Difficult Disease Research Articles

EXTH-25. OPTIMIZATION OF NEW CHEMOTHERAPEUTIC AGENTS BY INTRA-ARTERIAL INFUSION IN GLIOBLASTOMAS

Abstract Being the most aggressive malignant primary brain tumor, glioblastoma (GBM) is a difficult disease to treat. The first line treatment is well established, but most patients will relapse before or during the treatments. The overall survival is only 14,6 months while the progression-free survival is 6,9 months. In Sherbrooke, Dr Fortin prioritize the intra-arterial (IA) administration of chemotherapeutic agents (CTA) as a second line treatment. Unfortunately, certain patients will not respond or will even develop chemoresistance to the agents. Therefore, there is a strong need for bringing more CTAs onto clinical care. The maximal tolerable dosage (MTD) of every agent was first determined. Every CTAs were then administered IA by retrograde infusion in the external carotid but also intravenously (IV) by the caudal vein. We used the Fischer-F98 glioma rat model in our studies. For the efficacy study, we implanted 10 000 F98 cells into their brain. After 10 days, they received the treatment associated to their group. The animals were followed every day and were euthanized when their condition was too deteriorated. The dosages found in the MTD study for topotecan and cytarabine was 4 mg/kg and 8,75 mg/kg respectively while paclitaxel was too toxic. As for the efficacy study, the IA group of topotecan showed a promising outcome with a higher survival rate (29 days) compared to the IV one (23,5 days). As for the cytarabine, the opposite was observed (IA: 22 days, IV: 26,5 days). While topotecan and cytarabine could be given intra-arterially, only topotecan showed conclusive results. More animals will be added to this group to confirm this outcome. Cytarabine is not a good option since the IV group survived a longer time than the IA group. As for the paclitaxel, the intra-tumoral infusion will be tested to see if we can get positive results.

IPNA consensus definitions for clinical trial outcomes in steroid-resistant nephrotic syndrome.

Assessment of the true impact of therapeutic interventions is a challenge in the absence of universal, standardized definitions for clinical trial endpoints in children with kidney diseases. Steroid-resistant nephrotic syndrome (SRNS) is a difficult kidney disease to treat, with unremitting disease progressing to kidney failure. Currently, available therapies result in suboptimal cure rates. Clinical trials with innovative, targeted treatments will likely be conducted for this disease in the foreseeable future. An international consortium of the IPNA Best Practices and Standards Committee and the Pediatric Nephrology Expert Group of the conect4children (c4c) network developed through consensus, standardized, internationally acceptable definitions for trial outcomes for SRNS. The endpoint definitions were formulated for use with urine protein to creatinine ratios and estimated glomerular filtration rates. Definitions of complete remission, partial remission, non-remission of disease, reduction in proteinuria, kidney disease progression, kidney failure, and composite kidney outcome were refined using an iterative process until a consensus was achieved.

The Deceptive Reassurance of a "Negative" Test - A Difficult Case Highlighting the BioFire© Meningitis/Encephalitis Panel and Medical Heuristics.

Purpose: Neurolisteriosis is a difficult neurologic infectious disease to diagnose. Here, we present a case in which the diagnosis was suspected, but repeated testing for the pathogen was negative. Ultimately the diagnosis was made after the patient iatrogenically worsened. Results: This prompted an investigation into the widely used diagnostic test, the BioFire© Meningitis/Encephalitis Panel. Although the company reports high sensitivities and specificities for the panel, real world studies have demonstrated insufficient evidence that all 14 pathogens tested on the panel have similar results. Conclusion: This case is a reminder of the heuristics involved in medicine and how with every medical advancement, clinicians should always go back to the fundamentals of history-taking and physical examinations to ensure no steps have been overlooked in the diagnosis and management of challenging cases.

Pharmacological Management of Acute and Chronic Insomnia: A Cross-Sectional Study

Objective Insomnia is a frequent and difficult disease to treat. The objective was to determine the pharmacological management of a group of patients diagnosed with acute and chronic insomnia. Methods This is a cross-sectional study that identified patterns of prescription of drugs for outpatient use in patients with insomnia from a population database of 8.5 million individuals in the Health System of Colombia. Sociodemographic and pharmacological variables were considered. Results A total of 5825 patients with insomnia were identified. Acute insomnia was the most frequent complaint (85.2%). A total of 76.9% received pharmacological treatment, mainly through off-label drugs (70.7%), such as trazodone (20.2%), quetiapine (12.3%), and clonazepam (11.1%). The approved drugs were used in 9.9% of the patients, especially eszopiclone (4.7%) and zopiclone (3.6%). Benzodiazepines and Z compounds predominated in the elderly and individuals with chronic insomnia. Conclusions The pharmacological treatment of insomnia in this group of patients is heterogeneous, and medications not approved for this indication are very frequently used.

Trend in Infective Endocarditis in Bulgaria: Characteristics and Outcome, 17-Years, Single Center Experience.

Infective endocarditis (IE) remains a difficult disease to diagnose and treat, with a persistently high mortality rate. There is a lack of recent data on IE in Bulgaria over the last decades. This study is retrospective, single-centered, and includes 270 patients diagnosed with IE for the period 2005-2021. We compared two periods, 2005-2015 (n = 119) and 2016-2021 (n = 151), to find the characteristics changes. The study included 177 (65.5%) male patients. In the second period, there is a significant increase in age from 62 (44-73) to 67 (53-75), (p = 0.023); in the Charlson comorbidities index (CCI) from 3 (1-4) to 4 (2-6), (p = 0.000); in cases with chronic kidney diseases (CKDs) from 15 (12.6%) to 55 (36.9%), (p = 0.001); coronary arterial diseases (CADs) from 20 (16.85%) to 44 (29.1%), (p = 0.018); and atrial fibrillation (AF) from 13 (10.9%) to 36 (23.8%), (p = 0.006). Ejection fraction decreased significantly in the second period from 63 (56-70) to 59 (51-66), (p = 0.000). Almost half of the patients 123 (45.6%) had no known predisposing cardiac condition, and 125 (46.3%) had an unknown port of entry. IE was community-acquired in 174 (64.4%), healthcare-associated in 72 (26.7%), and injection-drug-use-related IE in 24 (8.9%). The study population included 183 (67.8%) native valve IE, 85 (31.5%) prosthetic IE, and 2 (0.74%) intracardiac-device-related IE. The hemocultures were positive in 159 (59.6%), and the most frequent pathogenic agent was staphylococci-89 (33.3%) (Staphylococcus aureus-44 (16.5%) and coagulase negative staphylococci-45 (16.8%)). Only 54 (20%) of patients underwent early surgery. The all-cause 30-day mortality rate was 67 (24.8%). There is no significant difference between the two periods in terms of the characteristics listed above. The profile of IE in Bulgaria has changed with increasing age and comorbidity, changing predisposing cardiac conditions, and entry door. The most common pathogen was the Staphylococcus spp. The 30-day mortality rate remains high.

Hydrogen peroxide responsive theranostics for cancer-selective activation of DNA alkylators and real-time fluorescence monitoring in living cells

Triple negative breast cancer (TNBC) is a notoriously difficult disease to treat, and many of the existing TNBC chemotherapeutics lack tumor selectivity and the capability for simultaneously visualizing and monitoring their own activity in the biological context. However, TNBC cells have been known to generate high levels of reactive oxygen species (ROS), such as hydrogen peroxide (H2O2). To this end, three novel small molecule theranostics 1a, 1c, and 2 consisting of both H2O2-responsive nitrogen mustard prodrug and profluorophore character have been designed, synthesized, and evaluated as targeted cancer therapeutics and bioimaging agents. The three theranostics comprise of boronate esters that deactivate nitrogen mustard functional groups and fluorophores but allow their selective activation through H2O2-specific oxidative deboronation for the release of the active drug and fluorophore. The three theranostics demonstrated H2O2-inducible DNA-alkylating capability and fluorescence turn-on properties in addition to selective anticancer activity. They are particularly effective in killing TNBC MDA-MB-468 cells with high H2O2 level while safe to normal epithelial MCF-10A cell. The conjugated boron-masked fluorophores in 1c and 2 are highly responsive towards H2O2, which enabled tracking of the theranostics in living cellular mitochondria and nucleus organelles. The three theranostics 1a, 1c, and 2 are capable of both selective release of the active drug to take effect in H2O2-rich cancer sites and simultaneously monitoring its activity. This single molecule system is of utmost importance to understand the function, efficacy, and mechanism of the H2O2-activated prodrugs and theranostics within the living recipient.

Customized voluntary waiting period before first insemination in primiparous dairy cows: Effect on milk production, fertility, and health

A customized voluntary waiting period (VWP) before first insemination was tested in 18 commercial dairy herds in Sweden to assess milk production, fertility, and health in primiparous cows expected to be suited for extended VWP. Cow selection for extended VWP was based on 3 criteria in early lactation: (1) the 10% of cows with highest genomic persistency index, (2) cows with a difficult calving or disease during the first month of lactation, and (3) cows with higher yield during d 4 to 33 after calving than the herd average for primiparous cows. Cows meeting at least one of these criteria were randomly assigned to either treatment with an extended VWP of at least 175 d (ExtExt; n = 174, calving interval [CInt] = 16.3 mo) or treatment with a conventional VWP of a maximum of 100 d; (ExtConv; n = 173, CInt = 12.4 mo). Cows not meeting any of the criteria were assigned to the conventional VWP treatment (ConvConv; n = 183, CInt = 12.0 mo). We found no differences in milk yield per day in the CInt between treatments, although 305-d and whole-lactation (WL) milk yields were higher for ExtExt cows (10,371 and 13,803 kg) than ExtConv cows (9,812 and 10,257 kg). Milk yield at the last test milking before dry-off was lower in ExtExt compared with ExtConv cows (24.9 vs. 28.3 kg), but the results showed no difference in dry period length between the treatments. Regarding reproductive performance, the ExtExt cows had a higher first service conception rate (FSCR; 60% vs. 45%) and lower number of inseminations per conception (NINS; 1.67 vs. 2.19), compared with the ExtConv cows. As expected, ConvConv cows had the lowest milk yield (305-d, WL, and per day) in the CInt; however, FSCR and NINS did not differ between ConvConv cows and cows in the other 2 VWP treatments. Disease incidence was higher for cows in the ExtConv compared with the ConvConv treatment, but there was no difference between ExtExt and the 2 other VWP treatments. Further, no difference in the proportion of cows with good udder health or culling rate was detected between any of the treatments, though due to low prevalence, the study lacked power to draw major conclusions on these results. Thus, prolonging VWP for suitable primiparous cows can produce benefits such as improved fertility in the form of higher FSCR and lower NINS, as well as lower dry-off yield, without compromising milk yield or prolonging dry period length.

Pancreatic cancer and sarcopenia: a narrative review of the current status.

Pancreatic cancer is still a difficult disease to treat, despite recent advances in surgical techniques and chemotherapeutic drugs. Its incidence continues to rise, as does the number of older patients. Sarcopenia is defined as a progressive and generalized loss of skeletal muscle mass and strength. Sarcopenia is present in approximately 40% in patients with pancreatic cancer. Sarcopenia is primarily diagnosed through imaging, and progress is being made in the development of automated methods and artificial intelligence, as well as biomarker research. Sarcopenia has been linked to a poor prognosis in pancreatic cancer patients. However, some studies suggest that sarcopenia is not always associated with a poor prognosis, depending on the resectability of pancreatic cancer and the nature of treatment, such as surgery or chemotherapy. Recent meta-analyses have found that sarcopenia is not linked to postoperative complications. It is still debated whether there is a link between sarcopenia and drug toxicity during chemotherapy. The relationship between sarcopenia and immunity has been investigated, but the mechanism is still unknown.

Tumor regression following autologous tumor lysate-loaded dendritic cell vaccination immunotherapy: illustrative case.

Despite years of research, the standard of care (SOC) treatment for grade 4 glioma has remained virtually unchanged for the last 2 decades. Autologous tumor lysate-loaded dendritic cell vaccination (DCVax-L), a novel immunotherapy, has demonstrated a significant survival benefit in a phase 3 trial. A 34-year-old male presented with episodes of lightheadedness and was subsequently diagnosed with a large fronto-insulo-temporal tumor, likely to be high grade. He underwent an asleep craniotomy for debulking, with a residual tumor noted in the frontal lobe and amygdala. Tumor histopathology was reported as isocitrate dehydrogenase (IDH) mutant methylated grade 4 astrocytoma. He received SOC treatment, alongside a course of DCVax-L. Surveillance imaging showed cystic transformation followed by a reduction in size of the residual tumor in the frontal lobe; the residual in the amygdala had regressed entirely. The patient remained clinically well and had returned to his preoperative functionality. The authors report a patient with grade 4 astrocytoma who received DCVax-L treatment in addition to SOC adjuvant therapy. The pattern and extent of tumor regression are highly unusual and atypical for what is seen or expected with adjuvant SOC treatment alone. The addition of DCVax-L to SOC opens new avenues in the management of this difficult disease. https://thejns.org/doi/10.3171/CASE24112.

The Markov Chains to Predict Malaria Incidence and Death in Gazira State, Sudan From 2001 to 2021

Background: Malaria is considered the most deadly and difficult parasitic disease in the world. This study aims to use Markov chains to predict the probability patterns of stability or change in malaria incidence and deaths. Methods: Markov chains were used to analyze the data on malaria incidence and deaths through the Windows Quantitative Systems for Business (WINQSB) program. Data was obtained from the Ministry of Health, Gazira State, Health Information Centre, Sudan. The data is a time series, from 2001 to 2021 per year, according to three cases of decrease, stability, and increase. A transitional matrix is built for the three cases. Results: The results revealed that the probability that malaria incidence and deaths will reach a stable state in one year and in the long run; the probability of transitioning to an increased state was 0.66 of malaria incidence; and the probability of moving to a decreased state was 0.52 of malaria deaths. Conclusion: The results show that the malaria incidence will increase and malaria deaths will decrease in the short and long run from 2022 to 2030 in Gazira State. It is necessary to reinforce means and resources for case management and to investigate the determinants of the situation. Thus, strategies are urgently needed to arrest the unacceptably high incidence and death rates. Keywords: Markov Chain, Predicting, Malaria Incidence, Malaria Death, Gazira State.

Stem Cells and Stem Cell-Derived Factors for the Treatment of Inflammatory Bowel Disease with a Particular Focus on Perianal Fistulizing Disease: A Minireview on Future Perspectives.

Inflammatory bowel disease remains a difficult disease to effectively treat, especially fistulizing Crohn's disease. Perianal fistulas in the setting of Crohn's disease remain an area of unmet need with significant morbidity in this patient population. Up to one third of Crohn's patients will have perianal fistulizing disease and current medical and surgical interventions are of limited efficacy. Thus, most patients experience significant morbidity, narcotic use, and loss of employment and end up with multiple surgical interventions. Mesenchymal stem cells (MSCs) have shown efficacy in phase 3 clinical trials, but considerable infrastructure challenges make MSCs limited with regard to scalability in clinical practice. Extracellular vesicles, being derived from MSCs and capturing the secretome functionality of MSCs, offer similar physiological utility regarding mechanism, while also providing an off the shelf regenerative medicine product that could be widely used in daily clinical practice.

Genital Tuberculosis as a Socially Significant Disease (Literature Review)

Globally, TB is the second leading cause of death from infectious diseases after COVID-19. Tuberculosis of the female genital organs is a type of extrapulmonary tuberculosis.It is known that both clinically pronounced and latent forms of this disease can cause both primary and secondary infertility due to pathogenetically caused disruption of the structure of the fallopian tubes and changes in the susceptibility of the uterine endometrium. It can be assumed that the problem of genital tuberculosis in Russia is still very relevant, although its true prevalence is unknown. This assumption is based on the facts of the projected growth of indicators the incidence of extrapulmonary tuberculosis, the obvious discrepancy between the real incidence and the official figures, as well as the increasing incidence of tubal-peritoneal infertility, which is often caused by genital tuberculosis. It is known that tuberculosis of the female genital organs is a difficult disease to diagnose. This is determined, in particular, by the fact that it does not have specific (so-called "marker") manifestations. Low rates of diagnosis of extrapulmonary forms of TB create a false sense of well-being, which does not reflect its true epidemiological picture. An obvious need today is the development of an optimal diagnostic complex, the use of which would contribute to accelerating the diagnosis of genital tuberculosis in women and, as a result, preventing the occurrence of irreversible changes in the female reproductive system caused by it. The authors used the scientific databases CyberLeninka, ELibrary and PubMed. Articles were searched for the following keywords: "tuberculosis", "genital tuberculosis", "infertility and tuberculosis". The paper analyzes articles published over the past 10 years.

Bronchial Asthma and COVID-19: Etiology, Pathological Triggers, and Therapeutic Considerations.

Bronchial asthma (BA) continues to be a difficult disease to diagnose. Various factors have been described in the development of BA, but to date, there is no clear evidence for the etiology of this chronic disease. The emergence of COVID-19 has contributed to the pandemic course of asthma and immunologic features. However, there are no unambiguous data on asthma on the background and after COVID-19. There is correlation between various trigger factors that provoke the development of bronchial asthma. It is now obvious that the SARS-CoV-2 virus is one of the provoking factors. COVID-19 has affected the course of asthma. Currently, there is no clear understanding of whether asthma progresses during or after COVID-19 infection. According to the results of some studies, a significant difference was identified between the development of asthma in people after COVID-19. Mild asthma and moderate asthma do not increase the severity of COVID-19 infection. Nevertheless, oral steroid treatment and hospitalization for severe BA were associated with higher COVID-19 severity. The influence of SARS-CoV-2 infection is one of the protective factors. It causes the development of severe bronchial asthma. The accumulated experience with omalizumab in patients with severe asthma during COVID-19, who received omalizumab during the pandemic, has strongly suggested that continued treatment with omalizumab is safe and may help prevent the severe course of COVID-19. Targeted therapy for asthma with the use of omalizumab may also help to reduce severe asthma associated with COVID-19. However, further studies are needed to prove the effect of omalizumab. Data analysis should persist, based on the results of the course of asthma after COVID-19 with varying degrees of severity.

Novel drug discovery: Advancing Alzheimer's therapy through machine learning and network pharmacology

Alzheimer's disease (AD), marked by tau tangles and amyloid-beta plaques, leads to cognitive decline. Despite extensive research, its complex etiology remains elusive, necessitating new treatments. This study utilized machine learning (ML) to analyze compounds with neuroprotective potential. This approach exposed the disease's complexity and identified important proteins, namely MTOR and BCL2, as central to the pathogenic network of AD. MTOR regulates neuronal autophagy and survival, whereas BCL2 regulates apoptosis, both of which are disrupted in AD. The identified compounds, including Armepavine, Oprea1_264702,1-cyclopropyl-7-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid,(2S)-4′-Hydroxy-5,7,3′-trimethoxyflavan,Oprea1_130514,Sativanone,5-hydroxy-7,8-dimethoxyflavanone,7,4′-Dihydroxy-8,3′-dimethoxyflavanone,N,1-dicyclopropyl-6,Difluoro-Methoxy-Gatifloxacin,6,8-difluoro-1-(2-fluoroethyl),1-ethyl-6-fluoro-7-(4-methylpiperidin-1-yl),Avicenol C, demonstrated potential modulatory effects on these proteins. The potential for synergistic effects of these drugs in treating AD has been revealed via network pharmacology. By targeting numerous proteins at once, these chemicals may provide a more comprehensive therapeutic approach, addressing many aspects of AD's complex pathophysiology. A Molecular docking, dynamic simulation, and Principle Component Analysis have confirmed these drugs' efficacy by establishing substantial binding affinities and interactions with important proteins such as MTOR and BCL2. This evidence implies that various compounds may interact within the AD pathological framework, providing a sophisticated and multifaceted therapy strategy. In conclusion, our study establishes a solid foundation for the use of these drugs in AD therapy. Thus current study highlights the possibility of multi-targeted, synergistic therapeutic approaches in addressing the complex pathophysiology of AD by integrating machine learning, network pharmacology, and molecular docking simulations. This holistic technique not only advances drug development but also opens up new avenues for developing more effective treatments for this difficult and widespread disease.

Newly Diagnosed HIV Infection in Patients with Progressive Multifocal Leukoencephalopathy (Literature Review and Clinical Cases)

In recent years, in the Kyrgyz Republic, HIV infection is more often detected at an advanced stage based on of advanced opportunistic infections. Late detection of people living with HIV causes disability and death due to untimely initiation of antiretroviral therapy and late prevention of opportunistic infections. The most difficult secondary disease to diagnose in the advanced stage of HIV infection is progressive multifocal leukoencephalopathy, often with an unfavorable outcome. This article presents two newly identified clinical cases of HIV infection in patients with difficult-to-diagnose progressive multifocal leukoencephalopathy, which may increase doctors' alertness to these diseases.

Exploring non-coding RNA mechanisms in hepatocellular carcinoma: implications for therapy and prognosis.

Hepatocellular carcinoma (HCC) is a significant contributor to cancer-related deaths in the world. The development and progression of HCC are closely correlated with the abnormal regulation of non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Important biological pathways in cancer biology, such as cell proliferation, death, and metastasis, are impacted by these ncRNAs, which modulate gene expression. The abnormal expression of non-coding RNAs in HCC raises the possibility that they could be applied as new biomarkers for diagnosis, prognosis, and treatment targets. Furthermore, by controlling the expression of cancer-related genes, miRNAs can function as either tumor suppressors or oncogenes. On the other hand, lncRNAs play a role in the advancement of cancer by interacting with other molecules within the cell, which, in turn, affects processes such as chromatin remodeling, transcription, and post-transcriptional processes. The importance of ncRNA-driven regulatory systems in HCC is being highlighted by current research, which sheds light on tumor behavior and therapy response. This research highlights the great potential of ncRNAs to improve patient outcomes in this difficult disease landscape by augmenting the present methods of HCC care through the use of precision medicine approaches.

Applications of nanomaterials in medicine against cancer

Nowadays, all walks of life are developing with innovation at their core, and the subject of materials is no exception, while nanomaterials occupy an important position in the emerging field due to their unique properties and wide coverage. In addition, the incidence of cancer, a difficult disease with a very high mortality rate, is increasing day by day. Therefore, research on cancer has received extensive attention from society. Therefore, this paper explores how cancer can be treated by means of nanomaterials through the organization of current research and papers in the field. Research at this stage suggests that nanomaterials play a major auxiliary role in anti-cancer technology, as follows: enhancing the ability of other substances to disrupt cell membranes, assisting in the delivery of anti-tumor drugs, improving imaging capabilities, and enhancing the ability of some substances to inhibit tumor growth through specific mechanisms. In future research, the focus will be on minimizing the side effects of the treatment and improving its safety.

“Hypertension is such a difficult disease to manage”: federally qualified health center staff- and leadership-perceived readiness to implement a technology-facilitated team-based hypertension model

BackgroundDespite decades of evidence demonstrating the efficacy of hypertension care delivery in reducing morbidity and mortality, a majority of hypertension cases remain uncontrolled. There is an urgent need to elucidate and address multilevel facilitators and barriers clinical staff face in delivering evidence-based hypertension care, patients face in accessing it, and clinical systems face in sustaining it. Through a rigorous pre-implementation evaluation, we aimed to identify facilitators and barriers bearing the potential to affect the planned implementation of a multilevel technology-facilitated hypertension management trial across six primary care sites in a large federally qualified health center (FQHC) in New York City.MethodsDuring a dedicated pre-implementation period (3–9 months/site, 2021–2022), a capacity assessment was conducted by trained practice facilitators, including (1) online anonymous surveys (n = 124; 70.5% of eligible), (2) hypertension training analytics (n = 69; 94.5% of assigned), and (3) audio-recorded semi-structured interviews (n = 67; 48.6% of eligible) with FQHC leadership and staff. Surveys measured staff sociodemographic characteristics, adaptive reserve, evidence-based practice attitudes, and implementation leadership scores via validated scales. Training analytics, derived from end-of-course quizzes, included mean score and number attempts needed to pass. Interviews assessed staff-reported facilitators and barriers to current hypertension care delivery and uptake; following audio transcription, trained qualitative researchers employed a deductive coding approach, informed by the Consolidated Framework for Implementation Research (CFIR).ResultsMost survey respondents reported moderate adaptive reserve (mean = 0.7, range = 0–1), evidence-based practice attitudes (mean = 2.7, range = 0–4), and implementation leadership (mean = 2.5, range = 0–4). Most staff passed training courses on first attempt and demonstrated high scores (means > 80%). Findings from interviews identified potential facilitators and barriers to implementation; specifically, staff reported that complex barriers to hypertension care, control, and clinical communication exist; there is a recognized need to improve hypertension care; in-clinic challenges with digital tool access imposes workflow delays; and despite high patient loads, staff are motivated to provide high-quality cares.ConclusionsThis study serves as one of the first to apply the CFIR to a rigorous pre-implementation evaluation within the understudied context of a FQHC and can serve as a model for similar trials seeking to identify and address contextual factors known to impact implementation success.Trial registrationClinicalTrials.gov NCT03713515, date of registration: October 19, 2018.

Italian National Registry of Alopecia Areata: an epidemiological study of 699 Italian patients.

Alopecia areata (AA) is an organ-specific autoimmune disease that affects the hair follicles of the scalp and the rest of the body causing hair loss. Due to the unpredictable course of AA and the different degrees of severity of hair loss, only a few well-designed clinical studies with a low number of patients are available. Also, there is no specific cure, but topical and systemic anti-inflammatory and immune system suppressant drugs are used for treatment. The need to create a global registry of AA, comparable and reproducible in all countries, has recently emerged. An Italian multicentric electronic registry is proposed as a model to facilitate and guide the recording of epidemiological and clinical data and to monitor the introduction of new therapies in patients with AA. The aim of this study was to evaluate the epidemiological data of patients with AA by collecting detailed information on the course of the disease, associated diseases, concomitant and previous events, and the clinical response to traditional treatments. Estimate the impact on the quality of life of patients. The creation of the National Register of AA has proven to be a valid tool for recording, with a standardized approach, epidemiological data, the trend of AA, response to therapies and quality of life. AA is confirmed as a difficult hair disease to manage due to its unpredictable course and, in most cases, its chronic-relapsing course, capable of having a significant impact on the quality of life of patients.

The Enigma of Rhupus Syndrome: A Case Report on Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA) Convergence

Rhupus syndrome is an uncommon and difficult clinical disease that results from the co-occurrence of Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE). There is an underdiagnosis of rhupus cases because the overlapping symptoms of both conditions frequently do not match the standard diagnostic criteria for autoimmune disorders. The neurological and physiological difficulties linked to this complex illness have a substantial impact on the health-related quality of life of patients. Pain, swelling, stiffness, deformities, and varied degrees of functional impairment are among the signs that must be identified in order to diagnose rhupus clinically. The clinical information of a young male exhibiting rheumatoid arthritis symptoms is presented in this case report. For a proper diagnosis and efficient treatment, it is essential to comprehend and deal with the complexity of rheumatoid arthritis