Need For Treatment Of Patients Research Articles

Disease burden, clinical management and unmet treatment need of patients with moderate to severe atopic dermatitis; consensus statements, insights and practices from CERTADE (Central/Eastern EU, Russia, Turkiye AD Experts) Delphi panel.

There is limited insight into the current disease burden and everyday clinical management of moderate-to- severe AD in Poland, Czechia, Russia, and Turkiye. Therefore, this study aimed to get information-driven insights regarding the current disease burden and clinical management of patients with moderate-to-severe AD with common and differentiating aspects of the patient journey and establish a consensus. In this modified 2-round Delphi panel, 133 questions were asked in total to 27 dermatologists. A consensus was achieved when 70% of the panel members strongly agreed or agreed (or strongly disagreed or disagreed) with an item. Statements with <40% agreement dropped from the Delphi rounds and were not repeated. The results state that AD has a significant impact on the quality of life for both patients and their families with social and economic consequences in these countries. While there were significant dissimilarities regarding the current treatment approach by preference order and treatment duration among participants, there was also a high percentage of consensus on literature and guideline-based statements. Current topical therapies and the immune response modifiers were not found to be sufficient by panelists to cover the therapeutic needs of patients with moderate-to-severe AD. Moreover, panelists highlighted the significant burden of adverse events with the off-label use of currently available immunosuppressants. These results underlined that there is a significant disease burden with an unmet treatment need for patients with moderate-to-severe AD in Poland, Czechia, Russia, and Turkiye.

Disease burden, clinical management and unmet treatment need of patients with moderate to severe alopecia areata; consensus statements, insights, and practices from CERTAAE (Central/Eastern EU, Russia, Türkiye AA experts) Delphi panel.

This study aims to update the understanding of Alopecia Areata (AA) in Poland, Czechia, Russia, and Türkiye, focusing on the disease burden, clinical management, and patient journey. It seeks to establish a consensus on optimal management strategies for AA in these regions. A modified 2-round Delphi panel was conveyed with 23 Dermatologists (Russia; 4, Türkiye; 7, Poland; 6, and Czechia; 6). The Delphi questionnaire consisted of 61 statements and 43 questions designed to obtain an overall understanding of the perception and acceptance of available information regarding the care of patients with alopecia areata. The study revealed that moderate-to-severe AA significantly impacts patients' and their families' QoL, consistent with previous studies. AA was found to cause more substantial impairment when additional lesions appeared in visible areas besides the scalp. Work and productivity impairment were notably higher in adults with moderate-to-severe AA. Diagnostic consensus highlighted the importance of skin biopsies and trichoscopy, while the need for more practical severity scoring systems was emphasized. Current treatments, including topical therapies, corticosteroids, and systemic immune modifiers, were deemed insufficient, highlighting the unmet medical need. The Delphi study underscores a significant disease burden and unmet medical needs in patients with moderate-to-severe AA. It highlights the necessity of access to novel treatments and further research to develop more effective therapies with a tolerable safety profile. The findings align with global research, emphasizing the psychosocial impact of AA and the need for standardized, effective treatment protocols.

From the history of development of departments of medical service for head and neck tumors

The article presents the history of development of otorhinolaryngology, a medical service associated with the head and neck tumors, as well as head and neck medical departments. The need for treatment of patients with malignant neoplasms in specialized oncological institutions is shown. Analysis of literature data, doctors’ speeches at various scientific conferences and personal contact with specialists in the head and neck cancers from Russia and countries – former republics of the USSR confirms the need for existence of the head and neck tumor departments.

Finerenone: From the Mechanism of Action to Clinical Use in Kidney Disease.

Diabetic kidney disease is a frequent microvascular complication of diabetes and is currently the leading cause of chronic kidney disease and end-stage kidney disease worldwide. Although the prevalence of other complications of diabetes is falling, the number of diabetic patients with end-stage kidney disease in need of kidney replacement therapy is rising. In addition, these patients have extremely high cardiovascular risk. It is more than evident that there is a high unmet treatment need in patients with diabetic kidney disease. Finerenone is a novel nonsteroidal mineralocorticoid receptor antagonist used for treating diabetic kidney disease. It has predominant anti-fibrotic and anti-inflammatory effects and exhibits several renal and cardiac protective effects. This review article summarizes the current knowledge and future prospects of finerenone in treating patients with kidney disease.

Abstract 142: HDAC3 is required for pathognomonic features of Langerhans cell histiocytes

Abstract Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm that develops due to dysregulated dendritic cell (DC) development and most commonly affects the children with an incidence of 2.6 to 8.9 cases per million individuals per year. BRAFV600E, the most common disease-driving mutation, activates the mitogen-activated protein kinase (MAPK) pathway causing pathognomonic features that lead to the accumulation of LCH cells and formation of granulomatous lesions. These features include enhanced myelopoiesis, reduced tissue-egress and acquisition of an oncogene induced senescence-associated secretory phenotype (SASP) (marked by increased expression of anti-apoptotic proteins and inflammatory cytokines). Accumulation of LCH cells can occur in any organ causing a wide range of clinical sequelae, which is directly related to the originating cell bearing the oncogenic mutation. Frontline therapy for LCH involves combination chemotherapy and steroidal anti-inflammatories, or MAPK inhibitors, which have significant toxicity and fail to eliminate disease causing precursors. We have found that HDAC3 is required for epidermal LC homeostasis and hypothesized that LCH cells rely on similar epigenetic factors to LCs. CD11cCre LSL-BRAFV600E (BRAFV600ECD11c) mice develop severe multifocal LCH with pronounced lesion development in their livers and lungs, hepatosplenomegaly, and a reduced lifespan due to the accumulation of LCH cells. To test our hypothesis, we generated BRAFV600ECD11c HDAC3fl/fl (BRAFV600EHD3KO) mice, which produce LCH cells that harbor a conditional deletion in the deacetylase domain of HDAC3. Compared to BRAFV600ECD11c mice, BRAFV600EHD3KO mice exhibited significantly less hepatosplenomegaly, reduced lesional burden, and improved survival indicating reduced LCH disease burden. Compared to BRAFV600ECD11c, flow cytometry showed BRAFV600EHD3KO had reduced numbers of LCH cells in lungs and livers, which were more apoptotic. We also found decreased frequencies of circulating LCH cells and LCH precursors, indicating that a lack of HDAC3 activity prevents the development of LCH cells. Bone-marrow derived LCH-like cells provide a valuable drug screening tool. We treated Bone-marrow derived LCH-like cells with RGFP966, an HDAC3-specific inhibitor, increased apoptosis indicated by annexin-V and DAPI staining, reduced expression of Bcl-2, increased CCR7 expression, and decreased S6 phosphorylation (an indication of a loss of the SASP), thus inhibition of HDAC3 may prove therapeutically efficacious by abrogating pathognomonic features of LCH cells. Together, our findings identify HDAC3 as a critical epigenetic regulator LCH cell pathophysiology and HDAC3 blockade would address a great need in treatment of patients with LCH. Furthermore, our results indicate that LCH cells rely on similar epigenetic regulators as epidermal LCs despite coming from a different myeloid lineage. Citation Format: Peter Dimitrion, Jugmohit Toor, James Ge, Qiyan Wang, Carl Allen, Li Zhou, Qing-Sheng Mi. HDAC3 is required for pathognomonic features of Langerhans cell histiocytes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 142.

Accuracy of Kampala Trauma Score as a Predictor in Assessing the Prognostic Value of Multiple Trauma

Determining a trauma scoring system appropriate for certain conditions will help in predicting mortality and morbidity, and can determine the need for treatment in patients. Kampala Trauma Score (KTS) is a trauma scoring system that uses a decent number of assessment variables and can be used in all general groups. This study was a retrospective prognostic test conducted in Dr. Hasan Sadikin Hospital Bandung, Indonesia, from December 2021 to July 2022. Data obtained was processed using Microsoft Excel and SPSS spreadsheets. The respondents were 66 people with multiple trauma. Results showed that this study was dominated by patients with blunt trauma (n=63, 95.45%). The mean KTS score in this study was 13.08±1.03. In 49 (74.24%) patients who survived, the mean KTS score was 13.41±0.89 and in 17 (25.76%) patients who died, the mean KTS score was 12.12±0.79. The greatest mortality accuracy was at the cutoff point of the KTS score &gt;12 (81.82% accuracy; 70.59% sensitivity; 85.71% specificity). The accuracy value of the KTS score is in line with the ROC where the optimal KTS score is &gt;12 (85.77%). In conclusion, the Kampala trauma score can be used as a predictor in assessing the prognostic value of multiple trauma patients with the obtained cut-point value as it has high accuracy, sensitivity, and specificity values.

Implementation study to introduce clinical guidelines on lipid metabolism disorders into routine practice: results of the first stage

Despite widespread knowledge in the management of patients with lipid metabolism disorders, their application in clinical practice is insufficient. Identification of barriers to the implementation of key principles of clinical guidelines in routine practice is the first step of the implementation study.Aim. To assess the organization and quality of care for patients with dyslipidemia in order to identify barriers to the implementation of the main principles of clinical guidelines in practice.Material and methods. An implementation study was planned, the initial stage of which was to conduct an anonymous online questionnaire among health care representatives of various levels in all Russian subjects.Results. The study involved 788 physicians, 124 heads of medical organizations and 48 chief freelance specialists from 84 Russian subjects. A wide range of barriers was identified: low availability of lipoprotein (a) testing (66,6% of physicians), coronary calcium index (79,4% of physicians, 71,8% of heads of a medical organizations, 79,2% of chief freelance specialists) and CT angiography (70,0% of physicians, 71,0% of heads of a medical organizations, 85,4% of chief freelance specialists). Lack of funds to manage lipid service (55,6% of heads of a medical organizations, 35,4% of chief freelance specialists). The key barrier to regular lipid-lowering therapy and achieving target low-density lipoprotein cholesterol (LDL-C) levels is lack of perceived need for treatment in patients (58,1% of physicians, 80,0% of heads of a medical organizations, 87,5% of chief freelance specialists), for PCSK9-targeted therapy — high cost (44,1% of physicians, 34,7% of heads of a medical organizations, 23,0% of chief freelance specialists). The possible fixed-dose combination therapy for dyslipidemia was positively perceived (59,7% of physicians, 42,0% of heads of a medical organizations, 35,4% of chief freelance specialists). Inclusion of innovative therapy in medicine assistance program will improve the situation in achieving target LDL-C levels (85,6% of physicians, 91,1% of heads of a medical organizations, 95,8% of chief freelance specialists).Conclusion. A wide range of barriers to the implementation of clinical guidelines on lipid metabolism disorders into practice have been identified. Based on the results obtained, the second stage of the implementation study will identify strategies aimed at eliminating the identified barriers.

HDAC3 Is Required for Pathognomonic Features of Langerhans Cell Histiocytes

Langerhans cell histiocytosis (LCH) is a pediatric inflammatory myeloid neoplasm that develops due to dysregulated myeloid cell development. BRAFV600E is the most common disease-causing mutation and constitutively activates the mitogen-activated protein kinase (MAPK) pathway in myeloid lineage precursors leading to the key pathognomonic features of LCH cells. Enhanced myelopoiesis and reduced CCR7 expression promote accumulation of LCH cells in tissues by simultaneously increasing the production of pathological DCs and preventing tissue egress. Furthermore, LCH cells acquire an oncogene induced senescence-associated secretory phenotype (SASP) that depends on mammalian target of rapamycin (mTOR), which is hallmarked by increased expression of anti-apoptotic proteins, inflammatory cytokines, and matrix metalloproteinases enhancing survival of LCH cells and promoting recruitment of inflammatory immune cells forming characteristic granulomatous lesions. These pathognomonic features result in the accumulation of LCH cells in any organ causing a wide range of clinical symptoms. Frontline therapy for LCH involves combination chemotherapy and steroidal anti-inflammatories, or MAPK inhibitors, which have significant toxicity and fail to eliminate disease causing precursors. New therapeutic approaches are urgently needed. Here, using multiple genetic mouse models, we show that normal epidermal Langerhans cells (LCs) depend on HDAC3 for their development, differentiation, and survival. Integrative RNA and chromatin-immunoprecipitation-sequencing show loss of HDAC3 abrogates the expression of master regulators of myeloid development and function including Csf1r, Spi1, Id2 and Runx3. LCH cells are also known to rely on Csf1r and Pu.1 for their development and homeostasis, thus we hypothesized that LCH cells similarly rely on HDAC3 for their development and survival. CD11c Cre LSL-BRAFV600E ( BRAFV600E CD11c) mice develop severe multifocal LCH with pronounced lesion development in their livers and lungs, hepatosplenomegaly, and a reduced lifespan due to the accumulation of pathological dendritic cells (DCs). We generated BRAFV600E CD11c HDAC3 fl/fl ( BRAFV600E HD3KO) mice, which produce pathological DCs that simultaneously express BRAFV600E and harbor a conditional deletion in the deacetylase domain of HDAC3. Compared to BRAFV600E CD11c mice, BRAFV600E HD3KO mice exhibited significantly less hepatosplenomegaly, reduced lesional burden (Panel A), attenuated disease progression, and improved survival indicating reduced LCH disease burden. Compared to BRAFV600E CD11c flow cytometry showed BRAFV600E HD3KO had reduced numbers of LCH cells in lungs and livers linking improved disease outcomes to abrogation of pathological DCs. Flow cytometric analysis of circulating myeloid cells further found reduced frequency of circulating DCs and DC progenitors, indicating that a lack of HDAC3 activity prevents the development of pathological DCs (Panel B). LCH-like cells can be generated in vitro by culturing BRAFV600E CD11c bone marrow with granulocyte-monocyte colony-stimulating factor (GM-CSF), providing a valuable drug screening tool. Treating LCH-like cells with RGFP966, an HDAC3-specific inhibitor, increased apoptosis indicated by annexin-V and DAPI staining, reduced expression of Bcl-2, increased CCR7 expression, and decreased S6 phosphorylation (an indication of decreased mTOR activity), showing that pharmacological inhibition of HDAC3 may prove therapeutically efficacious by abrogating pathognomonic features of LCH cells. Together, our findings identify HDAC3 as a critical epigenetic regulator for both healthy and pathological LCs. We further show, HDAC3 is required for multiple pathognomonic features of LCH cells and could be a promising drug target. Furthermore, if HDAC3 is required for the development of pathological DC and DC progenitors, HDAC3 blockade would address a great need in treatment of patients with LCH.

5.22 High Frequency of Neuropsychiatric Disorders and a Need for Treatment in Patients with FXAND Linked to FMR1 Gene Premutation Carriers

5.22 High Frequency of Neuropsychiatric Disorders and a Need for Treatment in Patients with FXAND Linked to FMR1 Gene Premutation Carriers

A cross-sectional survey of symptoms and daily living among patients with polycythemia vera and their treating physicians in Japan

ABSTRACTObjectivesThis Japanese cross-sectional survey evaluated the symptoms, daily living activities, and treatment needs of patients with polycythemia vera (PV), as perceived by patients themselves and their physicians.MethodsThe study was conducted at 112 centers (March to July 2022) and included PV patients aged ≥20 years (n = 265) and their attending physicians (n = 151). The patient and physician questionnaires included 34 and 29 questions, respectively, to assess daily living, PV symptoms, treatment goals, and physician-patient communication.ResultsConcerning daily living (primary endpoint), work (13.2%), leisure activities (11.3%), and family life (9.6%) were most affected by PV symptoms. Patients aged <60 years more frequently reported an impact on daily living than patients aged ≥60 years. Some patients (30%) reported anxiety about their future condition. The most common symptoms were pruritus (13.6%) and fatigue (10.9%). Pruritus was ranked as the first treatment need for patients, while physicians ranked it fourth. Concerning treatment goals, physicians prioritized thrombosis/vascular event prevention, while patients prioritized delaying PV progression. Physicians were less satisfied with physician-patient communication than patients.ConclusionsPatients’ daily living was largely affected by PV symptoms. There are differences in physician and patient perceptions of symptoms, daily living, and treatment needs in Japan.Trial registrationUMIN Japan identifier: UMIN000047047.

Perspectives on relapse prevention following intensive treatment of anorexia nervosa: A focus group study.

Including the perspectives of individuals with lived experience of mental health issues is a critical step in research and treatment development. Focus groups with patients with a history of treatment for anorexia nervosa (AN) were conducted in anticipation of a clinical trial of Relapse Prevention and Changing Habits (REACH+). Seven female adults (23-51 years) who had previously received inpatient treatment for AN, now in remission, participated in one of two semistructured focus groups. Rapid qualitative analysis was used to examine participants' contributions and identify common topics. Transcript analysis yielded three topics related to relapse prevention: (1) recovery aids, including a sense of agency in treatment decisions and finding new interests/passions, (2) recovery hindrances, such as lack of access to care, and (3) identification of members of support system. Aspects of REACH+ received positive feedback, such as continuity of care from the inpatient setting and the use of telehealth. Viewpoints differed with respect to the helpfulness of obtaining patient weights in treatment. The REACH+ online platform received positive comments regarding content and usability, as well as suggestions for additional content. Qualitative feedback from patients with a history of AN highlighted the value of engaging patients in their own treatment decisions, as well as in treatment design and innovation. Within this small group, there were differences of opinion about treatment components, specifically weight assessment, that suggest the need for further data. User-centered design provides opportunities to improve the acceptability and, therefore, dissemination of novel treatments. Relapse prevention is a critical treatment need for patients with anorexia nervosa, as this illness too often follows a protracted course. There are challenges in both obtaining specialized care and in retaining patients in treatment. Here, patient perspectives on these challenges offer input to allow for optimization of relapse prevention treatment. Shared decision-making may be particularly valuable to support an individual's sense of agency and engagement in care.

Perimenopozal dönemin kalp yetersizliği seyrine etkileri

Purpose: It is known that the decrease in estrogen level in women's life has negative effects on the cardiovascular system. In this study, it was aimed to elucidate the changes in the clinical status and treatment requirement of patients with heart failure (HF) during the menopausal transition period.&#x0D; Materials and Methods: A total of 26 patients followed up in the HF outpatient clinic between 2015–2020 were included in this retrospective, single-center study. Demographic data of the patients, New York Heart Association class, echocardiographic findings, routine biochemical parameters and HF signs, symptoms and therapies were examined. Data at the beginning of the menopause period and after 12 months were compared. &#x0D; Results: At the end of the 12-month follow-up, a statistically significant increase was found in the daily dose of furosemide (50.5 mg/day vs. 72.4 mg/day). While the mean heart rate of the patients was 80.4±20.1 beats/min at the beginning, it was 69.3±10.1 beats/min in the control visit. Echocardiographically measured left ventricular (LV) systolic diameters of the patients were significantly increased compared to baseline in the control visit (41.2±7.4 mm vs 45.8±7.0 mm,). &#x0D; Conclusion: The menopausal period caused an increase in the need for treatment in patients followed up with HF. Therefore, in evaluation of the patients with HF, it would be a useful approach to question the menopausal status in detail and to follow the patients more closely during the menopausal transition period.

Healthcare Resource Utilization and Costs of Relapsed or Refractory Patients with Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Treated with Ibrutinib

Introduction: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia among adults in the United States (US). First-line (1L) treatment includes targeted treatments like the Bruton's tyrosine kinase inhibitor ibrutinib. While treatment with ibrutinib can result in durable responses and improved survival, patients who progress while on ibrutinib have been shown to have a poor prognosis. However, there is currently limited literature describing the economic burden associated with ibrutinib failure. Therefore, this study was conducted to compare the healthcare resource utilization (HRU) and costs between patients with and without relapse/refractoriness (R/R) to ibrutinib in the US. Methods: Data from Optum Clinformatics DataMartTM (01/2007-03/2020) were used to identify adult patients with ≥2 medical encounters with a diagnosis code for CLL or small lymphocytic lymphoma (SLL) on different dates, ≥1 pharmacy claim for ibrutinib therapy as a single-agent or combination therapy (first dispensing was the index date), and ≥12 months of continuous enrollment pre-index date (baseline period). Patients with a diagnosis for mantle cell lymphoma or with evidence of anticancer therapy (antineoplastic, radiation, or cell therapy) during baseline were excluded. Patients were categorized as R/R to ibrutinib if they received treatment with another antineoplastic after switching/discontinuing ibrutinib; all remaining patients were considered not R/R to ibrutinib (i.e., remained on ibrutinib for the whole observation period, restarted ibrutinib, or discontinued ibrutinib treatment without initiating a different antineoplastic). Patients who died on ibrutinib or within 6 months of discontinuation without subsequent antineoplastic therapy were excluded. All-cause and CLL/SLL-related HRU and healthcare costs incurred from the index date to the earliest of death, end of data availability or insurance coverage were evaluated and then compared in the population R/R and not R/R to ibrutinib using adjusted rate ratios for HRU and adjusted cost differences for costs. P-value and 95% confidence interval (CI) were obtained from non-parametric bootstrap procedures. Results: Among 1,126 patients treated with ibrutinib, mean age was 72.5 years and 38.8% were female. Patients had a mean Quan-Charlson Comorbidity index of 3.4. Over 1.8 years of observation, patients treated with ibrutinib had mean (SD) 0.47 (0.80) all-cause inpatient stays, 0.67 (1.50) emergency room (ER) visits, and 28.4 (18.1) outpatient visits, resulting in $148,758 (77,099) per patient-year total all-cause healthcare costs. CLL/SLL-related HRU amounted to 0.37 (0.69) inpatient stays, 0.19 (0.48) ER visits, and 12.0 (10.8) outpatient visits, resulting in $29,079 (51,165) per patient-year CLL/SLL-related medical costs. A total of 207 patients were R/R to ibrutinib (mean age: 73.4 years; 40.1% female) and 919 were not R/R to ibrutinib (mean age: 72.3 years; 38.5% female). Over a mean observation of 2.4 years (R/R) and 1.8 years (not R/R), patients R/R to ibrutinib had significantly more all-cause inpatient stays (rate ratio [95% CI] = 1.92 [1.57, 2.37]; P<0.001), ER visits (1.81 [1.31, 2.61]; P<0.001), and outpatient visits (1.51 [1.38, 1.65]; P<0.001) than patients not R/R to ibrutinib (Table). This led to $16,427 (95% CI: 4,627, 28,103) significantly higher incremental all-cause healthcare costs per patient-year in the R/R cohort versus not R/R (P=0.006). Similarly, rates of CLL/SLL-related inpatient stays (rate ratio [95% CI] =1.91 [1.51, 2.40]; P<0.001), ER visits (1.93 [1.43, 2.66]; P<0.001), and outpatient visits (1.80 [1.62, 2.02]; P<0.001) were significantly higher among patients R/R to ibrutinib versus not R/R (Table). This resulted in $38,252 (95% CI: 30,505, 48,023) significantly higher incremental CLL/SLL-related medical costs per patient-year in the R/R cohort versus not R/R (P<0.001). Conclusions: In this US real-world study, patients with CLL who were treated with ibrutinib incurred substantial HRU and costs. This burden was shown to be even larger for patients who were R/R to ibrutinib, with CLL/SLL-related healthcare resource use being nearly twice higher for R/R compared to non-R/R patients. These findings highlight the unmet treatment need for patients with CLL who are R/R to ibrutinib. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Demonstration of a multidisciplinary approach on the example of assessing the psycho- vegetative state in patients with various courses of duodenal ulcer

The prevalenceand multifactorial etiology of duodenal ulcer disease (DUD) are of great interest to researchers. We have noticed that besidesthe usual symptoms of DUD, patients report aboutconditions what defi ned as a depressive episode, a decrease in quality of life, autonomic nervous system dysfunction, and sleep disorders. It was decided to compare the presence and severity of nonspecifi c symptoms in the complicated and uncomplicated form of DUD. We examined 110 patients divided into two groups of 55 people according to the form of the course of the disease. The examination included the collection of complaints, anamnesis, gastroenterologist’s examination, esophagogastroduodenoscopy, common blood test + glucose test, long-term monitoring of intragastric pH-metry, questionnaires for assessing the main nonspecifi c complaints of patients: HADS, questionnaire of the National Cardiologic Center of the Russian Academy of Medical Sciences in the Y. M. Rutgizer and A. G. Mikhailov’s modifi cation for patients with the digestive tract diseases, A. M. Vane and Ya. I. Levin’s questionnaire for scoring subjective sleep characteristics. We calculated the Kerdo index and used the A. D. Solovyova’s standard tables method, assessing autonomic dysfunction. We have obtained the following results: patients with a complicated course of DUD are diagnosed with depression twice as often as people with an uncomplicated course. Patients with a complicated course of DUD had the decreased quality of life almost twice as much. As for the departments of the autonomic nervous system imbalance, it was much more common in patients with a complicated form in comparison with the group of patients with an uncomplicated variant of DUD, sympathicotonia was represented by a large number of people. Appreciable sleep disorders were also associated with a complicated course of DUD. Comparing the parameters of the presence of a clinical or subclinical form of depression with the predominant variant of VT, we noticed a connection between depression and sympathicotonia with out reference to the complicated course of the disease. We should note that sleep disorders in DUD are diff erent from those in isolated depression. We found a link between a decrease in the quality of life and the need for treatment in patients with a complicated form of DUD; the disease severely restricts physical activity, as well as social and everyday aspects of life, which can lead to depression. A “viciouscircle” isforming.

Can the Brinkman Index Predict the Need for Treatment in Patients With COVID-19?

Can the Brinkman Index Predict the Need for Treatment in Patients With COVID-19?

Safety and Tolerability of Difelikefalin for the Treatment of Moderate to Severe Pruritus in Hemodialysis Patients: Pooled Analysis From the Phase 3 Clinical Trial Program

Rationale & ObjectiveWe report a pooled safety analysis of intravenous difelikefalin in participants with moderate to severe chronic kidney disease–associated pruritus (CKD-aP) treated by hemodialysis in 4 phase 3 clinical studies.Study DesignKALM-1 and KALM-2 were randomized, double-blind, placebo-controlled, pivotal phase 3 studies; CLIN3101 (52 weeks) and CLIN3105 (12 weeks) were open-label studies.Setting & ParticipantsAdults with moderate to severe CKD-aP treated by hemodialysis in North America, Europe, and the Asia-Pacific region.InterventionAt least 1 intravenous placebo or difelikefalin dose of 0.5 mcg/kg for up to 64 weeks.OutcomesSafety.ResultsSafety analyses were conducted with 848 participants in the placebo-controlled cohort (424 participants each in the difelikefalin and placebo groups) and in 1,306 participants in the all-difelikefalin-exposure cohort. In the placebo-controlled cohort, the most commonly reported treatment-emergent adverse events (TEAEs), occurring in ≥2% of participants receiving difelikefalin and with a ≥1% higher incidence than placebo, were diarrhea (9.0% and 5.7%, respectively); dizziness (6.8% and 3.8%, respectively); nausea (6.6% and 4.5%, respectively); gait disturbances, including falls (6.6% and 5.4%, respectively), hyperkalemia (4.7% and 3.5%, respectively); headache (4.5% and 2.6%, respectively); somnolence (4.2% and 2.4%, respectively); and mental status changes (3.3% and 1.4%, respectively). These were mostly mild or moderate, with few leading to discontinuation. Incidence rates of TEAEs, serious TEAEs, and discontinuations because of TEAEs did not increase with long-term exposure. Three participants (0.7%) in the difelikefalin group and 5 participants (1.2%) in the placebo group died during the study.LimitationsPooled data from studies with different designs.ConclusionsIntravenous difelikefalin demonstrated an acceptable safety profile, was generally well tolerated with long-term use, and may address the unmet treatment need for patients with CKD-aP treated by hemodialysis.FundingCara Therapeutics, Inc.Trial RegistrationKALM-1 is registered as NCT03422653, KALM-2 as NCT03636269, CLIN3101 as NCT03281538, and CLIN3105 as NCT03998163.

Tuboovaryan apseli hastalarda sistemik inflamatuvar belirteçlerin medikal tedavi başarısızlığını öngörmedeki yeri

Aim: Aimed to evaluate the role of systemic inflammatory markers and Aspartate aminotransferase to Platelet Ratio Index (APRI) sore in predicting medical treatment failure in patients with Tubo-ovarian abscess (TOA).&#x0D; Materials and Methods: Patients (n=240) hospitalized with a diagnosis of TOA between August 2016 - October 2020 were included in the study. Patients' demographic and clinical characteristics and mean C-Reactive protein (CRP) level, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and APRI score measured on admission were also recorded. The role of these parameters was investigated in predicting medical treatment failure in patients who only received medical treatment or who needed surgical treatment.&#x0D; Results: The mean age (40.95 ± 6.96 vs. 38.09 ± 7.69), abscess size (67.57 ± 19.86 mm vs. 52.78 ± 16.63 mm), CRP level, (140.61 ± 110.88 vs. 75.24 ± 36.64 mg/L), white blood cell count (13818.86 ± 5445.80 and 11845.31 ± 4424.39 μL), neutrophil count (11146.81 ± 5284.83 and 9242.03 ± 4278.60 μL) and NLR (9.52 ± 6.88 and 6.64 ± 6.30) of patients who received surgical treatment were significantly higher than those who received only medical treatment. In receiver operating characteristics (ROC) analysis area under the curve (AUC) 0.607 was statistically significant for CRP with a cut-off value of 11.57 to predict medical treatment failure (95% 0.531-0.682, sensitivity 63.3%, specificity 55.4%).&#x0D; Conclusion: NLR, PLR and APRI score are ineffective in predicting the need for surgical treatment. CRP could be used as a marker in predicting the need for surgical treatment in patients with TOA.

Factors affecting patient-acceptable symptom states and treatment decision in familial Mediterranean fever.

Familial Mediterranean fever [FMF] is the most common autoinflammatory disease characterized by inflammatory attacks of fever and polyserositis. Patients' quality of life is significantly affected due to recurrent excruciating pain attacks and complications. This study is performed to evaluate the parameters most affecting patients' satisfaction from treatment. : Three hundred and forty-six consecutive patients diagnosed with FMF were enrolled in this study. Current treatment, acute phase proteins, number, type, and severity of predominant attacks, absenteeism from work/school in the last three months were recorded, and the participants were asked whether they needed additional treatment to evaluate Patient Acceptable Symptom State (PASS) status. Mean age of the overall group was 38.2 ± 11.7 years (62.4% female, 37.6% male). Two hundred and twenty-seven patients were treated with colchicine, 97 patients with colchicine plus Interleukin-1 (IL-1) antagonist, and 22 only with IL-1 antagonist (67.1%, 26.3%, 6.64% in order). Of the overall group, 33.8% (n = 117) believed to need additional treatment options. Additional treatment need of patients was significantly affected by work impairment due to attacks, absent days from work, disease activity, the discomfort of patients during attacks, the number of attacks, and treatment options; but not by the level of acute-phase proteins between attacks. PASS score is significantly related to clinical parameters and quality of life. Patients' PASS scores and treatment choices are notably affected by the severity and frequency of attacks and absenteeism from work/school. Clinical activity and quality of life should be evaluated at every visit to provide patients' satisfaction with treatment.

Dental Aesthetic Index (Dai) Score Among Patients with Antero-Posterior Basal Bone Discrepancy

Aim: To determine the mean Dental Aesthetic Index (DAI) malocclusion score among patients with Antero-posterior basal bone discrepancy (APBBD) and to assess the treatment need of the patients with horizontal jaw deformities as calculated by DAI guidelines. Methodology: The descriptive cross sectional study was conducted in the Orthodontic department, University College of Dentistry, The University of Lahore. Lateral cephalograms of the patients were analyzed for anteroposterior basal bone discrepancy by measuring angle ANB. Two hundred and thirty one subjects were included in the study having ANB &gt;4° or &lt;1° through non probability consecutive sampling technique. Study casts were obtained and malocclusion parameters for Dental Aesthetic Index (DAI) were calculated. Results: The mean Dental Aesthetic Index (DAI) score in APBBD was 37.10 ± 7.62, in skeletal class II (37.14 ± 7.90) and in skeletal class III (36.98 ± 6.68), (p-value 0.75). Moderate positive correlation existed between DAI score and ANB in skeletal class II subjects (R 0.49, p &lt;0.001). Conclusion: The mean DAI score in APBBD showed mandatory treatment need in patients with Antero-posterior basal bone discrepancy. Moderately positive correlation existed between ANB and DAI score in skeletal class II patients. Keywords: Malocclusion, Dental Aesthetic Index, Jaw disharmony

Frequency of the necessity of dentoalveolar surgery or conservative treatment in patients before kidney transplantation depending on the duration of dialysis and causative nephrological disease

ObjectivesThis retrospective study evaluates intraoral surgical and conservative treatment need in patients with a chronic kidney end-stage disease, depending on the duration of dialysis treatment and the causative nephrological disease.Material and methodsThis study is based on data of patients referred to the Department of Oral and Maxillofacial Surgery of the University Hospital Erlangen, Germany, prior to kidney transplantation between January 2015 and March 2020. The necessity for oral surgical or dental therapy was determined by clinical and radiological examinations. Data on renal replacement therapy, cause of underlying renal disease, lifestyle, and general health were collected.ResultsData of N = 89 patients demonstrated that surgical treatment need depends on dialysis duration (p = 0.042). Patients, who had been dialyzing for 2 to 3 years showed the highest need for surgical intervention (80.0%; p = 0.024), followed by dialysis patients with a dialysis time of more than 3 years (48.1%). Similarly, dialysis patients in the second or third year of dialysis had the highest need for conservative treatment (73.3%; p > 0.05), followed by 55.6% of dialysis patients in the third year of dialysis.ConclusionsOperative and conservative treatment is essential to optimize subsequent kidney transplantation. The greatest necessity could be detected for patients in the second and third years of dialysis.Clinical relevanceOral health addressing surgical and conservative treatment need depends on the duration of dialysis in patients with a chronic kidney end-stage disease.