Definition Of Disease Research Articles

A Digital Tool for Clinical Evidence–Driven Guideline Development by Studying Properties of Trial Eligible and Ineligible Populations: Development and Usability Study

Background Clinical guideline development preferentially relies on evidence from randomized controlled trials (RCTs). RCTs are gold-standard methods to evaluate the efficacy of treatments with the highest internal validity but limited external validity, in the sense that their findings may not always be applicable to or generalizable to clinical populations or population characteristics. The external validity of RCTs for the clinical population is constrained by the lack of tailored epidemiological data analysis designed for this purpose due to data governance, consistency of disease or condition definitions, and reduplicated effort in analysis code. Objective This study aims to develop a digital tool that characterizes the overall population and differences between clinical trial eligible and ineligible populations from the clinical populations of a disease or condition regarding demography (eg, age, gender, ethnicity), comorbidity, coprescription, hospitalization, and mortality. Currently, the process is complex, onerous, and time-consuming, whereas a real-time tool may be used to rapidly inform a guideline developer’s judgment about the applicability of evidence. Methods The National Institute for Health and Care Excellence—particularly the gout guideline development group—and the Scottish Intercollegiate Guidelines Network guideline developers were consulted to gather their requirements and evidential data needs when developing guidelines. An R Shiny (R Foundation for Statistical Computing) tool was designed and developed using electronic primary health care data linked with hospitalization and mortality data built upon an optimized data architecture. Disclosure control mechanisms were built into the tool to ensure data confidentiality. The tool was deployed within a Trusted Research Environment, allowing only trusted preapproved researchers to conduct analysis. Results The tool supports 128 chronic health conditions as index conditions and 161 conditions as comorbidities (33 in addition to the 128 index conditions). It enables 2 types of analyses via the graphic interface: overall population and stratified by user-defined eligibility criteria. The analyses produce an overview of statistical tables (eg, age, gender) of the index condition population and, within the overview groupings, produce details on, for example, electronic frailty index, comorbidities, and coprescriptions. The disclosure control mechanism is integral to the tool, limiting tabular counts to meet local governance needs. An exemplary result for gout as an index condition is presented to demonstrate the tool’s functionality. Guideline developers from the National Institute for Health and Care Excellence and the Scottish Intercollegiate Guidelines Network provided positive feedback on the tool. Conclusions The tool is a proof-of-concept, and the user feedback has demonstrated that this is a step toward computer-interpretable guideline development. Using the digital tool can potentially improve evidence-driven guideline development through the availability of real-world data in real time.

Intermediate risk prostate tumors contain lethal subtypes

In 2024, prostate cancer (PCa) remains the most common non-skin cancer in males within the United States, with an estimated 299,010 new cases, the highest increase incident trend rate (3.8%) of all cancers, and one of the eight deadliest. PCa cases are projected to double from 1.8 million to 2.9 million per year between 2020 and 2040. According to the National Comprehensive Cancer Network (NCCN) treatment guidelines, most cases (65%) are intermediate risk (Gleason sum score <7 [3 + 4, 4 + 3], prostate organ-confined, and PSA < 20) with treatment options limited to active surveillance, external beam radiation, and/or surgery to prevent metastasis in the long term (>10 years). It is increasingly recognized that the two most common subtypes of intermediate risk PCa are cribriform architecture (CA) and intraductal carcinoma of the prostate (IDC-P), which can occur together, and both are associated with increased metastatic risk, biochemical recurrence, and disease-specific mortality. Both subtypes display hypoxia, genomic instability, and are identified as Gleason 4 in pathology reports. However, since false negatives are common (up to 50%) in these subtypes on biopsy, more research is needed to reliably detect these subtypes that have an increased risk for invasive disease. We note that even with mpMRI-guided biopsies, the sensitivity is 54% for cribriform architecture and only 37% for IDC-P. The presence of these PCa subtypes in biopsy or radical prostatectomy (RP) tissue can exclude patients from active surveillance and from designation as intermediate risk disease, further underscoring the need for increased molecular understanding of these subtypes for diagnostic purposes. Understanding the heterogeneity of intermediate risk primary PCa phenotypes, using computational pathology approaches to evaluate the fixed biopsy specimen, or video microscopy of the surgical specimen with AI-driven analysis is now achievable. New research associating the resulting phenotypes with the different therapeutic choices and vulnerabilities will likely prevent extracapsular extension, the definition of high-risk disease, and upstaging of the final pathologic stage.

Proposed biological definitions of Parkinson's disease confuse understanding without delivering meaningful advances

This article reflects on two proposals to classify and stage Parkinson's disease (PD) and related conditions based on the presence of aggregated alpha-synuclein (ASN) detected by alpha-synuclein aggregation assay (SAA). The authors highlight the significant shortcomings of the proposals: detection of ASN by SAA is not specific of PD or other well-established clinical conditions; they do not allow prediction of clinical course and prognosis; and they are not suitable as an endpoint for clinical trials. To move forward with proposals reflecting so many uncertainties and unknowns will just sow confusion and misunderstanding within the PD community.

Global Trends in Melanoma Burden: A Comprehensive Analysis from the Global Burden of Disease Study, 1990-2021

Melanoma, a significant global health concern, has shown evolving epidemiologic trends. Accurate estimation of melanoma's burden is essential for public health strategies and interventions. This study aims to estimate the incidence, mortality, and disability-adjusted life years for melanoma, stratified by region, gender, and age group, from 1990 to 2021. Using data from the Global Burden of Disease 2021, we analyzed melanoma incidence, mortality rates, and disability-adjusted life years in 204 countries from 1990 to 2021. These metrics were age-standardized and stratified by age, sex, Socio-Demographic Index, region, and country. The estimated annual percentage change was calculated to track temporal trends. Our study shows a substantial global increase in melanoma incidence, with significant disparities between genders and age groups. Higher Socio-Demographic Index regions had increased incidence rates, while global mortality declined, likely due to improved detection and treatment. The reliance on estimates and models may introduce bias due to variability in disease definitions, diagnostic criteria, and data collection methods. This study underscores the dynamic nature of melanoma's burden and the need for targeted, age-specific, and gender-specific interventions. Continued research is essential to address the growing challenges posed by melanoma.

Evaluating case definitions of respiratory disease in dairy calves: a scoping review.

Evaluating case definitions of respiratory disease in dairy calves: a scoping review.

FROM GUIDELINES TO MISSED OPPORTUNITIES: A CRITICAL ANALYSIS OF ANCA VASCULITIS MANAGEMENT PRACTICES

Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) represents a collection of rare autoimmune disorders that primarily target small blood vessels. This group includes granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), and microscopic polyangiitis (MPA). The diagnosis of AAV is multifaceted, relying on a combination of clinical assessments, biological markers, radiological imaging, and histopathological evaluations.Although the revised Chapel Hill classification has refined disease definitions, the absence of ANCAs in some patients can complicate diagnosis. The management of AAV typically begins with an induction phase aimed at inducing remission. This phase often incorporates corticosteroids (CS) or Avacopan in conjunction with immunosuppressants such as Rituximab (RTX) or Cyclophosphamide (CYC). Following this initial treatment, patients generally transition to maintenance therapy. Despite significant advancements in the understanding and treatment of AAV, challenges persist regarding accurate prognosis and therapeutic management. To evaluate disease severity and inform treatment decisions, clinicians utilize tools such as the Five-Factor Score (FFS) and the Birmingham Vasculitis Activity Score (BVAS). However, these assessment instruments have inherent limitations and may not fully encapsulate the complexity of the disease. Recent epidemiological research has underscored geographic variability in the incidence of AAV and highlighted the role of ANCAs as crucial diagnostic and prognostic markers.Evaluating long-term sequelae using indices such as the Vasculitis Damage Index (VDI) is essential, especially given improved survival rates and an increasing focus on enhancing patients quality of life.Current treatment strategies aim to minimize relapses and manage complications, including infections and metabolic disturbances however, there is a pressing need for more personalized approaches.This review emphasizes the importance of developing more sophisticated prognostic tools and activity scores to improve clinical management of AAV. It also advocates for continued research to optimize treatment strategies and enhance outcomes for patients affected by these challenging conditions.

Differences between hepatocellular carcinoma caused by alcohol and other aetiologies.

Alcohol-related liver disease is the third cause of hepatocellular carcinoma worldwide and the leading cause in Europe. Additionally, the recent definition of Metabolic dysfunction-Associated Steatotic Liver Disease with increased alcoholic intake will enrich this population with a more nuanced phenotype, reflecting recent epidemiological trends. In these patients, hepatocellular carcinoma diagnosis is often delayed and less frequently detected through screening programs. Moreover, at the time of diagnosis, patients with alcohol-related hepatocellular carcinoma tend to have a poorer general condition, more severely impaired liver function, and a higher prevalence of comorbidities, leading to increased competitive mortality. However, when hepatocellular carcinoma is diagnosed during surveillance programs in patients with alcohol-related liver disease or metabolic dysfunction-Associated steatotic liver disease with increased alcoholic intake, the rate of allocation to first-line curative treatments is high (56%) and comparable to that of patients with virus-related hepatocellular carcinoma. As a consequence, the etiology of the underlying cirrhosis cannot be considered an independent prognostic factor in patients with hepatocellular carcinoma. Instead, prognosis is driven by liver function, general condition, and tumor burden. This underscores the crucial role of early diagnosis through periodic surveillance in patients with Alcohol-related liver disease or Metabolic dysfunction-Associated Steatotic Liver Disease with increased alcoholic intake -related cirrhosis.

Is a Consensus Case Definition for Viral Associated Lower Respiratory Tract Disease (LRTD) in Clinical Trials Possible?

Lower respiratory tract illness or disease (LRTI/LRTD) represents a significant source of morbidity and mortality following viral respiratory illnesses, yet a consensus definition for this outcome is lacking. Recent studies of novel vaccines against respiratory syncytial virus (RSV) for older adults used LRTI/LRTD as the primary outcome to assess vaccine efficacy. However, the different vaccine trials have used highly variable criteria to define this outcome, leading to difficulty in comparison of vaccine efficacy results between trials. Here we review the key differences in criteria for case definitions, highlight strategies to best approximate compatibility between definitions, and review vaccine efficacy results among currently US Food and Drug Administration (FDA)-approved vaccines using these strategies. We hope this overview will support the need to develop a consensus definition for LRTI/LRTD to improve future research related to viral respiratory disease.

History of antineutrophil cytoplasmic autoantibodies : Milestones in rheumatology.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are autoimmune inflammatory small-vessel disorders with potentially life-threatening organ manifestations. Recent disease definitions and classification criteria allow distinction between granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), and non-granulomatous microscopic polyangiitis (MPA). The discovery of ANCA-autoantibodies directed against proteolytic enzymes of neutrophil granules-has enabled earlier diagnosis of AAV and paved the way to stage-adapted treatments. ANCA testing initially relied on different immunofluorescence patterns, i.e., cytoplasmic ANCA (C-ANCA) vs. perinuclear ANCA (P-ANCA), in ethanol-fixed neutrophils. This is nowadays outperformed by well-standardized immunoassays against the ANCA target antigens proteinase3 (PR3) and myeloperoxidase (MPO) for the diagnosis of small-vessel vasculitides. The discovery of ANCA has contributed substantially to unravelling the pathogenesis of AAV, which comprises neutrophil degranulation, NETosis with concurrently amplified ANCA antigen presentation, and intra- and transmural vascular inflammation involving the alternative complement system in susceptible individuals. There is agenetic disposition concerning certain HLA alleles and polymorphisms of the proteinase3 gene. Furthermore, epigenetic modifications impact on disease activity and relapse. During follow-up, the ANCA titer is not areliable mirror of disease activity; however, PR3-ANCA positivity is associated with agreater likelihood of relapse and abetter treatment response to rituximab as compared to cyclophosphamide/azathioprine. Within the past 60years, the discovery of ANCA has revolutionized the ability to diagnose, understand, classify, and treat AAV in atargeted manner.

SynNeurGe: The road ahead for a biological definition of Parkinson's disease

While significant progress has been made in treating Parkinson's disease (PD) symptoms, disease-modifying therapies (DMTs) have consistently failed. To address the underlying molecular mechanisms of PD, two biology-based criteria have been proposed: the “Synucleinopathy-Neurodegeneration-Genetics” (SynNeurGe) and “neuronal α-synuclein disease” (NSD) frameworks. Both frameworks emphasize the importance of biological markers over clinical symptoms. They recognize α-synuclein aggregation and genetic mutations (such as SNCA) as key diagnostic elements, with α-synuclein seed amplification assays (SAA) in cerebrospinal fluid (CSF) used to detect early disease stages. Dopaminergic neurodegeneration, measured by DAT imaging, is also central to both frameworks. These shared features aim to improve early diagnosis and precision medicine for PD. However, SynNeurGe provides a broader, more flexible framework that integrates α-synuclein pathology (S), neurodegeneration (N), and genetics (G), linked to clinical features (C). It aims to accommodate the complexity of PD and related Lewy body diseases, facilitating research on targeted DMTs. In contrast, NSD focuses specifically on PD and Lewy body dementia, introducing a staging system (NSD-ISS) based on biological markers and clinical impairment, helping track disease progression from preclinical to symptomatic stages. Despite their differences, both approaches highlight the need for more specific biomarkers and prospective studies to improve early intervention and personalized treatment. Harmonizing SynNeurGe and NSD concepts will be key in creating a universally accepted framework for precise PD diagnosis and therapy development.

Important Guide for Natural Compounds Inclusion in Precision Medicine

Precision medicine describes the definition of disease at a higher resolution by genomic and other technologies to enable more precise targeting of disease subgroups with new therapies. Preventative or therapeutic interventions can be developed with the knowledge of how a compound acts safely in the body to target receptors and produce the desirable effect. With the completion of the Human Genome Project in 2003 and the rapid increase in sequencing and bioinformatics tools, obtaining information about a person's genome is becoming more accessible. To make use of genetic information in precision or personalised medicine, it is important to examine the roles of natural remedies in the individualization of treatment - to use as the right drug, at the correct dose, for the right person, at the right time. Integrating biomarkers, especially within clinical workflows, plays a crucial role in implementing precision medicine. Though the horizon in precision medicine looks promising, one major issue resides in the precise mapping into clearly defined medical conditions associated with biomarker identification and precedence ranking. This communication is met to provide guidelines that could improve biomarker discovery and enhance the participation and integration of novel natural compounds in the processes of implementing precision or personalized medicine.

Long COVID across SARS‐CoV‐2 variants: Clinical features, pathogenesis, and future directions

AbstractLong coronavirus disease (COVID) is characterized by persistent symptoms following severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection and has emerged as a significant health concern. As SARS‐CoV‐2 evolved from the wild‐type strain to the Alpha, Beta, Delta, and Omicron variants, there may be a variant‐specific influence on long COVID akin to the acute disease. This review aims to summarize our current knowledge of variant‐specific influences in long COVID incidence, symptom profile as well as mechanisms of pathogenesis. We highlight that long COVID incidence may be lower with the Omicron variants. The symptom profile of long COVID may also show some dependence on the different variants, with a reduction in cardiopulmonary symptoms with more recent SARS‐CoV‐2 variants. This heterogeneity of long COVID may also be related to the variant‐specific differences in affecting the immune system, viral persistence, and autoimmunity. However, emerging data also suggest that vaccinations may play a big role in shaping the presentation of long COVID. We also highlight ongoing work on long COVID incidence and symptom profiles in populations infected only by the Omicron variants. This will be beneficial toward more useful disease definitions and the development of effective diagnostic and therapeutic strategies.

From clinical to biological definitions of neurological diseases.

From clinical to biological definitions of neurological diseases.

P004 Difficult to Treat axial Spondyloarthritis- insights from a tertiary rheumatology service

Abstract Background Therapy non-response (NR) can be seen in 30% of axial spondyloarthritis (axSpA) with some patients requiring multiple therapies. We wanted to assess in our axSpA population those with difficult to treat (D2T) disease as defined in two ways: (ever) failure of any 2 b/ts-DMARDs which we called “standard definition” or (ever) failure ≥2 b/ts-DMARDs with differing mechanisms of action (MoA), “strict definition”. Aims To describe the clinical, laboratory and imaging characteristics of axSpA patients meeting varying definitions of D2T disease and to compare differences between those responding to their current b/tsDMARD (BASDAI <4) and those who are not (BASDAI ≥4). Methods A cross-sectional analysis of b/ts-DMARD prescribing in the Leeds Specialist Spondyloarthritis Service identified patients with axSpA treated with a b/ts-DMARD between October 2023 and May 2024. Demographics and clinical characteristics including BASDAI, CRP and imaging were assessed. Patients were classified as NR at the time of assessment based if BASDAI ≥4, as a marker of ongoing disease activity. Results Overall, 680 patients on b/ts-DMARDs were identified, of which 109 (16.0%) had (ever) failed any 2 b/ts-DMARDs and 58 (8.5%) ≥2 b/ts-DMARDs with differing MoA. The demographics were similar between groups with mean age (49.2 [SD12.4] vs 49.5 [SD12.3]), predominant male sex (62% vs 65%), HLA-B27 (77% vs 81%), and prevalence of radiographic disease (59% vs 56%) in those meeting standard and strict definitions respectively. At last clinical review, 99 (91%) patients meeting standard definition and 51 (88%) meeting strict definition remained on a b/ts-DMARD. Of the patients reviewed during 2023/2024, 40/55 (73%) meeting the standard definition and 18/25 (72%) meeting the strict definition had NR. In patients experiencing NR, 17/35 (49%) had CRP >5 mg/L in the standard definition compared to 7/15 (47%) in the strict definition. Active inflammation on MRI was found on 1/4 patients meeting the standard criteria and 0/2 patients meeting the strict criteria. All patients had non-axSpA related pathology on MRI. Conclusions In this cross-sectional assessment a small proportion of axSpA patients appear to have D2T disease according to above definitions. Objective evidence of inflammation was seen in less than 50% either by CRP, MRI or both, suggesting a mix of non-inflammatory and true refractory disease. Further characterization of these populations in this and larger cohorts may identify predictors of non-response to b/tsDMARD therapy in axSpA.

Validation and Epidemiologic Definition of the Novel Steatotic Liver Disease Nomenclature in a National United States Cohort With Cirrhosis.

Novel steatotic liver disease (SLD) definitions were introduced in 2023. Accurate and meaningful classifications using clinical data are needed to study interventions and outcomes. In a national cohort of Veterans with cirrhosis and imaging-confirmed steatosis, 7 algorithms differentially emphasizing cardiometabolic risk factors (CMRFs) and alcohol exposure were developed to define alcohol-associated liver disease (ALD), metabolic dysfunction associated SLD (MASLD), and MASLD with increased alcohol intake (MetALD). The primary outcome was classification of SLD, which was validated using hospitalizations for major acute cardiac events (MACE) and alcohol use disorder (AUD). Secondary outcomes included longitudinal Child-Turcotte-Pugh class, incident hepatocellular carcinoma, and all-cause mortality. In all, 31,514 patients with cirrhosis (median age 64 years) were included. CMRFs (98.8% ≥ 1) and hazardous alcohol use (65.3%) were highly prevalent. The distributions of MASLD, MetALD, and ALD varied substantially across classification methods with varying CMRF and alcohol criteria. For example, MetALD ranged from 4.7% to 47.2%. Using method 4, incidence rates of MACE hospitalizations in MASLD, MetALD, and ALD were 16.7, 14.5, and 8.4 per 100 person-years, respectively, and incidence rates of AUD hospitalizations were 2.0, 26.1, and 47.6 per 100 person-years, respectively. Hypertriglyceridemia and low high-density lipoprotein were common across SLD subtypes, including ALD (67.3% hypertriglyceridemia; 48.2% low high-density lipoprotein). Patients with ALD (hazard ratio, 1.41; 95% confidence interval, 1.34-1.48) had significantly higher hazards of mortality relative to MASLD. Classification of SLD is highly sensitive to relative weighting of CMRFs and alcohol use. Clinically relevant definitions should consider data availability on alcohol and the limitations of lipid measurements in distinguishing SLD subtypes.

Where the Genetic Code Meets the Zip Code: Advancing Equity in Rare Disease Genomics.

The promise of genomic medicine lies in the opportunity to improve health outcomes via a personalized approach to management, grounded in genetic and genomic variation unique to an individual. However, disparities and inequities mar this remarkable landscape of genomic innovation. Prior efforts to understand these inequities have focused on populations for which genetic testing is relatively protocolized or where test utility varies greatly by ancestry groups, where equitable outcomes are more clearly defined. We therefore consider the current landscape of rare disease genomics, in which diagnostic approaches vary widely and utility remains to be fully understood, and suggest a path forward: how ecosocial theory may be used to guide novel equity-focused initiatives that incorporate illness narratives to improve population health. We present examples of narrative medicine in rare disease and reimagine the role this discipline may play in genomic sequencing studies, toward incorporation of the unique illness narrative into clinical genetics and genomics practice. Approaches that broaden the definitions of disease and of outcomes of interest will force the field to grapple with its racist history and begin to advance health equity and promote justice so that genomic medicine may truly deliver on its promise.

Classification and epidemiologic analysis of 86 diseases in China's Second List of Rare Diseases.

Following the release of China's First List of Rare Diseases in May 2018, the Chinese government officially published China's Second List of Rare Diseases in September 2023. To date, there is no unified standard and international consensus for rare diseases, and epidemiologic data for most rare diseases in China are lacking. We investigated 86 rare diseases on the second list using Orphanet and other databases to clarify the classification, nomenclature, and epidemiologic data for these diseases, and we summarized the genotype and phenotype of hereditary diseases. The results showed that most of 86 rare diseases were coded in the database of Unified Medical Language System (UMLS), Orphanet, Medical Subject Headings (MeSH) and International Classification of Diseases, Eleventh Revision (ICD-11). Some rare diseases are composed by group of different disorders, in which multiple identifiers existed. Meanwhile, some rare diseases have different subtypes, which correspond to different identifiers. This increases the actual number of rare diseases in the second list. Over 50% of rare diseases are genetic rare diseases and they are mainly classified into neoplastic diseases, transplant-related disorders and neurological diseases. Epidemiologic data indicated that these rare diseases had a broad prevalence spectrum and over 20 rare diseases had a prevalence of over 1/10,000, these rare diseases in the China's Second List of Rare Diseases expanded the number and scope of rare diseases according to the China's official definition of rare diseases.

Aspartate aminotransferase-to-platelet ratio index outperforms Fibrosis-4 in 2843 Korean patients with metabolic dysfunction-associated steatotic liver disease.

The definition of metabolic dysfunction-associated steatotic liver disease (MASLD) has recently been proposed. We aim to investigate the diagnostic efficacy of noninvasive fibrosis markers in predicting liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD), metabolic dysfunction-associated fatty liver disease (MAFLD), and MASLD. This retrospective study involved 2843 patients diagnosed with steatotic liver disease at six tertiary hospitals in South Korea. Liver fibrosis was assessed using vibration-controlled transient elastography, and various noninvasive markers, including the aspartate aminotransferase-to-platelet ratio index (APRI), Fibrosis-4 index (FIB-4), NAFLD fibrosis score (NFS), and serum Mac-2-binding protein glycosylation isomer were analyzed. Among 1106 patients, 79.9% met criteria for NAFLD, MAFLD, and MASLD. The APRI had area under the receiver operating characteristic curve (AUC) values of 0.819, 0.821, and 0.818 for liver fibrosis≥F2, and 0.819, 0.824, and 0.884 for liver fibrosis≥F3, and 0.890, 0.884, and 0.889 for fibrosis≥F4 in NAFLD, MAFLD, and MASLD, respectively. The FIB-4 index showed AUC values of 0.776, 0.793, and 0.778 for fibrosis≥F2, 0.788, 0.814, and 0.79 for fibrosis≥F3, and 0.846, 0.859, and 0.856 for fibrosis≥F4. The APRI consistently had the highest AUC values, except in individuals older than 64years for fibrosis≥F4. The APRI was the most effective noninvasive fibrosis marker across NAFLD, MAFLD, and MASLD, particularly in age-stratified analyses. Further research is needed to establish standardized cut-off values and enhance the clinical utility of these markers in managing liver fibrosis.

Peningkatan Pengetahuan Perawat Tentang Pemberian Obat DOTS pada Pasien TB di RSU IPI Medan

TB is one of the 10 causes of death and the primary cause of infectious agents in the world. The prevalence of tuberculosis patients in 2020 amounted to 929 patients. Some of the influencing factors are behavioral factors, namely knowledge, attitude and behavior in the implementation of routine medication compliance. The method used was observational descriptive with 30 participants who were residents of Sampali Village, Percut Sei Tuan District. The PkM team provided the material in question: 1) Definition of tuberculosis disease, 2) Causes of tuberculosis disease, 3) Signs and symptoms of tuberculosis disease, 4) Complications of tuberculosis disease, and 5) Prevention of tuberculosis disease. After the implementation of the activity: 1) The majority of the understanding of tuberculosis (TB) is good as many as 25 people, 2) The causes of tuberculosis (TB) are mostly good as many as 27 people, 3) The signs and symptoms of tuberculosis (TB) are mostly good as many as 26 people, 4) The majority of tuberculosis (TB) complications are good as many as 27 people, and 5) Prevention of correct transmission of tuberculosis (TB) all participants have been able to as many as 27 people. The increase in knowledge and skills of participants is because the community has a great desire to treat and prevent dengue fever in family members at home.

Serum free light chains in a racially diverse population including African Americans and populations from South Africa

Detection of light chain (LC) monoclonal gammopathies (MG) traditionally relies on serum free LC (FLC) κ, λ, and their ratio (κ/λ) reference ranges based on a mostly White population. We investigated FLC values in a racially diverse population by screening 10,035 individuals for heavy chain MG, identifying 9,028 negative cases whose FLC were measured. Participants included 4,149 from the PROMISE Study (US, n=2,383; South Africa, n=1,766) and 4,879 from the Mass General Brigham Biobank, with 44% self-identifying as Black. Using standard FLC reference ranges, 1,074 out of 10,035 individuals (10.7%) were diagnosed with LC-MGUS, with 99% being κ-restricted. In the US, 14.8% of Black and 4% of White individuals were diagnosed (p<0.01). Among US participants of African (AFR) and European (EUR) genetic ancestry, 14.4% AFR and 2.9% EUR were diagnosed (p<0.01). Among South Africans (100% Black), 27.8% were diagnosed using standard ranges. To avoid overdiagnosis, we propose a new κ/λ ratio reference range (0.686 to 2.10) for populations of African descent with normal renal function, with standard values for κ and λ being 7.97 to 77.50 mg/L and 6.20 to 49.20 mg/L, respectively. This reduces LC-MGUS overdiagnosis by 91% (10.7% vs. 0.97%). Using the new reference, LC-MGUS accounts for 8.8% of MGUS cases, with 74% being κ-restricted, consistent with LC myeloma rates. These findings highlight the importance of basing disease definitions, such as MGUS, on diverse populations. Adopting our proposed FLC reference values would reduce MGUS overdiagnosis among Black individuals, avoiding unnecessary financial, psychological, and medical consequences.