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Laser Doppler imaging is universally considered the most evidence-based method for objective burn depth assessment by accurately predicting burn wound healing potential. This study has analyzed how exactly laser Doppler imaging measurements can be useful in the early therapeutic decision making for patients with clinically indeterminate depth burns.An extensive survey, by questionnaire and in-depth interviews, was conducted among 51 burn centers worldwide to gain insight on the practical use of laser Doppler imaging.Twenty-seven (53%) of the 51 burn centers contacted almost completely answered the 32 questions. Fifty-two percent of these centers (14/27) had at least 10 years of laser Doppler imaging experience. laser Doppler imaging was considered to be mainly or almost completely accurate by 89%. In case of discrepancy between clinical assessment and LDI, 41% relied more on clinical diagnosis, 25% delayed decision to operate, while 16% re-scanned the next day. The centers most experienced with laser Doppler imaging (13%) relied on it more. Final decisions for treatment were based on the combination of laser Doppler imaging and clinical assessment by 74%. Seventy percent of the centers almost never operated burns with laser Doppler imaging-red and would almost always operate burns with LDI-blue. Treatment decisions for intermediate laser Doppler imaging colors (pink, yellow and green) varied, with 76% basing decisions on other factors: % Total Body Surface Area (TBSA), general health, age, location of the burn, potential for colonization/infection, patient preference, compliance with aftercare, logistics, and socio-economic factors.Laser Doppler imaging reduces the number of clinical indeterminate depth burns. For these intermediate depth burns on laser Doppler imaging, treatment decisions are based on a combination of interpretation ('man') and laser Doppler imaging measurements ('machine'). Thorough knowledge of confounding factors and validated laser Doppler imaging color code, consideration of surrounding laser Doppler imaging colors, the use of mean flux values, and not directly burn related factors are essential. Burn centers with most laser Doppler imaging experience considered laser Doppler imaging an indispensable diagnostic tool.

Brain metastases (BM) present a common cause of mortality and morbidity in several metastatic cancer entities. New therapeutic developments during the last decades, including targeted and immune-related therapies, have shown considerable extra- and intracranial response rates in specific subgroups of BM patients. However, differences in the molecular alteration in the BM tumor tissue compared to extracranial tumors leads to heterogeneous therapeutic responses. Therefore, an accurate molecular analyzation of BM tissue, if possible, has become an essential part in therapeutic decision making in BM patients. The concordance of predictive molecular biomarkers between multiple sites including extracranial and intracranial tumor tissue have been analyzed for some but not all biomarkers routinely applied in modern precision medicine approaches. In the present review, we summarize the current evidence of predictive biomarkers for personalized therapy approaches in the treatment of parenchymal BM.

Modern hyperacute reperfusion therapies including intravenous thrombolysis and mechanical thrombectomy have transformed the management of arterial ischemic stroke (AIS) in adults. Multiple randomized clinical trials have demonstrated that these therapies enable remarkable improvements in clinical outcome for properly selected patients with AIS. Because pediatric patients were excluded from predicate clinical trials, there is a conspicuous lack of data to guide selection of therapies and inform age-adjusted and pathology-oriented treatment modifications for children. Specifically, technical guidance concerning treatment eligibility, drug dosing, and device implementation is lacking. This review aims to outline important features that differentiate pediatric AIS from adult AIS and provide practical strategies that will assist the stroke specialist with therapeutic decision making.

The frontline treatment paradigm for patients with advanced or metastatic non-small cell lung cancer (NSCLC) has changed dramatically in the past decade amid efforts to tackle this leading cause of cancer-related mortality. Immune checkpoint inhibitors (ICIs) targeting the programmed cell death protein 1 (PD-1) receptor and its ligand PD-L1 are an important therapeutic option for patients whose tumors lack genetic alterations that dictate response to molecularly targeted therapies. With a growing number of FDA-approved ICI monotherapy and combination therapy options for first-line therapy, the use of biomarkers such as PD-L1 expression has become increasingly important in guiding therapeutic decision making. Presently, PD-L1 expression remains a key biomarker in this setting, in spite of its limitations. This article will evaluate the current and evolving clinical trends in the use of ICIs in the frontline management of metastatic NSCLC, as well as the challenges associated with PD-L1 expression analysis and biomarker implementation.

BACKGROUND AND AIMS Therapeutic, clinical trial entry and stratification decisions for hepatocellular carcinoma (HCC) are made based on prognostic assessments, using clinical staging systems based on small numbers of empirically selected variables that insufficiently account for differences in biological characteristics of individual patients' disease. APPROACH AND RESULTS We propose an approach for constructing risk scores from circulating biomarkers that produce a global biological characterization of individual patient's disease. Plasma samples were collected prospectively from 767 patients with HCC and 200 controls, and 317 proteins were quantified in a Clinical Laboratory Improvement Amendments-certified biomarker testing laboratory. We constructed a circulating biomarker aberration score for each patient, a score between 0 and 1 that measures the degree of aberration of his or her biomarker panel relative to normal, which we call HepatoScore. We used log-rank tests to assess its ability to substratify patients within existing staging systems/prognostic factors. To enhance clinical application, we constructed a single-sample score, HepatoScore-14, which requires only a subset of 14 representative proteins encompassing the global biological effects. Patients with HCC were split into three distinct groups (low, medium, and high HepatoScore) with vastly different prognoses (medial overall survival 38.2/18.3/7.1 months; P

FAST is essential to decide whether trauma patients need laparotomy, but it has a notable decrease in accuracy in patients with pelvic fracture. Our objective is to analyze the consequences of therapeutic decision-making based on the FAST results in trauma patients with pelvic fracture.Descriptive study that includes trauma patients older than 16 with a pelvic fracture admitted to the critical care area or who died. The FAST result was compared with a true positive or negative value according to the results of laparotomy or abdominal CT. We recorded diagnosis and treatment of each injury and resolution of the case, detailing the cause of death, among all variables.Over the 13-year period, we included 263 trauma patients with pelvic fracture, with a mean ISS of 31 and mortality of 19%. FAST had a sensitivity of 65.2%, specificity of 69%, false negative rate of 34.8% and false positive rate of 30.9%. Hemodynamically unstable patients died twice as many stable patients (27% vs 14%, P .05). Patients with positive FAST died more than negative FAST (43% vs 26%); and 4 out of 10 hemodynamically unstable patients who underwent non-therapeutic laparotomy after presenting a false positive FAST died from hypovolemic shock. The mortality rate fell from 60% to 20% when preperitoneal packing was performed before angio-embolization of the pelvis.FAST has low accuracy in polytraumatized patients with pelvic fracture. Patients with false positive FAST have higher mortality, which can be reduced notably by applying preperitoneal packing.

Relapsing multiple sclerosis (RMS) presents a highly variable clinical evolution among patients, and its management should be personalized. Although there is no cure at present, effective disease-modifying therapies (DMTs) are available. Selection of the most appropriate DMT for each patient is influenced by several clinical, radiological and demographic aspects as well as personal preferences that, at times, are not covered in the regulatory criteria. This may be a source of difficulty, especially in certain situations where so-called ‘high-efficacy DMTs’ (usually considered second-line) could be of greater benefit to the patient. In this narrative review, we discuss evidence and experience, and propose a pragmatic guidance on decision-making with respect to the indication and management of high-efficacy DMT in adult patients with RMS based on expert opinion.

These recommendations, produced by a group of Canadian retina experts, have been developed to assist both retina specialists and general ophthalmologists in the management of vision-threatening neovascular age-related macular degeneration (nAMD). The recommendations are based on published evidence as well as collective experience and expertise in routine clinical practice. We provide an update on practice principles for optimal patient care, focusing on identified imaging biomarkers, in particular retinal fluid, as well as current and emerging therapeutic approaches. Algorithms for delivering high-quality care and improving long-term patient outcomes are provided, with an emphasis on timely and appropriate treatment to preserve and maintain vision. In the context of nAMD, increasing macular fluid or leakage on fluorescein angiography (FA) may indicate disease activity regardless of its location. Early elimination of intraretinal fluid (IRF) is of particular relevance as it is a prognostic indicator of worse visual outcomes. Robust referral pathways for second opinion and peer-to-peer consultations must be in place for cases not responding to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy.

Background Implementation of personalized medicine requires the accessibility of tumor molecular profiling in order to allow prioritization of appropriate targeted therapies for individual patients. Our aim was to study the role of comprehensive genomic profiling assays that may inform treatment recommendations for patients with solid tumors. Materials and Methods We performed a prospective study to evaluate the feasibility of application of the FoundationOne CDx panel—which detects substitutions, insertions and deletions, and copy number alterations in 324 genes, select gene rearrangements, and genomic signatures including microsatellite instability and tumor mutation burden (TMB)—to patients with advanced or recurrent solid tumors before its approval in Japan. Results A total of 181 samples were processed for genomic testing between September 2018 and June 2019, with data being successfully obtained for 175 of these samples, yielding a success rate of 96.7%. The median turnaround time was 41 days (range, 21–126 days). The most common known or likely pathogenic variants were TP53 mutations (n = 113), PIK3CA mutations (n = 33), APC mutations (n = 32), and KRAS mutations (n = 29). Among the 153 patients assessed for TMB, the median TMB was 4 mutations/Mb, and tumors with a high TMB (≥10 mutations/Mb) were more prevalent for lung cancer (11/32) than for other solid tumor types (9/121, Fisher's exact test p < .01). No clear trend toward increased efficacy for immune checkpoint inhibitor (ICI) monotherapy or ICI combination chemotherapy in patients with a high programmed cell death–ligand 1 tumor proportion score or a high TMB was apparent. Among the 174 patients found to harbor known or likely pathogenic actionable alterations, 24 individuals (14%) received matched targeted therapy. Conclusion The FoundationOne CDx assay was performed with formalin‐fixed, paraffin‐embedded tumor specimens with a success rate of >95%. Such testing may inform the matching of patients with cancer with investigational or approved targeted drugs. Implications for Practice This prospective cohort study was initiated to investigate the feasibility and utility of clinical application of FoundationOne CDx. A total of 181 samples were processed for genomic testing between September 2018 and June 2019, with data being successfully obtained for 175 of these samples, yielding a success rate of 96.7%, and 24 individuals (14%) received matched targeted therapy., Comprehensive genomic profiling assays can identify multiple actionable genetic alterations that may inform treatment recommendations for patients with solid tumors. This article evaluates the feasibility of the application of the FoundationOne CDx panel to patients with advanced or recurrent solid tumors.

Purpose: The primary origin of neuroendocrine tumor metastases can be difficult to determine by histopathology alone, but is critical for therapeutic decision making. DNA methylation–based profiling is now routinely used in the diagnostic workup of brain tumors. This has been enabled by the availability of cost-efficient array-based platforms. We have extended these efforts to augment histopathologic diagnosis in neuroendocrine tumors. Experimental Design: Methylation data was compiled for 69 small intestinal, pulmonary, and pancreatic neuroendocrine tumors. These data were used to build a ridge regression calibrated random forest classification algorithm (neuroendocrine neoplasm identifier, NEN-ID). The model was validated during 3 × 3 nested cross-validation and tested in a local and an external cohort (n = 198 cases). Results: NEN-ID predicted the origin of tumor samples with high accuracy (>95%). In addition, the diagnostic approach was determined to be robust across a range of possible confounding experimental parameters, such as tumor purity and array quality. A software infrastructure and online user interface were built to make the model available to the scientific community. Conclusions: This DNA methylation–based prediction model can be used in the workup for patients with neuroendocrine tumors of unknown primary. To facilitate validation and clinical implementation, we provide a user-friendly, publicly available web-based version of NEN-ID.

Although atopic dermatitis (AD) classically presents as eczematous, pruritic plaques in the flexural regions of children, AD can present with several morphologies and distributions that may vary wi...

Venous thromboembolism associated with COVID-19, particularly acute pulmonary embolism, may represent a challenging and complex clinical scenario. The benefits of having a multidisciplinary pulmonary embolism response team (PERT) can be important during such a pandemic. The aim of PERT in the care of such patients is to provide fast, appropriate, multidisciplinary, team-based approach, with the common goal to tailor the best therapeutic decision making, prioritizing always optimal patient care, especially given lack of evidence-based clinical practice guidelines in the setting of COVID-19, which potentially confers a significant prothrombotic state. Herein, we would like to briefly emphasize the importance and potential critical role of PERT in the care of patients in which these two devastating illnesses are present together.

Bladder cancer is a heterogenous disease that is associated with tangible mortality in muscle invasive disease. The WHO 2016 classification of urothelial tumours reflects the contemporary approach towards histological variants in bladder cancer, including variants of urothelial carcinoma (UC) and non-urothelial variants. This review focuses on variant histology in UC, and discusses the importance of accurate histological diagnosis, and subsequent risk stratification and therapeutic decision making based on proper variant recognition. Most urothelial variants are associated with poorer outcomes compared to conventional UC, although some perform reasonably better. However, high quality evidence detailing optimal treatment and survival outcomes are still lacking in literature, due to the rarity of these cases.

Background and purpose Therapeutic decision-making is a critical part of the skill set required by practicing pharmacists. A potentially straightforward way to teach and evaluate decision-making skills is use of real-time simulations. This study aimed to evaluate pharmacy students' perceptions of using a real-time simulation game to treat their own virtual patient. Educational activity and setting Second professional year (Y2) and fourth professional year (Y4) pharmacy students were provided an opportunity to use a virtual patient simulation in their courses. Student perceptions of the game and use of the game for decision-making were evaluated by a questionnaire. The qualitative findings were analysed using an inductive thematic analysis. Findings The questionnaire was completed by 120 Y2 and 115 Y4 students. Four themes arose from the analysis that reflected the students' perceptions of autonomy in their learning and practice, the difficulty in committing to a decision, and having fun while learning. Summary This work provides an initial exploration of the perceptions of pharmacy students about playing a real-time, autonomous, simulation-based game for treating a patient. Future research should focus on more detailed evaluation of this game for learning therapeutic decision-making.

The recent changes in curricula in veterinary medicine have changed the delivery and focus on veterinary pharmacology and therapeutics, resulting in a perceived lack of knowledge of pharmacology and therapeutic decision making in recent graduates. To aid veterinary pharmacologists and clinicians teaching clinical pharmacology, core competencies were drafted by a working group. Following this process, a Delphi study was performed to come to a consensus on day-1 competencies in veterinary pharmacology and therapeutics. The described competencies could be useful to a variety of stakeholders in veterinary pharmacology, including those teaching veterinary pharmacology worldwide. Secondly, they could form the basis of vertical alignment of the subject within schools and across the world, as well as serving to frame the integration of veterinary pharmacology and therapeutics into competency-based veterinary education.

Objectives To evaluate the association between low disease activity according to the new ASDAS nomenclature and the physician therapeutic decisions in patients with axial spondyloarthritis (axSpA). Material and Methods Longitudinal retrospective study including patients diagnosed with axSpA receiving a tumor necrosis factor-inhibitor between January 2014 and June 2019 as a first treatment. For each visit, disease activity was determined afterwards according to the new ASDAS nomenclature (inactive, low, high and very high activity), and the physician's therapeutic decision was recorded. The association between disease activity and the physician's decision was evaluated through descriptive statistics. Results A total of 304 visits of 104 patients with axSpA were analyzed. For those visits where a low activity ASDAS score was obtained, the physician's therapeutic decision was no escalation of treatment in 98.2 % of cases. However, for those visits with a high or very high disease activity ASDAS score, the physician's therapeutic decision was to escalate treatment in 33.7 % and 82.8 % of cases respectively. Conclusions The state measured by the ASDAS index formerly defined as ‘moderated disease activity’ is considered in clinical practice as ‘low disease activity’ because of the physician's choice in these situations to not-escalate the treatment. Our data substantiate the recent updating in ASDAS nomenclature.

Introduction To improve therapeutic decision making, it is crucial that information regarding adverse drug reactions reaches patients. It is not enough to disseminate such findings through regulatory and scientific channels; targeted efforts to reach patients are necessary. One possible avenue is to collaborate with patient organizations. Objectives The aim of this pilot study was to explore how adverse drug reactions can be communicated through patient organizations. Methods A text describing a signal of levothyroxine and panic attacks was tailored to patients’ needs, in terms of language, style and content, with emphasis placed on what to do when experiencing the symptoms described. The signal was communicated via the Dutch thyroid organization’s digital newsletter, social media channels, website and print magazine. Results The digital newsletter was distributed to around 5000 subscribers. On Facebook, 13,820 people viewed the message, with 2346 clicks in the message, indicating an intention to read the whole post. The interactions on social media were positive, and the tone was respectful. Conclusion Patient organizations can help enable effective communication of adverse drug reactions to a relevant audience. The social media post generated more engagement than other communications from the patient organization, indicating a strong interest in this information. The additional patient experiences that were shared in the comments on social media further strengthened the original signal and its relevance to patients, creating an interesting feedback loop. The favourable experiences in this study support further consideration and exploration of this approach to communicate adverse drug reactions to patients.

Introduction Regular physical activity (PA) is recommended by all type 2 diabetes mellitus (T2DM) management guidelines. The OPADIA study aimed to determine whether using a specific patient questionnaire (Optima-PA©) could help T2DM patients increase their PA by leading to better physician-patient communication and improved levels of shared decision making concerning Specific, Measurable, Acceptable, Realistic, Timely (SMART)-PA micro-objectives. Methods Physicians participating in this multicentre, prospective, randomised, real-life study were allocated to a standard group (T2DM patients managed according to usual clinical practice, n = 24) or the OPTIMA-PA group (additional use of the questionnaire, n = 30). The main outcome was the percentage of inclusion visits ending with the setting up of at least one SMART-PA micro-objective. Other outcomes were the impact of the OPTIMA-PA questionnaire on patient perceptions of shared decision making (ENTRED questionnaire) and the impact of the OPTIMA-PA questionnaire and establishing SMART-PA micro-objectives as well as patient-perceived physician empathy (ENTRED questionnaire) and GP aptitude for patient-centredness (SEPCQ scores) on patient PA levels over a 3-month period (IPAQ-SF scores). Results One hundred twenty-two patients were included in the standard group and 134 in the OPTIMA-PA group. Unexpectedly, more inclusion visits ended with SMART-PA micro-objectives being set up in the standard group (p

Objective To evaluate the use of WhatsApp as a clinical tool and determine the perception of orthopaedic surgeons of its usefulness. Material and methods Orthopaedic surgeons attending a scientific meeting were invited to complete an anonymous and structured survey on the use of the application in the clinical setting. Results A total of 41 (38%) surveys were correctly completed. Of the respondents, 100% had been either senders or receivers of clinical information via the application. Ninety-three per-cent had used the application to consult in relation to a clinical case. Of the respondents, 78% belonged to a WhatsApp group in which clinical information is shared: 71% agreed that communication between clinicians through WhatsApp is a useful tool for making therapeutic decisions. Conclusion The use of WhatsApp for clinical purposes by orthopaedic surgeons is widespread. Most consider it a useful tool in therapeutic decision making.

Sepsis is one of the oldest and most elusive syndromes in medicine that is still incompletely understood. Biomarkers may help to transform sepsis from a physiologic syndrome to a group of distinct biochemical disorders. This will help to differentiate between systemic inflammation of infectious and noninfectious origin and aid therapeutic decision making, hence improve the prognosis for patients, guide antimicrobial therapy, and foster the development of novel adjunctive sepsis therapies. To reach this goal requires increased systematic investigation that includes twenty-first century scientific approaches and technologies and appropriate clinical evaluation.

Summary In recent decades, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis has transformed from an almost uniformly fatal disease to a treatable form of primary systemic vasculitis. Substantial disease heterogeneity exists within ANCA-associated vasculitis and the increasing understanding of this heterogeneity has implications for guiding treatment decisions. Approaches to induction and maintenance therapy vary depending on disease severity, clinical manifestations, and patient-specific factors. In this narrative Review, we examine how disease heterogeneity in ANCA-associated vasculitis, with respect to disease severity, clinical presentations, and ANCA specificity, influences therapeutic decision making. Many questions regarding therapeutic strategies in ANCA-associated vasculitis remain unanswered, and these should guide future research in this complex group of diseases.

Since its introduction to the diagnostic pathway for prostate cancer management, prostate-specific membrane antigen (PSMA)–ligand PET has demonstrated great potential. PSMA-ligand imaging is increasingly influencing therapeutic decision making, although its impact on patient outcomes still needs to be defined. One relatively new application, enabled through chemical and engineering efforts, is PSMA-guided surgery. This review highlights the potential of PSMA-guided surgery and discusses its implications in lymph node dissection in primary and recurrent prostate cancer.

Therapeutic options for metastatic CRC (mCRC) have changed significantly in recent years, greatly increasing the complexity of therapeutic decision-making. Although oncology guidelines have helped improve the care process, guidelines may also limit the flexibility to individualize in-clinic decision-making. This consensus paper addresses specific gaps in the current international guidelines to assist Taiwanese colon and rectal experts make specific therapeutic choices. Over 3 years and three meetings with selected experts on “real-world” Taiwanese practice patterns for mCRC, consensus was achieved. The experts also discussed specific questions during in-depth one-on-one consultation. Outcomes of the discussion were then correlated with published evidence by an independent medical writer. The final consensus includes clinically implementable recommendations to provide guidance in treating Taiwanese mCRC patients. The consensus includes criteria for defining fit and unfit intensive treatment patients, treatment goals, treatment considerations of molecular profiles, treatment consideration, and optimal treatment choices between different patient archetypes, including optimal treatment options based on RAS, BRAF, and microsatellite instability (MSI) status. This consensus paper is the second in the Taiwan Society of Colon and Rectal Surgeons (TSCRS) Consensus series to address unmet gaps in guideline recommendations in lieu of Taiwanese mCRC management. Meticulous discussions with experts, the multidisciplinary nature of the working group, and the final drafting of the consensus by independent medical professionals have contributed to the strong scientific value of this consensus.

Background: Despite clear indications for intervention, therapeutic decision-making for elderly patients with severe symptomatic aortic stenosis (AS) remains a complex issue due to the wide variation in individual risk profiles and the involvement of patients' subjective preferences. We aimed to investigate the reasons leading to the decisions against intervention and the consequences thereof on survival.Methods: Data were derived from the China Elderly Valve Disease (China-DVD) Cohort Study on patients aged ≥60-year-old with severe symptomatic AS consecutively enrolled between September to December 2016. Patients were analyzed according to the initial therapeutic decisions made by consensus between patients and physicians at the time of the index evaluation: intervention group (patients who were evaluated as suitable for intervention and accepted the treatment proposal); patient-refusal group (patients who were evaluated as suitable for intervention but refused due to subjective preferences); physician-deny group (patients who were denied intervention by physicians after evaluation). The least absolute shrinkage and selection operator (LASSO)-penalized logistic regression model was used to identify the factors associated with physicians' decisions against intervention. Twelve-month survival was analyzed using Cox proportional hazards models, with multivariate adjustment using inverse probability weighting (IPW).Results: Among the enrolled 456 elderly patients with severe symptomatic AS, 52 (11.4%) patients refused intervention and 49 (10.7%) patients were denied intervention by their physicians. LASSO-penalized logistic regression model identified that reduced left ventricular ejection fraction and increased EuroSCORE-II were strongly associated with physicians' decisions against intervention. At 12-month follow-up, only 8 (15.4%) patients who initially refused the intervention proposal underwent the subsequent intervention, with an average delay of 195 days. Patients' initial decisions against intervention were significantly associated with 12-month mortality, even after IPW adjustment (Hazard ratio: 2.61; 95% confidence interval: 1.09–6.20; P = 0.031).Conclusions: The decision against intervention was taken in about one-fifth of elderly patients with symptomatic severe AS, half of which were due to patients' subjective preferences. Surgical risk remains the primary concern for physicians when making therapeutic decisions. Elderly patients' initial decisions against intervention have a profound impact on subsequent intervention rates and prognosis, and therefore should be treated as a “risk factor” at the subjective level.Clinical Trial Registration:clinicaltrials.gov/ct2/show/NCT02865798, China elDerly Valve Disease (China-DVD) cohort study (NCT02865798).

Infection-induced acute encephalopathy 3 (IIAE3) is an autosomal dominant disease resulting from a pathogenic variant in the RANBP2 gene. IIAE3 results in the susceptibility to the recurrence of acute necrotizing encephalopathy (ANE1) which presents as bilateral symmetric thalamic, midbrain and/or hindbrain lesions that typically develops within 1-4 days post-acute viral infection, commonly occurring before age 6.1-6 These case reports highlight a retrospective analysis of clinical data and radiographic studies on 2 ANE1 cases from our institution. The novel p.Leu450Phe variant of the RANBP2 gene was analyzed using in silico algorithms (PolyPhen-2, SIFT, Mutationtaster) which suggests the p.Leu450Phe variant is probably deleterious.7 An expansion of documented ANE1 case presentations and clinically significant RANBP2 gene mutations has the potential to improve long term outcomes if more informed therapeutic decision making can be achieved.

Objective: To evaluate the impact of cone-beam computed tomography (CBCT) in endodontic therapeutic decision-making of immature traumatized teeth with suspected pulp necrosis. Methods: Over two years, consecutive patients with a dental trauma in their front teeth (apex >0.5 mm) and with suspected pulp necrosis based on clinical and radiographic findings were referred to a specialist clinic in Sweden. Fifteen patients aged 6–13 (18 teeth) were included and clinically examined by an endodontist. Intraoral radiographs and CBCT examinations were obtained. Five practitioners, three endodontists and two residents in endodontics, used these examinations to determine the most appropriate treatment for the 18 cases (all central incisors) on two occasions scheduled 19 weeks apart. On the first occasion, the practitioners had access to clinical information and the intraoral radiographs (‘before’ CBCT); on the second occasion, the practitioners had also access to a radiologist report and the CBCT images (‘after’ CBCT). Their treatment plans – no treatment, watchful waiting, endodontic orthograde treatment, or extraction – were made anonymously and independently. Results were analysed using descriptive statistics and Wilcoxon signed-rank test. Results: ‘After’ CBCT, practitioners changed treatment plans in 30% of the 90 assessments, 74% of which were more aggressive (p = 0.028). In 49% of the assessments, practitioners who chose the watchful and waiting treatment plan ‘before’ CBCT changed to a more aggressive therapy such as endodontic orthograde treatment and extraction ‘after’ CBCT (p = 0.005). Conclusion: This study provides evidence that CBCT influences endodontic therapeutic decision-making regarding immature traumatised teeth with suspected pulp necrosis, chiefly when expectant management (i.e., watchful and waiting) was selected before access to CBCT.

Purpose: Genomic signatures, such as EndoPredict®, may help clinicians to decide which adjuvant treatment is the most appropriate. Methods: We propose the EndoPredict® assay for unclear cases of adjuvant treatment in patients treated in our comprehensive cancer center. We prospectively and retrospectively report the decision of adjuvant treatment before and after the EndoPredict® assay, respectively, compared to the PREDICT’s tool scores. Results: From November 2016 to March 2019, 159 breast cancer tumors were analyzed and presented before and after the EndoPredict® assay. Before the EndoPredict® results, clinicians recommended chemotherapy for 57 patients (57/159, 36%). A total of 108 patients (108/159, 68%) were classified as EPclin high-risk score. There was only a slight agreement between clinicians’ decisions and EPclin risk score. The EPclin score led to 37% changes in treatment (59/159); chemotherapy was favored in 80% of cases (47/59). The PREDICT tool recommended chemotherapy for 16 high-risk patients (16/159, 10%). Conclusion: Although genomic tests were developed in order to de-escalate adjuvant treatment, in our comprehensive cancer center the use of the EndoPredict® assay led to an increase in prescribed chemotherapy.

Objective. The ability of pharmacy students to self-regulate and reflect on knowledge and skills is important as proficient self-assessment skills guide learning strategies and prompt students to bridge their knowledge gaps. The objectives for this study were to determine how well third-year pharmacy students self-assess, explore the rationales behind their self-assessments and determine whether there is a correlation between self-assessment accuracy and academic performance. Methods. A quasi-experimental one-group pre-/post-test design was conducted with third-year pharmacy students. Examiner grades, student self-assessment grades, comparative reports, and end-of-semester grades were collected. Students were categorized into tertiles based on academic performance for data analysis. Paired t tests, Pearson r and percentage agreements were conducted to investigate self-assessment accuracy. Correlational statistical tests were implemented to examine the relationships between self-assessment accuracy and academic performance. Results. One hundred sixty-two third-year pharmacy students were included. On average, students demonstrated poor self-evaluation skills and underestimated themselves by 4.9%. Lower performing students were generally overconfident in evaluating their performance. There was no significant correlation between students’ self-assessment accuracy and academic performance on the subsequent end-of-semester examination questions. Conclusion. Overall, students tended to underestimate their academic performance. Further research on self-assessment is needed to better understand how students think about their performance, which may help to improve education methods, such as inclusion of reflective practices after case-based activities.

Background and Purpose— Therapeutic decision making for small unruptured intracranial aneurysms ( Methods— We analyzed 338 small unruptured aneurysms; 35 ruptured during the observation period, and 303 remained stable. Clinical, morphological, and hemodynamic parameters were considered. Computational fluid dynamics was used to calculate hemodynamic parameters based on computed tomography images of all aneurysms in their unruptured state. Differences between the ruptured and unruptured groups were tested by the Mann-Whitney U or Fisher exact tests. Multivariate logistic regression was applied to obtain a rupture risk model. Its predictive ability was investigated by receiver operating characteristic analysis. Results— The risk model revealed that rupture may be more likely to in younger patients (odds ratio [OR], 0.92 for each age increase of 1 year [95% CI, 0.88−0.96] P P =0.03), located at a bifurcation (OR, 5.45 [95% CI, 1.87−15.85] P =0.002), with a bleb (OR, 4.09 [95% CI, 1.42−11.79] P =0.009), larger length (OR, 1.91 for each increase of 1 mm [95% CI, 1.42−2.57] P P =0.01). The sensitivity, specificity, and area under the curve were 0.800, 0.752, and 0.826 (95% CI, 0.739−0.914) respectively. Conclusions— Younger age, presence of multiple aneurysms, location at a bifurcation, presence of a bleb, larger length, and lower pressure loss coefficient were identified as risk factors for rupture of small intracranial aneurysms. The risk model should be validated in further studies.

Drs. Tan and Nunes carefully interpret the results of this study [(1)][1] toward potential impact on subsequent therapeutic decision making. As pointed out correctly, the contemporary pathophysiologic concept of secondary mitral regurgitation (sMR) identifies 2 key mechanisms, each of which might

Novel cardiac mapping systems allow a safe and highly accurate 3-D reconstruction of cardiac structures as well as fast and accurate visualization of cardiac arrhythmias. In addition, they are increasingly reducing the need for fluoroscopy in these procedures. The current state of the art, as well as the presentation of possible uses of individual systems and their limitations, is presented in this article. Cardiac mapping systems can significantly contribute to an optimal therapeutic decision making in invasive electrophysiology. This article introduces new developments of Rhythmia, Topera, EnSite Precision, and CARTO systems and provides a look ahead to the future.

Active surveillance trials for low-risk ductal carcinoma in situ (DCIS) are in progress in the United States and Europe. In some of these trials, the presence of comedo necrosis in the DCIS has been an exclusion criterion for trial entry. However, the minimum amount of necrosis required by pathologists for a diagnosis of comedo necrosis is not well-defined. We surveyed 35 experienced breast pathologists to assess their diagnostic threshold for comedo necrosis. Pink circles representing necrosis ranging in extent from 10 to 80% of the duct diameter were superimposed on eight replicate histologic images of a single duct involved by low nuclear grade, solid pattern DCIS. These images were circulated by e-mail to the participating pathologists who were asked to select the image that represents the minimum amount of necrosis that they require for a diagnosis of comedo necrosis. Among the 35 participants, the minimum extent of the duct diameter required for a diagnosis of comedo necrosis was 10% for 4 pathologists, 20% for 5, 30% for 11, 40% for 7, 50% for 6, 60% for 1 and 70% for 1. There was no single threshold about which more than one-third of the pathologists agreed met the minimal criteria for comedo necrosis. We conclude that even among experienced breast pathologists, the threshold for comedo necrosis is highly variable. Our findings highlight the need for a standardized definition of comedo necrosis as a trial criterion, and more generally where it may be used as a marker of increased risk of recurrence for therapeutic decision making.

According to the Centers for Disease Control and Prevention, the rate of breastfeeding in the United States has increased 34% between 2005 and 2015. Women who breastfeed can require treatment of various common illnesses. When caring for women who are breastfeeding, health care providers may unnecessarily discourage them from breastfeeding during treatment. Choosing the appropriate medications for these individuals is critical to ensure the woman is effectively treated, infant exposure to medication is minimized, and the breastfeeding relationship is preserved. This article provides an overview of essential principles for prescribing medications for women who are lactating. Recommendations for the management of common illnesses seen in the outpatient setting are suggested and resources that can help guide therapeutic decision making are offered.

The incidence of prosthetic shoulder replacements has increased considerably in recent years, as well as the complications derived from the procedure. The correct diagnosis of each type of complication is essential for therapeutic decision making, which is currently based on the information provided by radiological and nuclear medicine imaging. Nevertheless, both techniques have intrinsic limitations that could be mostly overcome with the advent of the hybrid SPECT/CT imaging, which is set to play a fundamental role in the evaluation of shoulder prostheses.

In clinical practice cardiac involvement in patients with storage disorders is often diagnosed at a late and advanced stage of the disease with pronounced organ damage. As the currently available targeted therapies can only stop the progress of the disease, a timely diagnosis is of particular relevance. Genetic testing has become increasingly more important in cases of suspected cardiac manifestation in storage disorders. Thereby, diagnostic genetic testing can help to confirm the diagnosis and may also be relevant for therapeutic decision making. In relatives of affected patients predictive genetic testing provides the opportunity for an early therapeutic intervention.

Acute heart failure (HF) is a major public health concern, responsible for >26 million hospitalizations per year worldwide. Many trials have investigated new therapeutic options for acute HF, with most revealing equivocal results. Successful innovations in therapy for acute HF have remained limited, and standard of care has remained largely unchanged over the past decade, suggesting the need for a new approach for therapeutic decision making and clinical trial design in acute HF. This manuscript focuses on one approach that could prove useful in the development and application of novel therapies: classification of patients based on clinical profiles. While previous attempts at developing clinical profiles were successful in stratifying patients based on clinical and laboratory variables, they have not been utilized for personalized treatment strategies that improve patient outcomes. We suggest a new approach to the creation of clinical profiles that could stratify patients based on their underlying aetiology and their response to novel interventions. We also investigate novel analytic approaches to the creation of new clinical profiles that both investigators and clinicians alike could utilize to inform clinical trial design and the application of new therapies. Despite a large number of clinical trials for new therapeutic options, the treatment of acute HF has seen few advances over the past decades. Innovative approaches to patient selection through the use of clinical profiles could help to identify patients most likely to benefit from novel interventions and lead to the discovery of new therapeutic options.

Background: The treat-to-target (T2T) strategy has become established in several medical specialties as a key guidance to optimal therapeutic decision making. T2T may be effective in the assessment of the biologic class of agents called interleukin (IL)-17 inhibitors, which are emerging as a safe and effective treatment option for autoimmune inflammatory conditions such as plaque psoriasis, psoriatic arthritis (PsA), and ankylosing spondylitis (AS). Objective: The objective of this article is to use a T2T approach for the evaluation of the effectiveness and safety of IL-17 inhibitors in the management of patients with plaque psoriasis, PsA, and AS. Methods: Following a comprehensive literature search, a full-day meeting was convened to discuss and identify the T2T targets for psoriasis, PsA, and AS. Clinical trial evidence was presented for the approved IL-17 inhibitors—secukinumab, ixekizumab, and brodalumab—to assess whether these data meet T2T safety and efficacy targets. Results: All 3 approved agents were significantly superior to placebo and active controls in the achievement of T2T targets for psoriasis. Secukinumab and ixekizumab were likewise associated with significantly better outcomes than controls in the PsA targets, and secukinumab resulted in significant AS target improvements vs placebo. The IL-17 inhibitors were also associated with low rates of serious adverse events and exacerbations of common comorbid conditions. Conclusion: Phase III trial results support the T2T benefit and safety of IL-17 inhibitors according to their specific indications for the management of patients with plaque psoriasis, PsA, and AS.