Use In Routine Clinical Practice Research Articles

Computed tomography-derived body composition analysis in patients with advanced cancer: clinical utility and future research.

With weight loss increasingly occurring against a background of obesity across a variety of advanced cancers, there has been increasing interest in computed tomography (CT)-derived body composition analysis. Various imaging software packages and thresholds are commonly in use in CT-derived body composition analysis. This review discusses the current research in field of body composition with emphasis on the information required for such measurements to be taken into routine clinical practice. CT is widely used for tumour staging in patients with cancer. Over the last decade, this imaging modality has been exploited to make measurements of body composition. Using a common landmark (L3) several different thresholds have been developed to stratify adipose and muscle tissue areas according to age, sex and BMI and their relationship with survival. A significant relationship between CT-derived body composition and clinical outcomes has been shown in different tumour types and geographical locations. However, there is considerable variation with methods, thresholds and muscle groups used for analysis. Therefore, there would appear to be a need to develop reliable methodology and population-specific reference ranges to guide clinical interpretation and enable routine clinical use. There has been an explosion of clinical research interest in CT-derived body composition analysis. Such body composition analysis provides important host phenotype information which has prognostic value. For CT-derived body composition to be fit for use in routine clinical practice, there is need for universally accepted terminology, software, muscle group selection, prognostic thresholds to standardize such body composition analysis.

Evaluation of a software for automatic delineation of the mammary gland and organs at risk in patients treated for breast cancer in lateral position

Purpose of the studyThe purpose of this study was to assess the potential for improvement of routine breast and organs at risk contouring in patients treated in the lateral decubitus position using Workflow Box™ (Mirada Medical™, UK) automatic contouring software. Materials and methodsAutomatic contouring of the breast by this software is currently based on an atlas created from isodoses representing 95% of the prescribed dose in a population of patients previously treated at institut Curie. Forty cases of breast cancer (20 right breasts and 20 left breasts) were contoured by three radiation oncologists specialized in breast cancer, allowing the creation of a new atlas in the automatic contouring software. This study assessed the quality of contouring in 20 patients (ten right breasts and ten left breasts) by comparing manual contouring performed by the expert radiation oncologists (reference) with those generated by the old and new atlases developed at Institut Curie. The accuracy of contouring was assessed by overlap volume and the associated standard deviations. ResultsBreast contouring based on the new atlas and by radiation oncologists presented a mean overlap of 0.80±0.09 for the right breast and 0.81±0.06 for the left breast. By comparing volumes of interest contoured by radiation oncologists and those obtained from the old atlas, mean overlap volumes were 0.75±0.08 and 0.74±0.13 for the right and left breasts, respectively. Twenty cases (ten right breasts and ten left breasts) used to create the new atlas were also reprocessed by this same atlas in order to assess the quality of automatic contouring of the breast when the case was already known to the software. The mean overlap volume in this case was 0.84±0.08 for the right breast and 0.83±0.06 for the left breast. Finally, after automatic contouring of organs at risk by means of the new atlas, the mean overlap volume was 0.87±0.04 for the heart and 0.93 for each lung (±0.05 for the right lung and±0.04 for the left lung). ConclusionWorkflow Box™ automatic contouring software, based on our new atlas provides reliable and clinically relevant organs at risk and breast contouring. The contours proposed by the software from the new atlas were better than those obtained with the previous atlas based on 95% isodoses obtained from old treatment plans. This software has therefore become more efficient, justifying its use in routine clinical practice for breast cancer contouring in patients treated in the lateral decubitus position. Investigations are currently underway to develop a fully automated process to ensure reliable, robust and operator-independent contouring and breast cancer treatment dosimetry in the lateral decubitus position. Promising preliminary results have already been obtained.

The first experience with the fully-covered self-expandable nitinol stents in the management of anastomotic biliary strictures after orthotopic liver transplantation

Background: Biliary anastomosis strictures after orthotopic liver transplantation (OLT) develop in 5–12% of patients. This complication significantly impairs the patients’ quality of life and can lead to graft loss.Aim: To analyze the first experience in the use of coated self-expanding nitinol stents in patients with biliary anastomosis strictures after OLT.Materials and methods: From December 2018 to January 2019, there were 5 patients with anastomotic strictures after OLT in the Department of Organ and/or Tissue Transplantation of the S.P. Botkin Municipal Clinical Hospital. All patients underwent endoscopic stenting of strictures with a self-expanding nitinol-coated stent. In all patients, the stent was removed at 3 months after its placement.Results: No complications and deaths were recorded in this patient group. The median duration of the follow-up after stent removal was 14.15 ± 2.35 (3–17) months, with no cases of restenosis identified.Conclusion: The use of coated nitinol stents in the management of patients with anastomotic strictures after liver transplantation is effective and safe. The possibility of their use in routine clinical practice requires confirmation in further studies.

Terminology for describing normally sited and ectopic pregnancies on ultrasound: ESHRE recommendations for good practice.

STUDY QUESTIONWhat recommendations can be provided to improve terminology for normal and ectopic pregnancy description on ultrasound?SUMMARY ANSWERThe present ESHRE document provides 17 consensus recommendations on how to describe normally sited and different types of ectopic pregnancies on ultrasound.WHAT IS KNOWN ALREADYCurrent diagnostic criteria stipulate that each type of ectopic pregnancy can be defined by clear anatomical landmarks which facilitates reaching a correct diagnosis. However, a clear definition of normally sited pregnancies and a comprehensive classification of ectopic pregnancies are still lacking.STUDY DESIGN, SIZE, DURATIONA working group of members of the ESHRE Special Interest Group in Implantation and Early Pregnancy (SIG-IEP) and selected experts in ultrasound was formed in order to write recommendations on the classification of ectopic pregnancies.PARTICIPANTS/MATERIALS, SETTING, METHODSThe working group included nine members of different nationalities with internationally recognised experience in ultrasound and diagnosis of ectopic pregnancies on ultrasound. This document is developed according to the manual for development of ESHRE recommendations for good practice. The recommendations were discussed until consensus by the working group, supported by a survey among the members of the ESHRE SIG-IEP.MAIN RESULTS AND THE ROLE OF CHANCEA clear definition of normally sited pregnancy on ultrasound scan is important to avoid misdiagnosis of uterine ectopic pregnancies. A comprehensive classification of ectopic pregnancy must include definitions and descriptions of each type of ectopic pregnancy. Only a classification which provides descriptions and diagnostic criteria for all possible locations of ectopic pregnancy would be fit for use in routine clinical practice. The working group formulated 17 recommendations on the diagnosis of the different types of ectopic pregnancies on ultrasound. In addition, for each of the types of ectopic pregnancy, a schematic representation and examples on 2D and 3D ultrasound are provided.LIMITATIONS, REASONS FOR CAUTIONOwing to the limited evidence available, recommendations are mostly based on clinical and technical expertise.WIDER IMPLICATIONS OF THE FINDINGSThis document is expected to have a significant impact on clinical practice in ultrasound for early pregnancy. The development of this terminology will help to reduce the risk of misdiagnosis and inappropriate treatment.STUDY FUNDING/COMPETING INTEREST(S)The meetings of the working group were funded by ESHRE. T.T. declares speakers’ fees from GE Healthcare. The other authors declare that they have no conflict of interest.TRIAL REGISTRATION NUMBERN/ADISCLAIMERThis Good Practice Recommendations (GPR) document represents the views of ESHRE, which are the result of consensus between the relevant ESHRE stakeholders and where relevant based on the scientific evidence available at the time of preparation. ESHRE’s GPRs should be used for informational and educational purposes. They should not be interpreted as setting a standard of care or be deemed inclusive of all proper methods of care nor exclusive of other methods of care reasonably directed to obtaining the same results. They do not replace the need for application of clinical judgement to each individual presentation, nor variations based on locality and facility type. Furthermore, ESHRE’s GPRs do not constitute or imply the endorsement, recommendation or favouring of any of the included technologies by ESHRE.

Additive effectiveness and feasibility of a theory-driven instant assessment and feedback system in brief cannabis intervention: A randomised controlled trial

Assessment and personalised feedback are important components of brief interventions (BIs) for cannabis use. A key outcome is to increase motivation to change during this short interaction. The diversity of available assessments and time burden scoring them pose a challenge for routine use in clinical practice. An instant assessment and feedback (iAx) system was developed to administer assessments informed by bioSocial Cognitive Theory, that were instantly scored and benchmarked against clinical norms, to provide patient feedback and guide treatment planning. This study evaluated the feasibility and additive effectiveness of the iAx on motivation to change cannabis use, when compared to treatment as usual (TAU), in a single-session BI. A randomised controlled trial was conducted in a public hospital alcohol and drug outpatient clinic. Eighty-seven cannabis users (Mage = 26.41; 66% male) were assigned to the BI utilising the iAx (iAx; n = 44) or to the standard BI (TAU; n = 43). Patients completed pre- and post-BI assessments of motivation to change and a post-BI measure of treatment satisfaction. Practitioners completed a feedback survey. Patients receiving iAx reported a significantly greater increase in motivation to change from pre- to post-BI compared to patients receiving TAU (d = 0.49, p = .03). Treatment satisfaction was high across both conditions, with no significant difference between groups (p = .57). Practitioners also reported a high level of satisfaction with the iAx system. In summary, findings support the feasibility and additive effectiveness of the iAx to enhance patient motivation during cannabis BI.

Urinary Biomarkers for Diagnosis and Prediction of Acute Kidney Allograft Rejection: A Systematic Review.

Noninvasive tools for diagnosis or prediction of acute kidney allograft rejection have been extensively investigated in recent years. Biochemical and molecular analyses of blood and urine provide a liquid biopsy that could offer new possibilities for rejection prevention, monitoring, and therefore, treatment. Nevertheless, these tools are not yet available for routine use in clinical practice. In this systematic review, MEDLINE was searched for articles assessing urinary biomarkers for diagnosis or prediction of kidney allograft acute rejection published in the last five years (from 1 January 2015 to 31 May 2020). This review follows the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Articles providing targeted or unbiased urine sample analysis for the diagnosis or prediction of both acute cellular and antibody-mediated kidney allograft rejection were included, analyzed, and graded for methodological quality with a particular focus on study design and diagnostic test accuracy measures. Urinary C-X-C motif chemokine ligands were the most promising and frequently studied biomarkers. The combination of precise diagnostic reference in training sets with accurate validation in real-life cohorts provided the most relevant results and exciting groundwork for future studies.

The clinical characterization of the adult patient with depression aimed at personalization of management.

Depression is widely acknowledged to be a heterogeneous entity, and the need to further characterize the individual patient who has received this diagnosis in order to personalize the management plan has been repeatedly emphasized. However, the research evidence that should guide this personalization is at present fragmentary, and the selection of treatment is usually based on the clinician's and/or the patient's preference and on safety issues, in a trial-and-error fashion, paying little attention to the particular features of the specific case. This may be one of the reasons why the majority of patients with a diagnosis of depression do not achieve remission with the first treatment they receive. The predominant pessimism about the actual feasibility of the personalization of treatment of depression in routine clinical practice has recently been tempered by some secondary analyses of databases from clinical trials, using approaches such as individual patient data meta-analysis and machine learning, which indicate that some variables may indeed contribute to the identification of patients who are likely to respond differently to various antidepressant drugs or to antidepressant medication vs. specific psychotherapies. The need to develop decision support tools guiding the personalization of treatment of depression has been recently reaffirmed, and the point made that these tools should be developed through large observational studies using a comprehensive battery of self-report and clinical measures. The present paper aims to describe systematically the salient domains that should be considered in this effort to personalize depression treatment. For each domain, the available research evidence is summarized, and the relevant assessment instruments are reviewed, with special attention to their suitability for use in routine clinical practice, also in view of their possible inclusion in the above-mentioned comprehensive battery of measures. The main unmet needs that research should address in this area are emphasized. Where the available evidence allows providing the clinician with specific advice that can already be used today to make the management of depression more personalized, this advice is highlighted. Indeed, some sections of the paper, such as those on neurocognition and on physical comorbidities, indicate that the modern management of depression is becoming increasingly complex, with several components other than simply the choice of an antidepressant and/or a psychotherapy, some of which can already be reliably personalized.

Validation of the Pneumocystis pneumonia score in haematology patients with acute respiratory failure

BackgroundPneumocystis pneumonia (PCP) is an important cause of acute respiratory failure (ARF) in immunocompromised patients, yet no actual clinical tool suitably identifies patients at risk. Recently, a multivariable prediction model has been proposed for haematology patients with ARF requiring intensive care unit (ICU) admission to assess the risk of PCP (PCP score). However, it has not yet been validated externally.MethodsTo validate the PCP score, a retrospective cohort study was conducted in two large designated haematology centres in Korea. One-hundred and forty haematology patients with ARF were admitted to ICU. They underwent aetiologic evaluations between July 2016 and June 2019. The predictive ability of the score was assessed with the receiver operating characteristic (ROC) curve analysis for both the discrimination and calibration of the score.ResultsAmong the 141 patients, 13 (9.2%) were finally diagnosed of PCP. Although the median of PCP score in PCP group was higher than in non-PCP group (3.0 [interquartile range 0.0–4.0] vs. 2.0 [0.5–4.0]), the difference was not statistically significant (P = 0.679). The area under the ROC curve of the PCP score in our cohort was 0.535 (95% CI, 0.449–0.620), indicating no discriminatory ability. When using a cut-off of 3.0 the score, the result was 38.5% (95% CI, 13.9–68.4) sensitive and 7.03% (95% CI, 61.6–78.1) specific. The negative predictive value was 58.8% and positive predictive value was 59.8% for a 10% prevalence of PCP.ConclusionsIn this study, the PCP score was not useful to predict the risk of PCP in haematology patients with ARF. Further prospective validation studies are needed to validate the score’s use in routine clinical practice for the early diagnosis of PCP in haematology patients.

Optimal Management of Allergic Fungal Rhinosinusitis.

IntroductionAllergic fungal rhinosinusitis (AFRS) is a chronic disorder with significant morbidity and a high recurrence rate needing long-term follow-up. Even after its first description many decades ago, there is still considerable uncertainty about the management of this condition.DescriptionIn this chapter, we breakdown the topic “Optimal management of allergic fungal rhinosinusitis” into sub-headings in order to discuss the latest research and available literature under each topic in great detail. Every attempt has been made to incorporate the highest level of evidence that was available at the time of writing.SummaryPre-operative diagnosis and further management prior to surgery is important. Steroids help in reducing inflammation and help improve the surgical field. Surgery remains the mainstay in the management of this condition along with long-term medical management. Oral steroids are reserved for acute flare-ups in the background of associated lung concerns. Oral and topical antifungal agents have no role in the control of the disease. Biological agents are being prescribed predominantly by respiratory physician colleagues, mainly for the control of the chest-related issues rather than for sinus disease. Immunotherapy as an adjunct with surgery is promising.ConclusionAFRS is a disease with many variables and a wide range of symptomatic presentation. It takes a keen clinician to identify the disease and subsequently manage the condition. Treatment involves long-term follow-up with early detection of recurrence or flare-ups. Any of the mentioned modalities of management may be employed to effectively control the condition, and treatment protocols will have to be tailor-made to suit each individual patient. Various medications and drugs such as Manuka honey, antimicrobial photodynamic therapy, hydrogen peroxide and betadine rinses appear to be promising. More robust studies need to be undertaken to ascertain their routine use in clinical practice.

Drug induced liver injury: an update.

Drug induced liver injury (DILI) is a relatively rare hepatic condition in response to the use of medications, illegal drugs, herbal products or dietary supplements. It occurs in susceptible individuals through a combination of genetic and environmental risk factors believed to modify drug metabolism and/or excretion leading to a cascade of cellular events, including oxidative stress formation, apoptosis/necrosis, haptenization, immune response activation and a failure to adapt. The resultant liver damage can present with an array of phenotypes, which mimic almost every other liver disorder, and varies in severity from asymptomatic elevation of liver tests to fulminant hepatic failure. Despite recent research efforts specific biomarkers are not still available for routine use in clinical practice, which makes the diagnosis of DILI uncertain and relying on a high degree of awareness of this condition and the exclusion of other causes of liver disease. Diagnostic scales such as the CIOMS/RUCAM can support the causality assessment of a DILI suspicion, but need refinement as some criteria are not evidence-based. Prospective collection of well-vetted DILI cases in established DILI registries has allowed the identification and validation of a number of clinical variables, and to predict a more severe DILI outcome. DILI is also in need of properly designed clinical trials to evaluate the efficacy of new DILI treatments as well as older drugs such as ursodeoxycholic acid traditionally used to ameliorate cholestasis or corticosteroids now widely tried in the oncology field to manage the emergent type of hepatotoxicity related to immune checkpoint inhibitors.

Critical Evaluation of the 2017 Classification of Periodontal and Peri-implant diseases and Conditions – An Update

Periodontal disease is the multifactorial disease that leads to the destruction of the tooth-supporting structures. A classification system provides a framework that helps in diagnosis and assembles similar disease phenotypes in a more homogeneous form. Several classifications have been proposed by many authors. Till date, the American Academy of Periodontology (AAP) 1999 Classification was the most extensively used classification, which was designed to overcome the drawbacks and deficiencies of the 1989 classification. However, presence of some drawbacks has limited its use in routine clinical practice. So, the current classification has been developed in 2017 by AAP and the European Federation of Periodontology (EFP) to overcome the disadvantages of the 1999 classification. The 2017 classification is extremely extensive and more intricate than 1999 classification, which is useful to the overall dentist and periodontists to select the best treatment options for the patients. This review summarizes the newer classification, key changes from 1999 Classification/modification and disadvantages of the newer classification.

AD-Related CSF Biomarkers Across Distinct Levels of Cognitive Impairment: Correlations With Global Cognitive State

Associations between cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) with the severity of cognitive impairment are unclear. We examined the correlations between CSF biomarkers and cognitive performance in the AD continuum. We studied 143 elderly patients: cognitively unimpaired (n = 51), mild cognitive impairment (MCI) amnestic (n = 55) and nonamnestic (n = 20), and mild AD (n = 17) assessed with the Cambridge Cognitive Test (CAMCOG). We correlated total CAMCOG and its subdomains with CSF Aβ42, T-tau, p-tau levels, and Aβ42/p-tau. In the total sample, T-tau and Aβ42/p-tau correlated with the total CAMCOG (P < .01); all biomarkers correlated with memory (P < .001); T-tau correlated with language (P < .01). Memory and T-tau levels may be the most suitable parameters to reflect cognitive/CSF biomarker correlations. At present, such correlations are of little use in routine clinical practice.

ACG Clinical Guidelines: Clinical Use of Esophageal Physiologic Testing.

Esophageal symptoms are common and may indicate the presence of gastroesophageal reflux disease (GERD), structural processes, motor dysfunction, behavioral conditions, or functional disorders. Esophageal physiologic tests are often performed when initial endoscopic evaluation is unrevealing, especially when symptoms persist despite empiric management. Commonly used esophageal physiologic tests include esophageal manometry, ambulatory reflux monitoring, and barium esophagram. Functional lumen imaging probe (FLIP) has recently been approved for the evaluation of esophageal pressure and dimensions using volumetric distension of a catheter-mounted balloon and as an adjunctive test for the evaluation of symptoms suggestive of motor dysfunction. Targeted utilization of esophageal physiologic tests can lead to definitive diagnosis of esophageal disorders but can also help rule out organic disorders while making a diagnosis of functional esophageal disorders. Esophageal physiologic tests can evaluate obstructive symptoms (dysphagia and regurgitation), typical and atypical GERD symptoms, and behavioral symptoms (belching and rumination). Certain parameters from esophageal physiologic tests can help guide the management of GERD and predict outcomes. In this ACG clinical guideline, we used the Grading of Recommendations Assessment, Development and Evaluation process to describe performance characteristics and clinical value of esophageal physiologic tests and provide recommendations for their utilization in routine clinical practice.

Rationale and design of a European epidemiological post-authorization safety study (PASS) program: rivaroxaban use in routine clinical practice

ABSTRACT Background Rivaroxaban is a highly selective factor Xa inhibitor approved for use in Europe for multiple indications. Study design and methods The European rivaroxaban epidemiological post-authorization safety study (PASS) program consists of seven complementary observational studies. For four of the studies, data are obtained from health-care databases in the UK, the Netherlands, Germany, and Sweden. These database studies describe patterns of rivaroxaban use and patient characteristics over time, and investigate safety and effectiveness outcomes in new users of rivaroxaban using a cohort analysis and nested case–control analysis. To put these results in context, safety outcomes are also analyzed in new users of standard of care. In addition, a modified prescription event monitoring study conducted in the early post-launch phase in primary care, and two specialist cohort event monitoring studies that investigated rivaroxaban use in the secondary care hospital setting, systematically collected drug utilization and safety data via questionnaires completed by health-care professionals in the UK. Discussion The European rivaroxaban epidemiological PASS is a comprehensive program of complementary studies generating evidence from patients treated in routine clinical practice that will expand our understanding of the risk–benefit profile of rivaroxaban.

Adaptation of the prostate biopsy collaborative group risk calculator in patients with PSA less than 10ng/ml improves its performance.

The prostate biopsy collaborative group risk calculator (PBCGRC) is a newly developed risk estimator for predicting prostate biopsy outcomes. However, its clinical usefulness is still unknown within the so-called gray area of PSA values. This study aimed to determine whether updating the PBCGRC improves its predictive performance for predicting any-grade and high-grade (HG), defined as biopsy Gleason score ≥ 7, prostate cancer (PCa) in patients with prostate-specific antigen (PSA) less than 10ng/ml. The risk of any-grade and HGPCa was calculated using the PBCG risk calculation formulas updated by recalibration in the large, logistic recalibration and model revision. Predictive performances of the PBCGRC and the updated models were compared using discrimination, calibration, and clinical utility. Within the study sample of 526 patients, PCa was detected in 193 (36.7%), and 78 (14.8%) of them had HGPCa. According to the calibration curves, the PBCGRC overestimated the risk of PCa. Predictive accuracy of the revised model was higher [the area under the receiver-operating characteristic curve (AUCs), 65.4% and 70.2%] than that of the PBCGRC (AUCs, 60.4% and 64.3%) for any-grade and HGPCa. The net benefit was greater for model revision in comparison with the original model. The performance accuracy of PBCGRC for the prediction of any and HGPC in men undergoing prostate biopsy with PSA levels below 10ng/ml is suboptimal. The model revision resulted with significant improvement in model performance. However, external validation of the revised model is necessary before its routine use in clinical practice.

Optical imaging technology in colonoscopy: Is there a role for photometric stereo?

Colonoscopy screening for the detection and removal of colonic adenomas is central to efforts to reduce the morbidity and mortality of colorectal cancer. However, up to a third of adenomas may be missed at colonoscopy, and the majority of post-colonoscopy colorectal cancers are thought to arise from these. Adenomas have three-dimensional surface topographic features that differentiate them from adjacent normal mucosa. However, these topographic features are not enhanced by white light colonoscopy, and the endoscopist must infer these from two-dimensional cues. This may contribute to the number of missed lesions. A variety of optical imaging technologies have been developed commercially to enhance surface topography. However, existing techniques enhance surface topography indirectly, and in two dimensions, and the evidence does not wholly support their use in routine clinical practice. In this narrative review, co-authored by gastroenterologists and engineers, we summarise the evidence for the impact of established optical imaging technologies on adenoma detection rate, and review the development of photometric stereo (PS) for colonoscopy. PS is a machine vision technique able to capture a dense array of surface normals to render three-dimensional reconstructions of surface topography. This imaging technique has several potential clinical applications in colonoscopy, including adenoma detection, polyp classification, and facilitating polypectomy, an inherently three-dimensional task. However, the development of PS for colonoscopy is at an early stage. We consider the progress that has been made with PS to date and identify the obstacles that need to be overcome prior to clinical application.

New technical approach to the diabetes therapy.

Optimal glycemic control remains challenging in individuals with type 1 diabetes. With the comprehensive clinical evidence on safety and efficiency, the adoption of continuous glucose monitoring (CGM), insulin pumps, and control algorithms merging the two into closed-loop systems is rapidly increasing. Particularly the CGM and intermittently scanned CGM improved diabetes management outcomes in large populations. A meaningful translation from clinical trials in highly controlled settings to numerous evaluations of closed-loop technology in the unrestricted home environment ended with its commercialization and use in routine clinical practice. Although it is still not a cure, the closed-loop currently seems to be the most promising advancement in the treatment of diabetes, with promising results also reported from routine clinical practice in children and adults with type 1 diabetes. We summarize different aspects of a technological approach to diabetes care, list currently available devices and systems in the pipeline, and the key supporting clinical evidence for their use. We consider human factors associated with technology use and the importance of health economics to support implementation and reimbursement.

New developments in von Willebrand disease.

Von Willebrand disease (VWD) constitutes the most common inherited human bleeding disorder. It is associated with a mucocutaneous bleeding phenotype that can significantly impact upon quality of life. Despite its prevalence and associated morbidity, the diagnosis and subclassification of VWD continue to pose significant clinical challenges. This is in part attributable to the fact that plasma von Willebrand factor (VWF) levels vary over a wide range in the normal population, together with the multiple different physiological functions played by VWF in vivo. Over recent years, substantial progress has been achieved in elucidating the biological roles of VWF. Significant advances have also been made into defining the pathophysiological mechanisms underpinning both quantitative and qualitative VWD. In particular, several new laboratory assays have been developed that enable more precise assessment of specific aspects of VWF activity. In the present review, we discuss these recent developments in the field of VWD diagnosis, and consider how these advances can impact upon clinical diagnostic algorithms for use in routine clinical practice. In addition, we review some important recent advances pertaining to the various treatment options available for managing patients with VWD.

Promoting medication adherence from the perspective of adolescent and young adult kidney transplant recipients, parents, and health care professionals: A TAKE-IT TOO study.

Medication non-adherence is an important factor limiting allograft survival after kidney transplantation in AYA. Some interventions, including the TAKE-IT, showed some success in promoting adherence but the potential for scalability and use in routine clinical practice is limited. We applied user-centered design to gather the perspectives of recipients, parents, and health professionals concerning their needs, challenges, and potential intervention strategies to design an optimal, multi-component medication adherence intervention. The qualitative study was conducted at four Canadian and three American kidney transplant programs. Separate focus groups for recipients, parents, and health professionals were convened to explore these stakeholders' perspectives. Directed content analysis was employed to identify themes that were shared vs distinct across stakeholders. All stakeholder groups reported challenges related to taking medications on time in the midst of their busy schedules and the demands of transitioning toward independence during adolescence. The stakeholders also made suggestions for the multi-component behavioral intervention, including an expanded electronic pillbox and companion website, education materials, and customized digitized features to support shared responsibility and communication among recipients, parents, and health professionals. Several suggestions regarding the functionality and features of the potential intervention reported in this early stage will be explored in more depth as the iterative process unfolds. Our approach to actively involve all stakeholders in the process increases the likelihood of designing an adherence intervention that is truly user-informed and fit for the clinical setting.

A randomized trial of the electronic Lung Cancer Symptom Scale for quality-of-life assessment in patients with advanced non-small-cell lung cancer.

Improving health-related quality of life (hrqol) is a key goal of systemic therapy in advanced lung cancer, although routine assessment remains challenging. We analyzed the impact of a real-time electronic hrqol tool, the electronic Lung Cancer Symptom Scale (elcss-ql), on palliative care (pc) referral rates, patterns of chemotherapy treatment, and use of other supportive interventions in patients with advanced non-small-cell lung cancer (nsclc) receiving first-line chemotherapy. Patients with advanced nsclc starting first-line chemotherapy were randomized to their oncologist receiving or not receiving their elcss-ql data before each clinic visit. Patients completed the elcss-ql at baseline, before each chemotherapy cycle, and at subsequent follow-up visits until disease progression. Prospective data about the pc referral rate, hrqol, and use of other supportive interventions were collected. For the 95 patients with advanced nsclc who participated, oncologists received real-time elcss-ql data for 44 (elcss-ql arm) and standard clinical assessment alone for 51 (standard arm). The primary endpoint, the pc referral rate, was numerically higher, but statistically similar, for patients in the elcss-ql and standard arms. The hrqol scores over time were not significantly different between the two study arms. The elcss-ql is feasible as a tool for use in routine clinical practice, although no statistically significant effect of its use was demonstrated in our study. Improving access to supportive care through the collection of patient-reported outcomes and hrqol should be an important component of care for patients with advanced lung cancer.