivery. A practical, evidence-based guide for clinicians is therefore needed.


Unexplained exertional dyspnoea or fatigue can arise from a number of underlying disorders and shows only a weak correlation with resting functional or imaging tests. Noninvasive cardiopulmonary exercise testing (CPET) offers a unique, but still under-utilised and unrecognised, opportunity to study cardiopulmonary and metabolic changes simultaneously. CPET can distinguish between a normal and an abnormal exercise response and usually identifies which of multiple pathophysiological conditions alone or in combination is the leading cause of exercise intolerance. Therefore, it improves diagnostic accuracy and patient health care by directing more targeted diagnostics and facilitating treatment decisions. Consequently, CPET should be one of the early tests used to assess exercise intolerance. However, this test requires specific knowledge and there is still a major information gap for those physicians primarily interested in learning how to systematically analyse and interpret CPET findings. This article describes the underlying principles of exercise physiology and provides a practical guide to performing CPET and interpreting the results in adults.


CPET provides an objective and reproducible opportunity to identify why an individual is complaining of exertional dyspnoea and to quantify the limitation of exercise capacity. It can help not only to differentiate between pulmonary, pulmonary vascular and cardiovascular disease but also to unmask the underlying and often complex mechanisms. Accordingly, CPET should be performed before the patient undergoes extensive diagnostic workup that searches in a state of rest for an abnormality that takes place during exercise. CPET probably covers a broader range of potential differential diagnoses than any other test in medicine and is also likely to be cost effective because it directs diagnosis and facilitates treatment decisions [1]. Moreover, many patients regard CPET as being a very useful part of their clinical examination [24]. This all suggests that CPET should be used much more frequently, particularly since the expenditure of time, e.g., compared to exercise ECG, is low in routine use. In addition, the diagnostic value of CPET significantly exceeds that of non-discriminating tests of exercise performance (exercise ECG, 6-min walking test, etc. that provide no information about exercise tolerance), because prognostically important key variables can be determined with the simultaneous measurement of ventilatory gas exchange, even at submaximal exercise levels. However, this global cardiopulmonary reference test is increasingly at risk of disappearing from outpatient specialist medical care for a variety of reasons, such as cost, lack of expertise or reimbursement [15]. This inconsistency is partly explained by the fact that CPET statements may be considered complicated and often fail to provide practical, easy-to-follow guidance [6]. CPET can be seen as a complex test (based on the unique wealth of information it provides) but not necessarily a difficult tool that can be performed well by non-specialists. However, lack of a compact and readily accessible introduction for those interested in learning how to analyze and interpret CPET findings might limit wider use of this powerful reference method. Accordingly, CPET should be promoted in the clinical setting and training should be a mandatory component of respiratory specialist medical training. In this regard, the exemplified CPET standard operating procedure of the German Centre for Cardiovascular Research recommends the initial guided application of 5 CPETs and the subsequent independent performance and interpretation of at least 20 CPETs under supervision [37]. Although this introduction is not intended to be comprehensive, we have attempted to provide a practical guide for those involved in the performance and interpretation of CPET, and to encourage the use of this specialist reference examination much more frequently in indicated cases. 041b061a72


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