Therapeutic Recommendations For Patients Research Articles

Neoadjuvant and Adjuvant Treatments for Early Stage Resectable NSCLC: Consensus Recommendations From the International Association for the Study of Lung Cancer

Advances in the multidisciplinary care of early stage resectable NSCLC (rNSCLC) are emerging at an unprecedented pace. Numerous phase 3 trials produced results that have transformed patient outcomes for the better, yet these findings also require important modifications to the patient treatment journey trajectory and reorganization of care pathways. Perhaps, most notably, the need for multispecialty collaboration for this patient population has never been greater. These rapid advances have inevitably left us with important gaps in knowledge for which definitive answers will only become available in several years. To this end, the International Association for the Study of Lung Cancer commissioned a diverse multidisciplinary international expert panel to evaluate the current landscape and provide diagnostic, staging, and therapeutic recommendations for patients with rNSCLC, with particular emphasis on patients with American Joint Committee on Cancer-Union for International Cancer Control TNM eighth edition stages II and III disease. Using a team-based approach, we generated 19 recommendations, of which all but one achieved greater than 85% consensus among panel members. A public voting process was initiated, which successfully validated and provided qualitative nuance to our recommendations. Highlights include the following: (1) the critical importance of a multidisciplinary approach to the evaluation of patients with rNSCLC driven by shared clinical decision-making of a multispecialty team of expert providers; (2) biomarker testing for rNSCLC; (3) a preference for neoadjuvant chemoimmunotherapy for stage III rNSCLC; (4) equipoise regarding the optimal management of patients with stage II between upfront surgery followed by adjuvant therapy and neoadjuvant or perioperative strategies; and (5) the robust preference for adjuvant targeted therapy for patients with rNSCLC and sensitizing EGFR and ALK tumor alterations. Our primary goals were to provide practical recommendations sensitive to the global differences in biology and resources for patients with rNSCLC and to provide expert consensus guidance tailored to the individualized patient needs, goals, and preferences in their cancer care journey as these are areas where physicians must make daily clinical decisions in the absence of definitive data. These recommendations will continue to evolve as the treatment landscape for rNSCLC expands and more knowledge is acquired on the best therapeutic approach in specific patient and disease subgroups.

Screening and therapeutic recommendations for patients with alcohol use disorder.

Alcohol use disorder (AUD) is the most prevalent substance use disorder worldwide. Early screening can identify patients at risk for developing AUD, creating opportunities for prevention and early intervention. This article encourages the use of AUD screening tools, explores AUD treatments, and aims to equip clinicians with evidence-based strategies to prevent and manage AUD.

Cancer of unknown primary (CUP) through the lens of precision oncology: a single institution perspective

PurposeFor patients with cancer of unknown primary (CUP), treatment options are limited. Precision oncology, the interplay of comprehensive genomic profiling (CGP) and targeted therapies, aims to offer additional treatment options to patients with advanced and hard-to-treat cancers. We aimed to highlight the use of a molecular tumor board (MTB) in the therapeutic management of CUP patients.MethodsIn this single-center observational study, CUP patients, presented to the MTB of the Comprehensive Cancer Center Munich LMU, a tertiary care center, were analyzed retrospectively. Descriptive statistics were applied to describe relevant findings.ResultsBetween June 2016 and February 2022, 61 patients with unfavorable CUP were presented to the MTB, detected clinically relevant variants in 74% (45/61) of patients, of which 64% (29/45) led to therapeutic recommendation. In four out of 29 patients (14%), the treatment recommendations were implemented, unfortunately without resulting in clinical benefit. Reasons for not following the therapeutic recommendation were mainly caused by the physicians’ choice of another therapy (9/25, 36%), especially in the context of worsening of general condition, lost to follow-up (7/25, 28%) and death (6/25, 24%).ConclusionCGP and subsequent presentation to a molecular tumor board led to a high rate of therapeutic recommendations in patients with CUP. Recommendations were only implemented at a low rate; however, late GCP diagnostic and, respectively, MTB referral were found more frequent for the patients with implemented treatment. This contrast underscores the need for early implementation of CGP into the management of CUP patients.

Gender-dependent compliance with therapeutic recommendations in patients with heart failure

Abstract Funding Acknowledgements Type of funding sources: None. Non-pharmacological therapies are one of the key elements in the treatment of heart failure. Those therapies are effective if the instructions are followed. Aim of this study was the assessment of whether gender influence the degree of compliance with therapeutic recommendations in elderly patients with heart failure. Methods 180 patients (aged 72,77 ± 7,98) with heart failure recognized based on ESC criteria were included in the study. In all, capability for self-care of patients with HF were analyzed by using Polish version the nine-item European Heart Failure Self-care Behavior Scale (EHFScBS-9). The complete results are obtained by adding up the number of points – the more the points, the worse is the capability for self-care. Patients were divided into 2 groups according to the gender: 70,6% men and 29,4% women. Results A satisfactory or good level of the capability for self-care of patients with HF was found in 27,8% of the patients. More than 65% of the patients followed the recommendations for taking medication and 41,7% used a low-sodium diet, while only 5,5% of the patients followed the recommendations for physical exercise. The average value of the level of the capability for self-care of patients was 27,7 ± 5,25 points. Women significantly worse comply with the overall level of self-care (p=00441) and recommendations regarding among the following variables: "I weigh myself every day" (p=0,0342) and "I limit the amount of fluids" (p=0,0139). Exact results of EHFScBS-9 scale are presented in the table below. Conclusion Gender may be a factor in compliance with therapeutic recommendations. Women are less likely to follow therapeutic recommendations for heart failure.

A combined risk model for the multi-encompassing identification of heterogeneities of prognoses, biological pathway variations and immune states for sepsis patients

BackgroundSepsis is a highly heterogeneous syndrome with stratified severity levels and immune states. Even in patients with similar clinical appearances, the underlying signal transduction pathways are significantly different. To identify the heterogeneities of sepsis from multiple angles, we aimed to establish a combined risk model including the molecular risk score for rapid mortality prediction, pathway risk score for the identification of biological pathway variations, and immunity risk score for guidance with immune-modulation therapy.MethodsWe systematically searched and screened the mRNA expression profiles of patients with sepsis in the Gene Expression Omnibus public database. The screened datasets were divided into a training cohort and a validation cohort. In the training cohort, authentic prognostic predictor characteristics (differentially expressed mRNAs, pathway activity variations and immune cells) were screened for model construction through bioinformatics analysis and univariate Cox regression, and a P value less than 0.05 of univariate Cox regression on 28-day mortality was set as the cut-off value. The combined risk model was finally established by the decision tree algorithm. In the validation cohort, the model performance was assessed and validated by C statistics and the area under the receiver operating characteristic curve (AUC). Additionally, the current models were further compared in clinical value with traditional indicators, including procalcitonin (PCT) and interleukin-8 (IL-8).ResultsDatasets from two sepsis cohort studies with a total of 585 consecutive sepsis patients admitted to two intensive care units were downloaded as the training cohort (n = 479) and external validation cohort (n = 106). In the training cohort, 15 molecules, 20 pathways and 4 immune cells were eventually enrolled in model construction. These prognostic factors mainly reflected hypoxia, cellular injury, metabolic disorders and immune dysregulation in sepsis patients. In the validation cohort, the AUCs of the molecular model, pathway model, immune model, and combined model were 0.81, 0.82, 0.62 and 0.873, respectively. The AUCs of the traditional biomarkers (PCT and IL-8) were 0.565 and 0.585, respectively. The survival analysis indicated that patients in the high-risk group identified by models in the current study had a poor prognosis (P < 0.05). The above results indicated that the models in this study are all superior to the traditional biomarkers for the predicting the prognosis of sepsis patients. Furthermore, the current study provides some therapeutic recommendations for patients with high risk scores identified by the three submodels.ConclusionsIn summary, the present study provides opportunities for bedside tests that could quantitatively and rapidly measure heterogeneous prognosis, underlying biological pathway variations and immune dysfunction in sepsis patients. Further therapeutic recommendations for patients with high risk scores could improve the therapeutic system for sepsis.

The Impact of Motor Disability and the Level of Fatigue on Adherence to Therapeutic Recommendations in Patients with Multiple Sclerosis Treated with Immunomodulation.

Aim: The aim of the study was to clarify whether the motor disability and the fatigue-related syndrome affect the level of compliance with therapeutic recommendations.Methods: Prospective studies were conducted among 165 patients treated under the drug program - Treatment of Multiple Sclerosis (MS) at the Department of Neurology and Clinical Neuroimmunology of the Regional Specialist Hospital in Grudziadz (Poland). The research was carried out by the method of diagnostic survey, questionnaire technique with the use of standardized research tools. The Adherence in Chronic Diseases Scale (ACDS) was used to assess the level of compliance with therapeutic recommendations. The Expanded Disability Status Scale (EDSS) was used to assess the degree of disability, and the Modified Fatigue Impact Scale (MFIS) was used to assess the degree of disability. The Chi-square test, Shapiro-Wilk test and Kruskal-Wallis were used.Results: The statistical analysis showed that there is a relationship (p=0.0055) between the patient's motor disability assessed in the EDSS scale and the level of compliance with therapeutic recommendations assessed in the ACDS scale. The higher the patient's disability level (EDSS 4.5-6.5), the lower the treatment adherence rate. The conducted research shows that the average score in the MFIS scale for individual levels of compliance with therapeutic recommendations expressed in the ACDS scale is, respectively: for the low level - 38.3 MFIS points, for the medium level - 34.4 MFIS points and for the high level- 33.2 MFIS points. The obtained results were not statistically significant (p=0.6098).Conclusion: It was found that the level of adherence to therapeutic recommendations in patients with relapsing-remitting multiple sclerosis treated with immunomodulation in the study group remained high. There is a relationship between the patient's disability and the level of adherence to therapeutic recommendations.

Acceptance of Illness and Compliance with Therapeutic Recommendations in Patients with Hypertension.

Arterial hypertension (AH) is one of the most common cardiovascular diseases increasing mortality rates in Poland and worldwide. Due to its prevalence, complications and treatment costs, AH is a significant health-related, economic and social problem. The aim of this study was to assess the level of acceptance of illness and compliance with therapeutic recommendations in patients with AH. The study included 200 outpatient hypertensive patients, 85 men and 115 women aged 49.1 ± 11.6, and used the standardized acceptance of illness (AIS), the eight-item Morisky Medication Adherence Scale (MMAS-8) and author’s design questionnaires. The level of acceptance of illness was found to be as follows: higher in men than in women, unaffected by comorbidities or sociodemographic factors such as residence and professional activity, decreasing with age, and correlating negatively with the duration of antihypertensive therapy. The level of adherence and compliance did not affect the AIS score and increased with the level of education. The study population demonstrated an overall good level of acceptance of illness. Men were characterized by lower levels of adherence and compliance. Patients with AH presented a moderate level of adherence and compliance, which indicates the need for providing active education, support and extensive cooperation facilitating their conformity to therapeutic recommendations.

Adherence to Therapeutic Recommendations in Patients Suffering from Multiple Sclerosis

Introduction. Multiple sclerosis is a chronic, inflammatory, immune demyelinating disease of the central nervous system. The effectiveness of MS treatment depends primarily on the effectiveness of drugs and the patient’s compliance with the principles of therapy.Aim. The main aim of the study was to assess the level of adherence to therapeutic recommendations in patients with multiple sclerosis.Material and Methods. The research was carried out at the Department of Neurology and Clinical Neuroimmunology of the Regional Specialist Hospital in Grudziądz. On average 165 patients suffering from multiple sclerosis were qualified for the study. The study was conducted using the method of diagnostic survey. The variables were measured using the proprietary questionnaire containing sociodemographic and medical data and the standardized adherence scale in chronic diseases (ACDS).Results. The analysis of own research showed that patients with high-level multiple sclerosis adhere to the therapeutic recommendations (p = 0.001). The study group reported the fatigue syndrome at all ACDS levels (p = 0.002). There was no relationship between the occurrence of adverse effects of pharmacotherapy and the level of compliance with therapeutic recommendations (p &gt; 0.05).Conclusions. It was found that the level of adherence to therapeutic recommendations in patients suffering from multiple sclerosis in the study group remained at a high level. (JNNN 2020;9(3):103–107)

The impact of knowledge and effectiveness of educational intervention on readiness for hospital discharge and adherence to therapeutic recommendations in patients with acute coronary syndrome

Introduction: ESC guidelines emphasize the importance of educating patients after acute coronary syndromes aimed at familiarizing the patient with the essence of the disease, the principles of self-control and self-care as well as actions enhancing health maintenance. Aim: The aim of the study was to assess the impact of knowledge and effectiveness of educational intervention on readiness for discharge from the hospital and compliance with therapeutic recommendations six months after discharge. Material and methods: The study group consisted of 218 patients (28.9% women and 71.1% men) aged 31 to 90 years (63.0 ± 11.24) treated with coronary angioplasty for myocardial infarction. The effectiveness of educational intervention was assessed by comparing patients’ knowledge on the day of admission (1KE) and discharge from the hospital (2KE). Knowledge was assessed in 3 aspects: knowledge of symptoms, knowledge of the disease, and knowledge of prevention. Education was provided between 1KE and 2KE based on the brochure entitled “Myocardial Infarction”. The level of knowledge on the day of discharge and the increase in knowledge obtained after education (ΔKE) were referred to the level of Readiness for Hospital Discharge after Myocardial Infarction Scale (RHD-MIS) and to the level of adherence in chronic diseases scale (ACDS). Results: As a result of the education carried out between 1KE and 2KE, a significant increase in knowledge was obtained (p < 0.05). There was no correlation between ΔKE and RHD-MIS. However, it was shown that a higher level of knowledge at discharge (2KE) was associated with a higher RHD-MIS result (R = 0.17; p = 0.01). The highest impact on the RHD-MIS result was due to the level of knowledge of disease symptoms in 2KE: 75.5 ± 19.5%, 76.4 ± 21.1%, 85.8 ± 16.4% for low, medium and high RHD-MIS results (p = 0.002) ; R = 0.15; p = 0.0003. Knowledge of the disease symptoms in 2KE was associated with the patient’s expectations in RHD-MIS - a higher level of knowledge was associated with higher patient expectations, respectively: 73.2 ± 21.7%, 80.0 ± 18.5%, 82.9 ± 19.2 for low, medium and high RHDMIS (p = 0.02); R = 0.19; p = 0.006. There was no correlation between ΔKE or 2KE and ACDS results 6 months after discharge. Conclusions: The educational brochure is an effective tool in improving patients’ level of knowledge. Better knowledge of the symptoms of coronary artery disease and myocardial infarction is associated with a higher degree of readiness for discharge from the hospital but does not affect the observance of therapeutic recommendations in the field of pharmacotherapy after 6 months.

Assesment of TDApp1 an eHelath Tool to Make Therapeutic Recommendations for Patients With ADHD

Assesment of TDApp1 an eHelath Tool to Make Therapeutic Recommendations for Patients With ADHD

Combined Retro- and Prospective Analysis of Adherence to Guidelines and Patient-Tailored Therapeutic Recommendations in Patients with Myelodysplastic Syndromes (MDS) at a Tertiary Care Centre

Introduction The effect of adherence to treatment guidelines has not yet been evaluated in myelodysplastic syndromes (MDS). Based on the large Düsseldorf MDS Registry, we explored adherence to European LeukemiaNet (ELN) guidelines as well as MDS expert recommendations in clinical routine. Methods In a preliminary retrospective analysis of 1658 patients documented in the Düsseldorf MDS registry, we reviewed if treatment was in accordance with the published ELN guidelines from 2014. The following treatments were considered: erythropoiesis stimulating agents (ESA), iron chelation, Lenalidomide, hypomethylating agents (HMA), intensive chemotherapy, and allogeneic stem cell transplantation (alloSCT). Since patients were diagnosed between 1982 and 2018, clinical decision-making could not be exclusively based on current guidelines. Therefore, we also performed a prospective analysis of 381 patients who received patient-tailored treatment recommendations, considering, IPSS-R, MDS-CI, HCT-CI, distance to our center, and ELN guidelines, with special attention to the above-mentioned treatment options. In addition, we conducted a matched-pair analysis, comparing patients who received a certain treatment with patients who, though eligible, did not receive it. Information regarding adherence to treatment recommendations was obtained by searching medical files and contacting primary care physicians. Probability of survival was estimated using the Kaplan-Meier method. Results The retrospective cohort was followed for a median of 22 months (1-500 months). Patients treated in accordance with the ELN guideline did not gain a significant survival benefit in the subgroups treated with ESA, iron chelation, Lenalidomide, HMA, and intensive chemotherapy, compared to patients who were eligible for the respective treatment but did not receive it. Solely the group of patients undergoing alloSCT derived a significant survival benefit compared to patients not receiving alloSCT despite qualifying for this treatment according to ELN criteria (30 vs 18 months, p=0.011, 95% CI 16.86; 25.14, fig. 1). The prospective cohort was followed for a median of 14 months (1-195 months). A median of four months elapsed before treatment was started. Non-adherence to patient-tailored therapeutic recommendations was found in 33% of the patients. The proportion of non-adherence was higher for intensive chemotherapy (47%) and lowest for patients receiving supportive treatment (13%) like ESA and chelation therapy. In the prospective group, the matched-pair study showed again that patients receiving ESA, iron chelation, Lenalidomide, HMA or intensive chemotherapy did not gain a significant survival benefit from adherence to the respective treatment recommendations. Again, survival only differed between patients adhering to and patients not adhering to a recommendation for alloSCT (median survival of 74 vs 28 months; 95% CI 7.5; 48.5, p=0.015). Conclusions According to current ELN guidelines, 33% of patients did not receive the treatment they were eligible for. Non-adherence to patient-tailored treatment recommendations from our tertiary referral center was found in 33% of the patients. Based on our two patient cohorts, supportive care regimens, Lenalidomide, HMA, as well as intensive chemotherapy do not appear to improve overall survival, whereas allogeneic stem cell transplantation provided a significant survival benefit in both groups. In summary, while adherence to MDS treatment guidelines and expert recommendations may influence survival in some of the patients, the overall effect appears to be limited, owing to the limited efficacy of the available treatment options, with the notable exception of alloSCT. However, we cannot exclude that adherence to treatment recommendations has an effect on other relevant outcomes such as quality of life or frequency of hospitalisations due to infections, bleeding and cardiovascular events. Finally, a systematic and standardized assessment of guideline-adherence, reasons for non-adherence, and impact on relevant outcomes would be desirable because it would support us in monitoring the quality of care of MDS patients and would allow comparisons to be made between different health economic environments. Disclosures Nachtkamp: Jazz Pharmaceuticals: Honoraria; Celgene: Other: Travel Support. Schroeder:Celgene Corporation: Consultancy, Honoraria, Research Funding. Kobbe:Amgen: Honoraria, Other: Travel support, Research Funding; Neovii: Honoraria, Other: Travel support; Abbvie: Honoraria, Other: Travel support; Roche: Honoraria, Other: Travel support; Biotest: Honoraria, Other: Travel support; Celgene: Honoraria, Other: Travel support, Research Funding; Pfizer: Honoraria, Other: Travel support; Jazz: Honoraria, Other: Travel support; Takeda: Honoraria, Other: Travel support; Medac: Honoraria, Other: Travel support; MSD: Honoraria, Other: Travel support; Novartis: Honoraria, Other: Travel support. Kündgen:Otsuka: Honoraria; Takeda: Honoraria, Other: Travel Support; Novartis: Honoraria. Kaivers:Jazz Pharmaceuticals: Other: Travel Support. Rautenberg:Jazz Pharmaceuticals: Other: Travel Support; Celgene: Honoraria, Other: Travel Support. Gattermann:Novartis: Honoraria; Alexion: Research Funding; Takeda: Research Funding. Bonadies:Novartis: Other: financial support for travel, Research Funding; Roche: Other: financial support for travel, Research Funding; Amgen: Other: financial support for travel; Celgene: Other: financial support for travel, Research Funding; Sanofi Genzyme: Other: financial support for travel; Janssen: Other: financial support for travel. Germing:Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Jazz Pharmaceuticals: Honoraria; Amgen: Honoraria.

Antiplatelet Treatment for Catheter-Based Interventions in High-Risk Patients: Current Guidelines and Expert Opinion.

Catheter-based interventions have revolutionized treatment of both coronary artery disease and aortic valve disease. Yet, these procedures are accompanied by thromboembolic and bleeding complications. Antiplatelet agents and anticoagulants with tolerable risk of bleeding complications are required to protect from recurrent thromboembolic events. Although guidelines for antithrombotic treatment in patients undergoing percutaneous coronary intervention (PCI) and transcatheter aortic valve replacement (TAVR) are available, scarce evidence exists regarding therapeutic recommendations for patients at high risk for thromboembolic events or major bleeding. The choice of optimal antiplatelet therapy after PCI in patients with complex coronary artery disease and concomitant atrial fibrillation often poses a clinical challenge. The antiplatelet therapy in patients undergoing TAVR is so far based mostly on expert consensus. The present review addresses state-of-the-art antithrombotic therapy, particularly focusing on patients at high risk of thromboembolic and bleeding events, and aims to provide recommendations for clinical practice.

European myeloma network recommendations on diagnosis and management of patients with rare plasma cell dyscrasias.

The introduction of novel agents in the management of multiple myeloma and related plasma cell dyscrasias has changed our treatment approaches and subsequently the outcome of patients. Due to current advances, the European Myeloma Network updated the diagnostic and therapeutic recommendations for patients with Waldenström's macroglobulinemia (WM), AL-amyloidosis, monoclonal immunoglobulin deposition disease (MIDD), POEMS syndrome, and primary plasma cell leukemia. For patients with WM, the combination of rituximab with chemotherapy remains the treatment cornerstone, while the Bruton-tyrosine kinase inhibitor ibrutinib has been introduced and approved for relapsed/refractory disease. The management of light chain amyloidosis depends on the presence and severity of heart disfunction. If present, intensification with an autologous stem cell transplantation (ASCT) is not recommended. Further aggregation of misfolded light chains could be prevented by doxycycline or monoclonal antibodies targeting amyloid deposits. Initial treatment generally consists of melphalan/dexamethasone or bortezomib-based regimens. For relapsing patients, one can consider proteasome inhibitors, immunomodulatory agents, melphalan or daratumumab. Because intact or light-chain immunoglobulins are also the culprits for MIDD, the small monoclonal plasma cells' clones should be treated and generally respond well to bortezomib-based treatment. POEMS syndrome is a well-defined clinical entity that can present as solitary bone lesions or disseminated disease. Radiation therapy is used for patients with localized disease and result in long-lasting response. Systemic treatment should be proposed to patients with disseminated disease, but regimens that can worsen a pre-existing polyneuropathy should be avoided. PPCL is located at the other end of the spectrum of plasma cell disorders and is associated with an aggressive disease course and poor prognosis. It requires an imminent, multi-phase and novel agents-based therapy, including induction, ASCT, consolidation and maintenance, with short treatment-free intervals. Patients not eligible for transplant procedures require personalized, intensive therapeutic approach. Allogeneic stem cell transplantation can be used in selected patients.

Application of 21-gene recurrence score results and ASTRO suitability criteria in breast cancer patients treated with intraoperative radiation therapy (IORT)

BackgroundAmerican Society for Radiation Oncology (ASTRO) suitability criteria for accelerated partial breast irradiation (APBI) and the 21-gene recurrence score (RS) were evaluated for prognostic and predictive benefit in IORT patients. MethodsOutcomes of 184 patients completing IRB approved IORT protocol were retrospectively reviewed. Data included demographics, histopathology, RS, adjuvant therapy, locoregional (LRR) and distant recurrences (DR), and breast cancer-specific survival. ResultsThere were 10 (5.4%) breast cancer recurrences, including one breast cancer-specific death. All 184 patients were classified by ASTRO suitability criteria (suitable: 64% (5 LRR), cautionary: 30% (3 LRR), unsuitable: 6.0% (1 LRR, 1 DR leading to death). RS were available in 114 estrogen receptor positive patients (<11: 22% (1 LRR), 11–25: 63% (1 LRR), 26–30: 9%, >30: 6%). Mean follow-up was 55 months. ConclusionsASTRO suitability criteria for APBI and RS were useful in making prognostic and therapeutic recommendations for patients considering IORT.

Abstract 013: A Model for Stroke Prediction Using Claims Data in a Contemporary Cohort of Patients With Atrial Fibrillation Receiving Oral Anticoagulation

Background: Oral anticoagulants (OACs) are recommended for AF patients for the prevention of thromboembolic events, including stroke. Stroke risk stratification scores (e.g., CHA 2 DS 2 -VASc) are used to tailor therapeutic recommendations for patients in different risk groups. However, these were derived before the advent of direct OACs. At present, there is no tool that estimates a patient’s stroke risk, given their individual characteristics, by type of OAC. Methods: We used healthcare utilization data from two independent US databases (MarketScan and Optum) to construct and validate a predictive model of ischemic stroke in patients with AF initiating OACs. Patients with non-valvular AF initiating OACs were identified from the MarketScan data for years 2007-2015. Using bootstrapping methods and backward selection of 44 candidate variables, we developed a model which selected variables predicting stroke. The final model was validated in patients with non-valvular AF in the Optum Clinformatics database in the period 2009-2015. Results: Among 135,523 patients with AF initiating OAC in the MarketScan dataset, 2,028 experienced an ischemic stroke after anticoagulant initiation. The stepwise model identified 15 variables (including type of OAC) associated with ischemic stroke (Table). The discrimination (c-statistic) of the model was adequate [0.68, 95% confidence interval (CI) 0.66-0.70], showing excellent calibration (χ 2 = 7.7 p=0.57). The model was then applied to the 84,549 AF patients in the Optum data set (1408 stroke events). The model showed similar discrimination (c-statistic 0.67, 95%CI 0.65-0.70) and calibration (χ 2 = 12.8 p=0.17). However, previously-developed predicted models had similar discriminative ability (CHA 2 DS 2 -VASc 0.67, 95%CI 0.65-0.68; ATRIA 0.67, 95%CI 0.65-0.68) Conclusion: A novel model using extensive administrative healthcare data for the identification of patients at higher risk of ischemic stroke by type of anticoagulant did not perform better than established simple models.

KDIGO CKD–MBD guideline update: evolution in the face of uncertainty

Management of mineral and bone disorders in patients with chronic kidney disease (CKD–MBD) requires an understanding of the complex interactions among ions, hormones and their target organs. Since publication of the KDIGO CKD–MBD guideline in 2009, our understanding of disease pathophysiology has improved; however, a paucity of high-quality clinical evidence to support specific interventions remains. Using available data, KDIGO has now updated diagnostic and therapeutic recommendations for patients with CKD–MBD.

Diagnostic and therapeutic recommendations for patients with nocturia.

IntroductionNocturia is defined as the urge to urinate at night when the micturition was directly preceded and followed by sleep. Due to its negative impact on the quality of life of patients, an effective treatment for this disease has become a significant therapeutic challenge. The aim of this article was to explain the main risk factors for the occurrence of nocturia and to present diagnostic and therapeutic schemes in the case of nocturnal polyuria (idiopathic night time polyuria).Material and methodsA review of the literature was carried out and the available guidelines of international science societies, which provided the basis for the above recommendations, were analyzed.ResultsDetailed medical history should include information concerning: lower urinary tract symptoms (including nocturia), underlying illnesses, urogenital disorders, previous surgeries and medications administered. Keeping a bladder diary is recommended. The physical examination, depending on the patient's gender, should include gynecological examination with pelvic organ prolapse assessment or prostate evaluation. In laboratory tests, a urinalysis may be used, in particular cases a cytological analysis of urine sediment may be carried out. In addition, a possible ultrasound and/or cystoscopy may be conducted. Nocturia therapy should begin with modifying dietary habits, including compliance with the fluid regimen, avoiding alcohol, coffee and tea. Moderate physical exercise is also recommended. The pharmacological treatment of nocturia caused by nocturnal polyuria is based on the use of desmopressin at a daily single dose of 25 µg for women and 50 µg for men. The use of desmopressin allows for the reduction in the number of nocturia episodes, as well as improves the overall quality of life and sleep. Treatment with desmopressin can also be considered as a form of therapy added in people with an overactive bladder or benign prostatic hyperplasia, in which nocturia is a significant clinical problem.ConclusionsDesmopressin is an effective and safe first-line treatment option in pharmacological therapy of nocturia caused by nocturnal polyuria.

Manejo endodóntico en pacientes con riesgo de osteonecrosis asociada a bifosfonatos. Scoping review

The aim of this article is to review the available evidence on the occurrence of bisphosphonate associated osteonecrosis of the jaw, and endodontic treatment aproaches. An extensive literature search was performed in databases such as, MEDLINE, EMBASE and CENTRAL. Selection criteria to consider endodontics and bisphosphonate-associated osteonecrosis of the jaw were previously defined. Relevant evidence of the articles that met the selection criteria was extracted. The clinical aspects discussed in this article were endodontic indications and therapeutic recommendations in patients with risk of bisphosphonate associated osteonecrosis. Finally, some recommendations are proposed to prevent bisphosphonate associated osteonecrosis of the jaw in the endodontic context

The HDL paradox: what does it mean and how to manage low serum HDL cholesterol level?

The topic of this article is an important practical lipidologic issue, along with familial hypercholesterolaemia and severe hypertriglyceridaemia which have also been recently reviewed in the Polish literature. In this paper, we attempted to summarise current scientific evidence and views on the complex role of HDL in atherogenesis, as well as therapeutic recommendations in patients with low HDL-C level. In summary, it should be noted that the available evidence does not indicate that HDL are not antiatherogenic lipoproteins but rather directs our attention towards their functionality and dysfunctionality accompanying numerous pathologic conditions associated with inflammation. It may be hoped that effective methods to increase the number of functional HDL in the plasma will be developed in future studies, translating to a reduction in CV events and thus deserving a place in clinical practice guidelines.

Timing and outcomes for radical cystectomy in nonmuscle invasive bladder cancer

To provide an overview on the available clinical and pathological factors in high-risk nonmuscle invasive bladder cancer (NMIBC) patients that help to approximate the risk of progression to muscle invasion and identify 'the' patients requiring timely cystectomy. The value of a high-quality transurethral tumor resection is pointed out. Outcomes following radical cystectomy are compared with a primarily bladder preserving strategy. Carcinoma in situ within the prostatic urethra of NMIBC patients impacts on patient's outcome. Therefore, biopsies taken from the prostatic urethra improve the initial tumor staging accuracy. Lamina propria substaging may provide more detailed prognostic information. Lympho-vascular invasion within the transurethral resection specimen may help to detect patients who benefit from timely cystectomy. Recent findings from patients undergoing radical cystectomy including super-extended lymphadenectomy for clinically NMIBC confirm the substantial rate (25%) of tumor understaging. The fact that almost 10% were found to harbor lymph node metastases underlines the necessity to perform a meticulous lymphadenectomy in NMIBC patients undergoing radical cystectomy. High-quality transurethral bladder tumor resection including underlying muscle fibers is of utmost importance. Nevertheless, tumor understaging remains an issue of concern and warrants the value of a second transurethral resection in high-risk NMIBC patients. There is a persisting lack of rigid therapeutic recommendations in patients with high-risk NMIBC. Instead, treatment strategy is based on individual risk factors. However, irrespective of initial treatment strategy, there is a subgroup of high-risk NMIBC patients with progressive disease, leading almost inevitably to death.