The Harris hip score: Do ceiling effects limit its usefulness in orthopedics?: A systematic review

The Harris hip score (HHS), a disease-specific health status scale that is frequently used to measure the outcome of total hip arthroplasty, has never been validated properly. A questionnaire is suitable only when all 5 psychometric properties are of sufficient quality. We questioned the usefulness of the HHS by investigating its content validity. We performed a systematic review based on a literature search in PubMed, Embase, and the Cochrane Library for descriptive studies published in 2007. 54 studies (59 patient groups) met our criteria and were included in the data analysis. To determine the content validity, we calculated the ceiling effect (percentage) for each separate study and we pooled data to measure the weighted mean. A subanalysis of indications for THA was performed to differentiate the populations for which the HHS would be suitable and for which it would not. A ceiling effect of 15% or less was considered to be acceptable. Over half the studies (31/59) revealed unacceptable ceiling effects. Pooled data across the studies included (n = 6,667 patients) suggested ceiling effects of 20% (95%CI: 18-22). Ceiling effects were greater (32%, 95%CI:12-52) in those patients undergoing hip resurfacing arthroplasty. Although the Harris hip score is widely used in arthroplasty research on outcomes, ceiling effects are common and these severely limit its validity in this field of researc

Spatiotemporal regulation of clonogenicity in colorectal cancer xenografts

Cancer evolution is predominantly studied by focusing on differences in the genetic characteristics of malignant cells within tumors. However, the spatiotemporal dynamics of clonal outgrowth that underlie evolutionary trajectories remain largely unresolved. Here, we sought to unravel the clonal dynamics of colorectal cancer (CRC) expansion in space and time by using a color-based clonal tracing method. This method involves lentiviral red-green-blue (RGB) marking of cell populations, which enabled us to track individual cells and their clonal outgrowth during tumor initiation and growth in a xenograft model. We found that clonal expansion largely depends on the location of a clone, as small clones reside in the center and large clones mostly drive tumor growth at the border. These dynamics are recapitulated in a computational model, which confirms that the clone position within a tumor rather than cell-intrinsic features, is crucial for clonal outgrowth. We also found that no significant clonal loss occurs during tumor growth and clonal dispersal is limited in most models. Our results imply that, in addition to molecular features of clones such as (epi-)genetic differences between cells, clone location and the geometry of tumor growth are crucial for clonal expansion. Our findings suggest that either microenvironmental signals on the tumor border or differences in physical properties within the tumor, are major contributors to explain heterogeneous clonal expansion. Thus, this study provides further insights into the dynamics of solid tumor growth and progression, as well as the origins of tumor cell heterogeneity in a relevant model system

DNA damage-induced PARP1 activation confers cardiomyocyte dysfunction through NAD(+) depletion in experimental atrial fibrillation

Atrial fibrillation (AF) is the most common clinical tachyarrhythmia with a strong tendency to progress in time. AF progression is driven by derailment of protein homeostasis, which ultimately causes contractile dysfunction of the atria. Here we report that tachypacing-induced functional loss of atrial cardiomyocytes is precipitated by excessive poly(ADP)-ribose polymerase 1 (PARP1) activation in response to oxidative DNA damage. PARP1-mediated synthesis of ADP-ribose chains in turn depletes nicotinamide adenine dinucleotide (NAD+), induces further DNA damage and contractile dysfunction. Accordingly, NAD+ replenishment or PARP1 depletion precludes functional loss. Moreover, inhibition of PARP1 protects against tachypacing-induced NAD+ depletion, oxidative stress, DNA damage and contractile dysfunction in atrial cardiomyocytes and Drosophila. Consistently, cardiomyocytes of persistent AF patients show significant DNA damage, which correlates with PARP1 activity. The findings uncover a mechanism by which tachypacing impairs cardiomyocyte function and implicates PARP1 as a possible therapeutic target that may preserve cardiomyocyte function in clinical AF

STARD 2015: An Updated List of Essential Items for Reporting Diagnostic Accuracy Studies.

Incomplete reporting has been identified as a major source of avoidable waste in biomedical research. Essential information is often not provided in study reports, impeding the identification, critical appraisal, and replication of studies. To improve the quality of reporting of diagnostic accuracy studies, the Standards for Reporting of Diagnostic Accuracy Studies (STARD) statement was developed. Here we present STARD 2015, an updated list of 30 essential items that should be included in every report of a diagnostic accuracy study. This update incorporates recent evidence about sources of bias and variability in diagnostic accuracy and is intended to facilitate the use of STARD. As such, STARD 2015 may help to improve completeness and transparency in reporting of diagnostic accuracy studies

Appropriateness, Reasons and Independent Predictors of Consultations in the Emergency Department (ED) of a Dutch Tertiary Care Center: A Prospective Cohort Study.

OBJECTIVE:Consultations occur frequently in the emergency department (ED) of tertiary care centres and pose a threat for patient safety as they contribute to ED lengths of stay (LOS) and overcrowding. The aim of this study was to investigate reasons and appropriateness of consultations, and the relative impact of specialty and patient characteristics on the probability of a consultation, because this could help to improve efficiency of ED patient care. METHODS:This prospective cohort study included ED patients presenting to a Dutch tertiary care centre in a setting where ED physicians mostly treat self-referred and undifferentiated patients and other specialists treat referred patients. Consultations were defined as appropriate if the reason of consultation corresponded with the final advice, conclusion or policy of the consulted specialty. Multivariable logistic regression analysis was used to assess the relative contribution of specialty and patient characteristics on consultation. RESULTS:In the 344 (24% (95% CI 22 to 26%)) of the 1434 inclusions another specialty was consulted, resulting in a 55% increase of ED LOS. ED physicians more often consulted another specialty with a corrected odds ratio (OR) of 5.6 (4.0 to 7.8), mostly because consultations were mandatory in case of hospitalization or outpatient follow-up. Limited expertise of ED physicians was the reason for consultation in 7% (5 to 9%). The appropriateness of consultations was 84% (81 to 88%), similar between ED physicians and other specialists (P = 0.949). The patient characteristics age, comorbidity, and triage category and complaint predicted consultation. CONCLUSION:In a Dutch tertiary care centre another specialty was consulted in 24% of the patients, mostly for an appropriate reason, and rarely because of lack of expertise. The impact of consultations on ED LOS could be reduced if mandatory consultations are abolished and predictors of a consultation are used to facilitate timely consultation

Multivariable logistic regression analysis to predict consultation.

<p>Multivariable logistic regression analysis to predict consultation.</p

Appropriateness of none mandatory consultations.

<p>Appropriateness of none mandatory consultations.</p

Input, throughput and output flow diagram of included patients.

<p>Patients treated by the ED physician are depicted in white, and those treated by the other specialties in grey. The boxes with dashed lines present patients that received no consultation or multidisciplinary approach. When the lines are closed, patients received one or multiple consultations. One patient was admitted to the ward without being treated by any physician. In 1 patients the final disposition was unknown. Six patients had another final disposition as depicted, of whom 5 had died on the ED and 1 returned to the psychiatric hospital were the patient was admitted before arrival at the ED.</p