Clinical Rule Research Articles

DIAGNOSTIC ACCURACY OF D-DIMER ASSAY IN PULMONARY EMBOLISM USING CTPA AS GOLD STANDARD

Objective: To determine the sensitivity and specificity of D-dimer assay for the diagnosis of PE in resource limited settings using CTPA as a gold standard for comparison.
 Study Design: Cross-sectional study.
 Place and Duration of Study: Department of Radiology, Combined Military Hospital, Peshawar, from Feb 2019 to Jul 2020.
 Methodology: A sample of 114 cases of clinically suspected PE presenting in ED were collected by non-probability sampling as per QUADAS 2 domains. D-dimer and CTPA reporting done by separate teams, compilation of data by third team. Using SPSS 23.0, 2×2 contingency table was used to calculate the sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of D-dimer in diagnosing PE.
 Results: Age range 20-50 years (mean: 40.54 ± 5.02 years). Sixty patients were female (52.3%). D- Dimer levels for the diagnosis of PE: Sensitivity: 92.86%, specificity 89.66%, positive predictive value (PPV): 89.66% and negative predictive value (NPV): 92.86%.
 Conclusion: The D-Dimer levels are significantly sensitive and specific in the diagnosis of PE: however keeping in view the high mortality of PE, diagnostic accuracy may be further improved by using D-Dimer levels in conjunction with pretest clinical probability rules.

Exploring the Clinical Point Selection Rules of Acupuncture and Moxibustion in the Treatment of Infantile Enuresis Based on Data Mining Technology.

In order to explore the clinical point selection rules of acupuncture and moxibustion in the treatment of infantile enuresis based on data mining technology, first, it introduces the principle of data mining technology, the global optimization strategy of information extraction + genetic search. In China Biomedical Literature Database, CNKI, Weipu, Wanfang. Use “enuresis,” “enuresis,” “leathering,” “urinary discharge,” “drowning,” “bedwetting,” “nocturia,” “drowning,” “moxibustion,” “moxibustion,” and “moxibustion” as search terms, take (enuresis + enuresis + urination + urination + addiction + bedwetting), (moxibustion + moxibustion + moxibustion)” as the retrieval style. The analysis of the use of moxibustion, the law of acupoint selection by different moxibustion methods, and the frequency analysis of meridian use show that most of the moxibustion methods are used (62 articles, of which 3 articles use 2 moxibustion methods), including non-suppurative moxibustion, ginger moxibustion, medicinal cake moxibustion, salt moxibustion, mild moxibustion, warm acupuncture moxibustion, bird pecking moxibustion, circling moxibustion, and warm moxibustion; among them, mild moxibustion has the highest frequency of use 24 and non-suppurative moxibustion and salt-separated moxibustion have the lowest frequency of use1; there are 4 non-moxibustion methods, which are medicated thread moxibustion methods. Different moxibustion methods for acupoint selection have their own emphasis. The 63 included literatures included 63 prescriptions for moxibustion, 11 prescriptions for acupoints. Analyzing the frequency of acupoint selection, a total of 18 ear acupoints are involved, and the total frequency of auricular acupoints is 54 times; 44 points are involved (including 1 odd point outside the meridian), the total frequency of acupoints is 300 times, and the total frequency of meridian points is 298, and the total frequency of Jingwaiqi acupoints (Sishencong) is 2. The results can provide great help for the clinical selection of acupuncture points for the treatment of infantile enuresis.

A Comprehensive Review of Celecoxib Oral Solution for the Acute Treatment of Migraine.

A migraine is a clinical diagnosis with a presentation of one or more severe unilateral or bilateral headache(s) often preceded by an aura and typically accompanied by nausea, vomiting, photophobia, and/or phonophobia. This neurological disease is often debilitating and greatly affects the quality of life of those it inflicts. In fact, a recent study conducted by the Global Burden of Disease and published in The Lancet Neurology revealed that migraines ranked second to only back pain as the most disabling disease. Triggers for migraines have ranged from female sex, low socioeconomic status, and diet to loud noises, sleep hygiene, and stress. Along with its clinical presentation, laboratory tests and imaging help rule out other potential causes of the headache and lead to a diagnosis of migraine. Migraines are typically divided into three phases: prodromal, headache, and postdrome. The pathophysiology of each phase remains under investigation, with differing theories regarding their pathways. Existing therapies are abortive therapies for acute migraines or preventative therapies. Abortive therapy consists of NSAIDs and triptans. Preventative therapies include tricyclic antidepressants, calcium channel blockers, beta-blockers, and anticonvulsants. In this review, we focus on the role of NSAIDs and the COX-2 inhibitor, celecoxib oral solution, for the abortive treatment of acute migraines.

From basic to advanced computerised intravenous to oral switch for paracetamol and antibiotics: an interrupted time series analysis

ObjectivesEarly switch from intravenous to oral therapy of bioequivalent drugs has major advantages but remains challenging. At our hospital, a basic clinical rule was designed to automatically alert the physician...

Initial tumour burden and hidden oligometastatic disease in phase 3 clinical trials.

Initial tumour burden is widely acknowledged to be a strong prognostic factor for cancer treatment, and the difference among polymetastatic and oligometastatic cancers in clinical trials is gaining the attention of oncologists. Randomised phase 3 trials represent the gold standard approach in testing new drugs against cancer. Notably, the selection of patients for inclusion in phase 3 trials relies on prespecified clinical and methodological rules (eg, clinical characteristics, randomisation procedure, and stratification factors) to keep the risk of biases affecting the strength and standardisation of results as low as possible.

Clinical data mining reveals Gancao-Banxia as a potential herbal pair against moderate COVID‐19 by dual binding to IL-6/STAT3

BackgroundCoronavirus disease 2019 (COVID-19) keeps spreading globally. Chinese medicine (CM) exerts a critical role for the prevention or therapy of COVID-19 in an integrative and holistic way. However, mining and development of early, efficient, multisite binding CMs that inhibit the cytokine storm are imminent. MethodsThe formulae were extracted retrospectively from clinical records in Hunan Province. Clinical data mining analysis and association rule analysis were employed for mining the high-frequency herbal pairs and groups from formulae. Network pharmacology methods were applied to initially explore the most critical pair's hub targets, active ingredients, and potential mechanisms. The binding power of active ingredients to the hub targets was verified by molecular docking. ResultsEight hundred sixty-two prescriptions were obtained from 320 moderate COVID-19 through the Hunan Provincial Health Commission. Glycyrrhizae Radix et Rhizoma (Gancao) and Pinelliae Rhizoma (Banxia) were used with the highest frequency and support. There were 49 potential genes associated with Gancao-Banxia pair against moderate COVID-19 patients. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) indicated that Gancao-Banxia might act via inflammatory response, viral defense, and immune responses signaling pathways. IL-6 and STAT3 were the two most hub targets in the protein-protein interaction (PPI) network. The binding of five active ingredients originated from Gancao-Banxia to IL-6-STAT3 was verified by molecular docking, namely quercetin, coniferin, licochalcone a, Licoagrocarpin and (3S,6S)-3-(benzyl)-6-(4-hydroxybenzyl)piperazine-2,5-quinone, maximizing therapeutic efficacy. ConclusionsThis work provided some potential candidate Chinese medicine formulas for moderate COVID-19. Among them, Gancao-Banxia was considered the most potential herbal pair. Bioinformatic data demonstrated that Gancao-Banxia pair may achieve dual inhibition of IL-6-STAT3 via directly interacting with IL-6 and STAT3, suppressing the IL-6 amplifier. SARS-CoV-2 models will be needed to validate this possibility in the future.

Self-management program for patients with chronic kidney disease (SMP-CKD) in Southern China: protocol for an ambispective cohort study

BackgroundChronic kidney disease (CKD) is a major global health problem. Short-term self-management has been considered to effect some renal and psychological endpoints. However, there are currently very few studies about self-management for CKD that a) have been scientifically designed by a theory-based framework and b) that evaluate the long-term effects and working mechanism. This study presents the rationale and design of a theory-based cohort study to explore how this self-management intervention works and its effectiveness on the Chinese CKD population.MethodsIn this ambispective intervention cohort study,1,200 patients with CKD stages 1–5 will be recruited from July 2015 to July 2024 in 3 branches of Guangdong Provincial Hospital of Chinese Medicine (GPHCM) in Guangdong province, China. The patients in the self-management cohort will choose to receive an intervention that consists of education, nutrition/diet modification, lifestyle change recommendation, medication review, and psychology support based on Social Cognition Theory (SCT). The patients in the control cohort will do regular follow-ups based on the clinic rules. All the patients will be followed up for 5 years, or until the occurrence of a primary outcome. Detailed clinical, laboratory markers, nutritional status, psychological exposures and outcome questionaries will be collected semiannually in CKD stage 1–2 and trimonthly in stage 3–5 patients. The primary outcome is the occurrence of composite clinical endpoints (doubling of serum creatinine level, ESKD, loss of renal function (≥ 40% decline in GFR from baseline), death, major cardiovascular or cerebrovascular events). The main secondary outcomes include the absolute change and slope of eGFR, absolute changes of urinary protein creatinine ratio, 24-h urine proteinuria, intact parathyroid hormone level, and self-management adherence rate and quality of life from baseline to end of the study. The effectiveness of self-management will be analyzed and the association between longitudinal trajectories of self-management and renal outcomes will be evaluated.DiscussionThis study aims to provide further evidence for the effectiveness of theory-based self-management in CKD patients and to improve the lives of patients with CKD by slowing progression, improving psychological well-being and overall quality of life.Trial registrationChinese Clinical Trial Register (ChiCTR1900024633). 19 July, 2019. http://www.chictr.org.cn/showproj.aspx?proj=38378

Guidelines for Nanopharmaceutical Products for Regulatory Approval

The word 'nano' refers to a Greek prefix that means 'dwarf' or very little,' and represents a thousand millionth of a meter (10-9) in length. Nanoscience and nanotechnology are the study and application of nanoscale range materials. Initially, the term Nanotechnology was used by N. Taniguchi in 1974 at an international conference on industrial production in Tokyo to characterize the super-thin processing of materials with nanometre accuracy and the fabrication of nano-sized systems (Bayda S. et al., 2020). The usage of nanomaterials has enhanced the application of nanomedicine in various therapeutics area with challenges and limitations over the last ten years. Alteration of the physiochemical, biological, mechanical & other properties of the materials made the nanomaterials and it can be utilized in different useful activities such as drug development, drug target. Nanotechnology utilized novel nanomaterials to make useful products. This technology has been used to overcome the limitations & challenges in different drug therapies. (Harea JI et al., 2017). 
 The combination of nanotechnology with pharmaceuticals and biomedicals is termed nano pharmaceutical. Nanopharmaceuticals is a new technology in current practice. As a result, there are no widely agreed nanopharmaceuticals guidelines. The general idea of regulatory requirements for Active Pharmaceutical Ingredients (API), as stated in the CDSCO's New Drugs and Clinical Trial Rules 2019, was mandatory in drug development pathways. These criteria are also in line with the International Council for Harmonization (ICH) recommendations and international standards that other countries using such items follow. New Drugs and Clinical Trials Rules, 2019 should be followed in different drug development. (Harea JI et al., 2017). 
 Globally, there are important guidelines developed by the United States Food & Drugs Administration (USFDA), International Council for Harmonization (ICH), or Organization for Economic Co-operation and Development (OECD). (Harea JI et al., 2017). 
 Current regulatory approaches by US Food & Drug Administration (FDA), established the nanotechnology task force in August 2006. This regulatory approach encourages the development of nanoproducts. FDA has issued the guidelines in 2007 to the industry to address the benefits & risks of Drugs, medical devices, and other nanoproducts. FDA is also working with other U.S. government agencies to focus on the safety & efficacy of nanoproducts and U.S. initiates the National Nanotechnology Initiative (NNI) which is a federal research & development program to coordinate the effort of all government agencies involved in nanotechnology. The main goal of the NNI is to maintain the class of research & development program, encourage inducing the new technologies in the product, developing the supporting infrastructure & tools needed for nanotechnology (Ventola et al., 2012).

Infective endocarditis misdiagnosed as cANCA – associated vasculitis

A previously healthy 37-year-old man was admitted to a nephrology clinic due to the left-sided abdominal pain, petechiae and recurring hematuria. Laboratory tests revealed high levels of C-reactive protein and Antineutrophil Cytoplasmic Antibodies (cANCA). On this basis, vasculitis was suspected and prednisone in high doses was administered. After 30 days of immunosuppressive treatment, due to persistence of symptoms, the patient was referred for an ambulatory echocardiographic study, and because of the abnormal result, he was admitted to our department. On admission, the patient was clinically in good condition. However, the physical examination revealed a systolic-diastolic heart murmur. Transthoracic echocardiography demonstrated a vegetation attached to the non-coronary aortic leaflet and severe aortic insufficiency. Additionally, an abnormal, perforated, bulging of the anterior mitral leaflet was present, with severe mitral insufficiency (Figure 1). Three blood cultures were positive for Streptoccocus sanguinis. Therefore, the patient was diagnosed with IE according to the modified Duke criteria. Subsequently, the treatment was adjusted to include intravenous antibiotic therapy with vancomycin and ceftriaxone. Afterwards, the patient was qualified for the replacement of the aortic and mitral valves with mechanical valve prostheses. The procedure was uneventful and the patient was discharged home in good condition. The medical history of this patients is an outstanding example of how complex and misleading the IE diagnosis can be. A selected laboratory test, like cANCA is indeed an important diagnostic marker for vasculitis [1,2]. However, several infectious diseases have been reported to stimulate positive cANCA tests and therefore to mimic vasculitis. One of them is infective endocarditis, which is known to initiate the immune complex disease in about 25% of patients [3,4]. One could speculate that an immunosuppressive treatment, in our patient might have led to a blunted antibacterial response, and potentially to the expansion of the endocardial infection with the bivalvular involvement, while reducing clinical symptoms. Our patient can be a reminder of the clinical rule, that before the definitive diagnosis and treatment of suspected vasculitis, an active infection, especially IE must be excluded [5].

Promoting β-lactam utilization through suppression of electronic medical record cross-allergy alerts.

Current literature surrounding management of patients with reported β-lactam allergies focuses on allergy delabeling. Standard clinical decision support tools have not been optimized to be compatible with the currently accepted cross-reaction rate of 1% to 2%. This potentially promotes use of non-β-lactam antibiotics, which are often not first-line therapy and may carry increased risks. The impact of electronic medical record (EMR) clinical decision support tool optimization on utilization of β-lactam antibiotics in β-lactam-allergic patients was evaluated. A retrospective pre-post β-lactam cross-allergy EMR alert suppression quality improvement intervention cohort study of β-lactam-allergic adult inpatients prescribed antibiotics was conducted. Preintervention baseline data were collected for an initial cohort admitted during September 2018. The intervention, in which clinical decision support rules were updated to display β-lactam cross-sensitivity allergy alerts only for β-lactam-allergic patients with documentation of organization-defined high-severity reactions of anaphylaxis, hives, and shortness of breath, was implemented August 20, 2019. The postintervention cohort included patients admitted during September 2019. A 91% increase in the percentage of β-lactam-allergic patients who received a β-lactam agent at any time during their admission was noted after the intervention (26.6% vs 51%, P < 0.001). Statistically significant decreases in prescribing of alternative antibiotic classes were seen for fluoroquinolones (decrease from 45.3% to 26%, P < 0.001), aminoglycosides (decrease from 9.4% to 2.9%, P = 0.002), and aztreonam (decrease from 30% to 16.7%, P < 0.001). EMR β-lactam cross-allergy alert optimization consistent with current literature significantly improved the utilization of alternative β-lactam subclasses, mostly through β-lactam prescribing as initial therapy in β-lactam-allergic patients.

Improving appropriate use of anticoagulants in hospitalised patients: A pharmacist-led Check of Medication Appropriateness intervention.

Inappropriate anticoagulant use increases the risk of bleeding and thrombotic events. We implemented clinical decision rules to promote judicious medication use, as part of the 'Check of Medication Appropriateness' (CMA). The CMA is a pharmacist-led review service, targeting potentially inappropriate prescriptions (PIPs). In this analysis, we aimed to evaluate the impact of the CMA on anticoagulant prescribing. The number of anticoagulant-related PIPs was evaluated before and after implementation of the intervention in a quasi-experimental interrupted time series analysis. The pre-implementation cohort received usual care. The anticoagulant-focused CMA, comprising 13 clinical rules pertaining to anticoagulation therapies, was implemented in the post-implementation cohort. Segmented regression analysis was used to assess the impact of the intervention on the number of residual PIPs. A residual PIP was defined as a PIP which persisted up to 48 hours after the CMA intervention. Total number of recommendations and acceptance rate were documented for the 2-year post-implementation period. Pre-implementation, we observed 501 PIPs in 466 inpatients on 36 days, with a median proportion of 78.5% (range: 46.2%-100%) residual PIPs per day. Post-implementation, 538 PIPs were detected in 485 patients over the same number of days. The CMA intervention reduced the median proportion to 18.2% (range: 0-100%) per day. The effect coincided with an immediate relative reduction of 70% (95%CI 0.19-0.46) in anticoagulant-related residual PIPs. Post-implementation, 2778 recommendations were provided and 75.1% were accepted. Our CMA approach significantly reduced anticoagulant-related PIPs. Implementing a pharmacist-led intervention, based on clinical rules, may support safer prescribing of anticoagulants.

Cost-effectiveness of check of medication appropriateness: methodological approach.

Background Adverse drug events following inappropriate prescribing in the hospital cause a substantial and avoidable medical and economic burden to hospitals, payers and patients alike. A clinical rule-based, pharmacist-led medication-review service, the 'Check of Medication Appropriateness' (CMA) was implemented in the University Hospitals Leuven. The CMA is shown to be effective in reducing potentially inappropriate prescriptions. Aim This study investigated whether this centralised clinical pharmacy service is cost-effective. Method We performed a cost-effectiveness analysis of three clinical rules of the CMA, targeting adverse drug events at three levels of severity: A) persistent opioid-induced constipation, B) ketorolac-induced gastrointestinal bleeding and C) drug-induced Torsade de Pointes. A decision tree was developed for each clinical rule. Both intervention costs as well as total costs associated with the occurrence of an adverse drug event were considered. The outcomes were reported in the form of an incremental cost-effectiveness ratio, expressed as an incremental cost per adverse drug event avoided. Results Applying clinical rules to avoid persistent opioid-induced constipation and ketorolac-induced gastrointestinal bleeding were cost-saving. Implementation of a medication check to avoid drug-induced Torsade de Pointes costed €8,846 per Torsade de Pointes avoided. Conclusion Our study provides strong indications that the CMA is worth its investment for clinical rules targeting (very) common adverse drug events, that can be avoided with limited expenses. Further research is required to assess the full CMA. The proposed model may be useful to perform cost-effectiveness analyses of other centralised clinical pharmacy services targeting inappropriate prescribing, at the level of individual adverse drug events.

Control in the Hospital by Extensive Clinical rules for Unplanned hospitalizations in older Patients (CHECkUP); study design of a multicentre randomized study

BackgroundDue to ageing of the population the incidence of multimorbidity and polypharmacy is rising. Polypharmacy is a risk factor for medication-related (re)admission and therefore places a significant burden on the healthcare system. The reported incidence of medication-related (re)admissions varies widely due to the lack of a clear definition. Some medications are known to increase the risk for medication-related admission and are therefore published in the triggerlist of the Dutch guideline for Polypharmacy in older patients. Different interventions to support medication optimization have been studied to reduce medication-related (re)admissions. However, the optimal template of medication optimization is still unknown, which contributes to the large heterogeneity of their effect on hospital readmissions. Therefore, we implemented a clinical decision support system (CDSS) to optimize medication lists and investigate whether continuous use of a CDSS reduces the number of hospital readmissions in older patients, who previously have had an unplanned probably medication-related hospitalization.MethodsThe CHECkUP study is a multicentre randomized study in older (≥60 years) patients with an unplanned hospitalization, polypharmacy (≥5 medications) and using at least two medications from the triggerlist, from Zuyderland Medical Centre and Maastricht University Medical Centre+ in the Netherlands. Patients will be randomized. The intervention consists of continuous (weekly) use of a CDSS, which generates a Medication Optimization Profile, which will be sent to the patient’s general practitioner and pharmacist. The control group will receive standard care. The primary outcome is hospital readmission within 1 year after study inclusion. Secondary outcomes are one-year mortality, number of emergency department visits, nursing home admissions, time to hospital readmissions and we will evaluate the quality of life and socio-economic status.DiscussionThis study is expected to add evidence on the knowledge of medication optimization and whether use of a continuous CDSS ameliorates the risk of adverse outcomes in older patients, already at an increased risk of medication-related (re)admission. To our knowledge, this is the first large study, providing one-year follow-up data and reporting not only on quality of care indicators, but also on quality-of-life.Trial registrationThe trial was registered in the Netherlands Trial Register on October 14, 2018, identifier: NL7449 (NTR7691). https://www.trialregister.nl/trial/7449.

Duality of Interactions Between TGF-β and TNF-α During Tumor Formation.

The tumor microenvironment is essential for the formation and development of tumors. Cytokines in the microenvironment may affect the growth, metastasis and prognosis of tumors, and play different roles in different stages of tumors, of which transforming growth factor β (TGF-β) and tumor necrosis factor α (TNF-α) are critical. The two have synergistic and antagonistic effect on tumor regulation. The inhibition of TGF-β can promote the formation rate of tumor, while TGF-β can promote the malignancy of tumor. TNF-α was initially determined to be a natural immune serum mediator that can induce tumor hemorrhagic necrosis, it has a wide range of biological activities and can be used clinically as a target to immune diseases as well as tumors. However, there are few reports on the interaction between the two in the tumor microenvironment. This paper combs the biological effect of the two in different aspects of different tumors. We summarized the changes and clinical medication rules of the two in different tissue cells, hoping to provide a new idea for the clinical application of the two cytokines.

The Psychiatrist as an Expert Witness.

A psychiatrist, in India, unlike in the western developed world often is required to play dual role of being a treating psychiatrist and that of an expert witness for the same patient. In the clinical scenario, the principle of therapeutic alliance comes into play, while in the court of law, he/she needs to play the role of assisting the judicial system to deliver “justice.” Psychiatrist role in the court is directed by the court rules and not by the clinical rules. This chapter aims to describe the various roles played by the psychiatrist in the court room and provides a basic outline of the medicolegal expectations from a psychiatrist.

Adherence to Best Practice Advice for Diagnosis of Pulmonary Embolism.

This study evaluated clinician adherence to the American College of Physicians Best Practice Advice for diagnosis of pulmonary embolism. A prospective, single-center, descriptive design was utilized. A heterogeneous sample of 111 hemodynamically stable adult inpatients with a computed tomography pulmonary angiogram ordered was consented. Electronic medical records were reviewed for demographic and clinical variables to determine adherence. The 6 individual best practice statements and the overall adherence were evaluated by taking the sum of "yes" answers divided by the sample size. Overall adherence was 0%. Partial adherence was observed with clinician-recorded clinical decisions rules and obtaining d-dimer (3.6% [4/111] and 10.2% [9/88], respectively) of low/intermediate probability scorers. Age adjustment of d-dimer was not recorded. Computed tomography pulmonary angiogram was the first diagnostic test in 89.7% (79/88) in low/intermediate probability patients. In hemodynamically stable, hospitalized adults, adherence to best practice guidelines for diagnosis of pulmonary embolism was minimal. Clinical utility of the guidelines in hospitalized adults needs further evaluation. Systems problems (eg, lack of standardized orders, age-adjusted d-dimer values, information technology support) likely contributed to poor guideline adherence.

Safety and clinical use rules of donor blood and (or) its components

The article is devoted to an urgent problem of public health — transfusion of donor blood and (or) its components. The author examines the issues of the safety of the process of clinical use of blood and (or) its components, complications of transfusion in the light of the regulatory legal acts that came into force on January 01, 2021. The stated information indicates the role of specialists with secondary medical education in the implementation of transfusion.

A Framework for Using Real-World Data and Health Outcomes Modeling to Evaluate Machine Learning–Based Risk Prediction Models

ObjectivesWe propose a framework of health outcomes modeling with dynamic decision making and real-world data (RWD) to evaluate the potential utility of novel risk prediction models in clinical practice. Lung transplant (LTx) referral decisions in cystic fibrosis offer a complex case study. MethodsWe used longitudinal RWD for a cohort of adults (n = 4247) from the Cystic Fibrosis Foundation Patient Registry to compare outcomes of an LTx referral policy based on machine learning (ML) mortality risk predictions to referral based on (1) forced expiratory volume in 1 second (FEV1) alone and (2) heterogenous usual care (UC). We then developed a patient-level simulation model to project number of patients referred for LTx and 5-year survival, accounting for transplant availability, organ allocation policy, and heterogenous treatment effects. ResultsOnly 12% of patients (95% confidence interval 11%-13%) were referred for LTx over 5 years under UC, compared with 19% (18%-20%) under FEV1 and 20% (19%-22%) under ML. Of 309 patients who died before LTx referral under UC, 31% (27%-36%) would have been referred under FEV1 and 40% (35%-45%) would have been referred under ML. Given a fixed supply of organs, differences in referral time did not lead to significant differences in transplants, pretransplant or post-transplant deaths, or overall survival in 5 years. ConclusionsHealth outcomes modeling with RWD may help to identify novel ML risk prediction models with high potential real-world clinical utility and rule out further investment in models that are unlikely to offer meaningful real-world benefits.

Witnessing death does not necessarily relieve the dis-comfort of death: analysis of the relationship between religiosity and thanatophobia in medicine undergraduate students

Introduction: It is known that very few issues related to death and religiosity/spirituality are addressed during medical graduation. Understanding the process of death and dying is still a problem for medical students before the terminal condition of a patient. Probably the medical students of the fifth graders overestimate their abilities, probably because they have not yet had contact with terminally ill patients or because they have not graduated, they do not take responsibility for the death of a patient they are following. In Brazil, many students believe that the topic of spirituality influences health, but they do not feel prepared to address this issue with patients. Objective: It was to analyze whether there is a relationship between religiosity and thanatophobia in medical students. It also analyzed whether there was a correlation between fear of death and specific religions, sex and age, and the index of religiosity with sex and age. Methods: Followed a prospective observational cross-sectional model, following the STROBE clinical research rules. This study was analyzed and approved by the Research Ethics Committee (CEP) according to a substantiated opinion number 2,031,705, and obtaining the patient's consent. Results: A total of 542 students (61.2% of the total) answered the questionnaire. Most were female (65.7%) and with a mean age of 22.31 (ranging from 17 to 39 years). The majority of students have a religion (90.1%) and 90.4% considered it important to address the issue of death and religiousness during graduation. In this study, it was observed that most students, in addition to having some kind of religion, consider it important to address the themes highlighted during the course. This was similar to the findings in other studies. There was no statistically significant relationship between having a religion and being less afraid of death. However, students with higher levels of intrinsic religiosity showed greater discomfort when dealing with terminal patients. Furthermore, no studies comparing these two subjects were found. It was also found in this research that students with high levels of religiosity consider it more important to address the issues in question, with the majority being female students. Conclusion: It is necessary to include the topic in the medical academy, and it is essential to prepare a more humanistic and dedicated professional for patients, whether active or palliative treatment.

Clinical ABCDE rule for early melanoma detection.

The ABCDE rule systematizes warning signs for malignant melanoma (MM). To evaluate whether the ABCDE signs are associated with early detection of MM. Based on a retrospective study over 11.5 years, we assessed whether ABCDE signs are associated with early diagnosis of MM. In total, 144 MM were included; 52 (36.1%) in situ and 92 (63.9%) invasive lesions. For 23.6%, the MM were first suspected by an individual other than a dermatologist. The "E sign" was significantly less frequent among in situ lesions (32.7% versus 50.0%; p = 0.044). Based on adjusted analyses, the probability of MM being first suspected by a non-dermatologist consistently increased with the number of ABCDE signs of the lesion, ranging from 8% for a neoplasm with no ABCDE signs to 32% for a lesion with five signs (OR = 1.6; 95%CI: 1.2-2.2; p = 0.004). A higher number of ABCDE signs were associated with a greater chance of MM being first suspected by a non-dermatologist, but not in situ MM diagnosis. Relying on the ABCDE rule alone might result in missing early MM lesions.