Screening Of At-risk Individuals Research Articles

Celiac disease - a review on recent advances in characteristics, diagnostic and treatments

Introduction and purpose:
 Celiac disease occurs in 1% of the general population. However, many cases remain unrecognized.
 The disease is a chronic immune-mediated disorder triggered by the ingestion of gluten that appears in individuals with genetic susceptibility. Celiac disease can develop in paediatric patients as well as adults.
 The purpose of this review is to analyze the newest information on the characteristics, diagnosis and treatment of patients with celiac disease. 
 Material and methods:
 This review was based on available data collected in the PubMed database and published between 2015 and 2022. The research was done by looking through keywords such as: “celiac disease”, “Gluten-Free Diet”, “diagnosis” and “treatment”.
 Results:
 The diagnosis of celiac disease is most often delayed due to the broad spectrum of presentations. Screening of at-risk individuals is important to progress the diagnosis.
 It is additionally crucial to raise clinicians' attention to non-specific parenteral symptoms that may indicate celiac disease. The majority of the symptoms arise from nutritional deficiencies caused by intestinal malabsorption. According to scientific reports, the most common deficiencies of people with celiac disease are iron, folic acid, vitamin B12, fat-soluble vitamins and a calcium.
 Conclusions:
 Recent years have seen the emergence of research into new therapeutic options, but their efficacy and safety still need to be evaluated more thoroughly. Strict adherence to a gluten-free diet by patients is still the only treatment option at present.
 Celiac disease, due to the constant increase in knowledge about its pathogenesis, diagnosis and treatment is an important material for further research.

Exploration of identifying novel serum biomarkers for malignant mesothelioma using iTRAQ combined with 2D-LC-MS/MS

Malignant mesothelioma (MM) is an aggressive cancer linked to asbestos exposure. Its poor prognosis makes early diagnosis extremely important, which would provide an opportunity for early treatment and potentially changing outcomes. This study aimed to explore the underlying mechanisms of MM and discover novel noninvasive biomarkers for the diagnosis of malignant mesothelioma. Using Isobaric tags for relative and absolute quantitation (iTRAQ) combined with two-dimensional liquid chromatography/tandem mass spectrometry (2D LC-MS/MS), a total of 145 differentially expressed serum proteins were identified between MM patients and healthy controls. The identified proteins were further analyzed by bioinformatics, out of which three candidate biomarkers (Filamin A (FLNA), Fibulin 1 (FBLN1) and Thrombospondin-1 (TSP-1)) were validated in large cohorts of patients with asbestos-related diseases including MM patients by ELISA assay. Receiver operating characteristic (ROC) curve analysis showed that serum FLNA, FBLN1 and TSP-1 had high diagnostic values in distinguishing MM patients from healthy controls, individuals with asbestos exposure (AE), and patients with pleural plaques (PP) or asbestosis. Meanwhile, serum FBLN1 and TSP-1 possessed good diagnostic values in distinguishing asbestosis patients from healthy controls and individuals with AE. The combination of FLNA, FBLN1, and TSP-1 proteins had higher sensitivity and specificity in discriminating patients with MM, PP and asbestosis. Our findings indicated that analysis of serum proteome using iTRAQ is a feasible strategy for biomarker discovery, and serum FLNA, FBLN1 and TSP-1 may be promising candidates for diagnosis of malignant mesothelioma and screening of at-risk individuals.

Sustainability of a Tuberculosis Screening Program at an Adult Education Center Through Community-Based Participatory Research.

The majority of active tuberculosis (TB) cases in the United States occur through reactivation of latent TB infection among foreign-born individuals. While screening of at-risk individuals through community partnerships is recommended, it is not commonly accomplished. A community-academic partnership developed a TB-screening intervention at an adult education center serving a large foreign-born population in Rochester, Minnesota. The intervention was cocreated with grant support by diverse stakeholders through a community-based participatory research partnership. The intervention was sustained beyond the grant interval through adaptation of staffing inputs, a robust partnership with sustained dialogue around TB and operational issues, and adaptation of governance through coownership of the intervention by the adult education center and the public health department. Eight years of data demonstrate that adult education centers may be effective venues for sustaining partnerships to address TB prevention among at-risk communities.

Quality improvement of lung cancer patient selection using clinic-based spirometry.

282 Background: Coordinating lung cancer screening requires risk assessment for patient selection. Optimal selection can reduce costs and improve efficiency of low dose computed tomography (LDCT) screening of lung cancer. This study evaluated clinic-based spirometry as a tool to improve patient selection for lung cancer screening. Methods: Eligibility criteria for three large LDCT screening studies were retrospectively applied to the highest risk patients enrolled in the Princess Margaret Lung Cancer Screening Program who had received clinic-based research spirometry. The three studies were: Danish Lung Cancer Screening Trial (DLST), National Lung Screening Trial (NLST), and the Ontario Lung Cancer Screening Program (OLCS). Lung cancer incidence was compared between those who would were included by the screening study eligibility criteria (Group I), those who were excluded by the eligibility criteria but demonstrated obstruction on spirometry (defined as a Forced Expiratory Volume in 1 Second % Predicted (FEV1%) < 90%) (Group II), and those who did not meet eligibility criteria and had no obstruction (FEV1% ≥90) (Group III). Results: The 321 highest risk participants of the screening program had a mean age of 65 years and were 39% male. The median number of pack years in this group was 39. After undergoing spirometry, this cohort was screened using LDCT for a median of 3.3 years (range 1–8.1 years). Under DLST criteria, Groups I and II had virtually identical lung cancer incidences detected by screening at 13.1% and 13.6% of the individuals screened, respectively; Group III had a substantially lower incidence at 6.3%. Results were similar by NLST criteria where the incidence of screen-detected lung cancer were 13.7% for Groups I, 11.1% for Group II, and 8.6% for Group III. Under OLCS criteria, these values were 13.4% (Group I), 13.5% (Group II), and 8.2% (Group III). Conclusions: Individuals who were excluded from LDCT screening because they lacked other clinical eligibility criteria, but had a FEV1 < 90%, had similar lung cancer incidence as patients who had met screening study eligibility criteria. Coordinating care for screening of at-risk individuals could be improved by incorporating spirometric tools.

Quality improvement pilot to engage rural Kentucky frontline against lung cancer death.

164 Background: Kentucky is the epicenter of smoking and lung cancer in the U.S.: over half the population is a current or former smoker (second only to WV); and it has the highest annual lung cancer incidence—89.6 per 100,000 population—according to the most recent CDC data. While offering a significant, double-digit death benefit due to early recognition and improved therapies, LDCT lung cancer screening of at-risk individuals remains extremely low. Helping primary care practices identify their at-risk patients, promote reduced tobacco use, and refer for screening is critical. Methods: In this pilot, family practice and internal medicine practices, residency programs, and federally qualified health centers (FQHCs) were recruited in rural regions of Eastern Kentucky with populations at highest risk. The Sustainable Healthy Communities Quality Improvement Education (SHC-QIE) model—which engages multidisciplinary practice leaders, rapid cycle improvement or a PDSA approach to QI, geoanalytics, and community engagement support—was implemented to promote better screening while enhancing clinician satisfaction. Results: Each practice significantly improved their identification of smokers and patients qualifying for lung cancer screening in the Medicare program as well as screening referrals by nearly 2-fold. For example, in one FQHC, accurate reporting of tobacco history data in the medical record increased from 34.6% to 56.9%. Another example showed referrals for LDCTs increased from 230 in 2017 to 412 in 2018, with a 71% increase over baseline. While survey data from the participating clinics conceded challenges in implementing a QI initiative, significant satisfaction with the initiative, ongoing plans for activities building on the program, and community engagement were found as well. Pre-, post-survey data also revealed significant improvement in screening, tobacco counseling, and LDCT referral. Conclusions: In spite of EMR barriers, significant increases in smoking history taking, counseling for tobacco cessation, and referral for lung cancer screening was achieved over the course of 9 months.

SAT-333 Genetic studies of inherited kidney diseases causing chronic kidney disease

The genetic investigation of inherited ciliopathies and cystic kidney disease is crucial as it provides valuable diagnostic information and allows screening of at-risk individuals and genetic counseling to be undertaken. The continuous growing of the number of disease causative genes is making-routine clinical diagnosis through next-generation sequencing technologies is consistent in routine clinical diagnosis. A comprehensive diagnosis panel targeting 49 genes associated with cystic kidney disease and ciliopathy syndromes were designed and validated using Agilent SureDesign tool. The captured and indexed libraries were prepared using HaloPlex HS Target Enrichment System and sequenced as a multiplex of 12 samples on an IlluminaMiSeq sequencer in 250 bp paired-end mode. The panel was efficient and specific at covering the candidate genes and providing rapid and accurate genetic diagnosis. Moreover, it was sensitive at detecting different types of mutations including missense, nonsense, small INDELS and whole gene deletion. A total of 11 unreported pathogenic mutations suspected as the causative genetic aetiology were detected by the NGS in the PKD1, PKHD1, SDCCAG8, WDR19, NPHP1, NPHP3 and NPHP4genes. All suspected pathogenic mutations were validated by Sanger sequence. Overall, using this customized targeted NGS resulted in a comprehensive molecular genetics diagnosis in 34/45 patients (75.6%). Tabled 1Cystic kidney diseases and the associated genes included in the panelDisease GroupDisease NameOMIM No.MOICharacteristic fearturesGene symbol(s)Cystic CiliopathiesADPKD (Type 1 & 2)#601313, #173910ADpolycystic kidneys, liver cysts, brain aneurysms, CKDPKD1, PKD2ARPKD#263200ARpolycystic kidneys, liver fibrosis, CKDPKHD1Nephronophthisis types 1-9#256100ARpolyuria, polydipsia, anemia, CKDNPHP1-NPHP9Medullary cystic kidney disease#174000ADAdult onset CKD, hyperuricemiaUMOD, MUC1Meckel-Gruber syndrome (MKS)#249000 #607361ARPolycystic kidneys, multiple organ dysplasia, perinatal lethalMKS1, MKKS, CC2D2ABardet-Biedl syndrome types 1–12#209900ARRetinitis pigmentosa, polydactyly, MR, hypogenitalism and obesity, rarely cause CKDBBS1-BBS12, ARL6Polycystic liver disease#174050ADMultiple fluid-filled cysts throughout the liver, cysts of biliary epithelial origin, renal cysts, few (in some patients)PRKCSH, SEC63Renal cysts and diabetes syndrome# 137920ADcongenital anomalies of the kidney and urinary tract (CAKUT), chronic renal failure, structural kidney abnormalities, unilateral kidney agenesis, renal cystsHNF1BOther cystic kidney disease#601331,ADRenal dysplasiaBICC1#213300ARJoubert syndromeAHI1, CEP290, TMEM67, TTC21B, RPGRIP1L# 267430ARRenal tubular dysgenesisREN Open table in a new tab Tabled 1Clinical diagnosisMean age (Y/M) (range)M/FTotalGenetic etiologyNo genetic etiologyPercentage of GeneticADPKD40.2 (7 -55 Y)7/61311285%ARPKD9.2 (2M -28Y)6/1016160100%Nephronophthisis (NPHP)6.3 (0- 13Y)2/8116555%Meckel Gruber syndrome5.3 (3-10M)2/131233%Joubert syndrome1/01010%BBS1/01010% Open table in a new tab The high diagnostic yield and accuracy of this comprehensive targeted gene panel validate the use of broad NGS-based testing for patients with suspected inherited kidney disease.

Personality Style in Behavioural Disturbances in Parkinson?s Disease

Objective: Non-motor changes in Parkinson’s disease (PD) can include behavioural disturbances, such as apathy and impulse control disorders (ICDs). These behavioural problems impact on quality of life and carer burden. In the case of impulsivity, there is some association with specific personality styles at the time of assessment. This study compares current and pre-morbid personality attributes among people with PD who experience a clinically significant ICD, apathy, or no behavioural disturbance. Methods: 94 PD participants without dementia (ICD, n=34; apathy, n=24; control, n=36) were examined for current and pre-morbid (10 years before PD onset) personality style using self- and informant- versions of the NEO Five-Factor Inventory. All informants were knowledgeable about patients’ midlife personalities and provided both current and pre-morbid ratings. Results: When key co-variates (depression, anxiety, age and dopamine load) were controlled for, a difference in self-reported current personality style was found among the three PD groups, with the ICD group rating themselves as less agreeable compared to those with apathy or no behavioural disorder. Informant-rated current and pre-morbid measurements of personality style did not differ. Conclusion: While PD patients with clinically significant ICDs currently report themselves as being less agreeable, their informants did not support this finding and reported no change from pre-morbid personality. Differences in personality style with impulsive-compulsive behaviours in PD may not be discernable to others and may be related to transient ‘state’ factors (i.e. influenced by the disease process or response to treatment), rather than the more enduring trait characteristics exhibited prior to the onset of PD. Until longitudinal investigation of personality determinants has been conducted, there should be a cautious approach in screening for at-risk individuals using specific personality attributes, to avoid overlooking persons with PD who may be vulnerable to developing behavioural complications.

Presymptomatic diagnosis using a deletion of a single codon in families with hereditary non-polyposis colorectal cancer

The diagnosis of hereditary non-polyposis colorectal cancer (HNPCC) is often confirmed by a mutation in one of several mismatch-repair genes, in particular MLH1, MSH2 and MSH6. Presymptomatic diagnosis requires the identification of a mutation causing the disease. Three different deletions of a single amino acid codon have previously been published as assumed pathogenic. The objective of this study was to determine if an MSH2 3 base pair in-frame deletion (N596del) could be used in presymptomatic screening of at-risk individuals. We report on five HNPCC families with the N596del mutation, identified after mutation screening of MSH2 and MLH1. All patients in the families were haplotyped using markers flanking the MSH2 gene. The haplotypes revealed that the five families with high probability descended from only two founders. The N596del segregated with the HNPCC phenotype with lod scores of 3.2 and 2.0 at the recombination fraction of 0.0 in the two founder families. Sequencing of MSH2 and MLH1 did not reveal other pathogenic mutations, and N596del was not identified in 50 healthy controls. The mutation has previously been found expressed in mRNA, and is located in a conserved domain. The results support the hypothesis that N596del is the disease causing mutation and not a clinically silent variation. On this basis, the application of the MSH2 N596del mutation, in presymptomatic screening of HNPCC families, is recommended.

Glucocorticoid-remediable aldosteronism

Glucocorticoid-remediable aldosteronism (GRA) is a monogenic form of human hypertension that predisposes to cerebral hemorrhage. As a result of a chimeric gene duplication, aldosterone is ectopically synthesized in the cortisol-secreting zona fasciculata of the adrenal gland under the control of adrenocorticotropin (ACTH). Hypertension frequently has its onset during childhood and is usually refractory to standard anti-hypertensives such as ACE inhibitors and beta-blockers. Hypokalemia can develop in those treated with a potassium-wasting diuretic, but random potassium levels are usually normal. Diagnosis has been facilitated by the availability of a genetic test. Suppression of ACTH release with exogenous dexamethasone is a useful diagnostic and therapeutic strategy. Treatment with the mineralocorticoid receptor antagonists spironolactone and epleronone is also efficacious. The diagnosis of GRA facilitates directed therapies and screening of at-risk individuals and kindreds.

Basal cell carcinoma: update on management

SummarySkin cancer represents a significant health problem in the white adult population. Nurses have a responsibility in health promotion and disease prevention for patients at risk of developing the most common form of skin cancer, the basal cell carcinoma (BCC).BCC is managed using a combination of primary and secondary disease prevention strategies. These are education and screening of at-risk individuals in the community. Self-screening within the home, as well as opportunistic screening by health professionals, is deemed the most cost-effective strategy in the UK. Nurses, therefore, have a responsibility to educate patients about sun awareness, sun protection and early recognition of cancerous or pre-cancerous lesions. A number of treatment options are available for basal cell carcinoma with the decision to treat based on clinical appearance, histological examination, previous medical history and patient choice. Nurse, through the use of patient group directions and prescribing, can help to ensure the most appropriate treatment for individual patients.

Fifty years of the double helix and its impact on psychiatry

Objective: To discuss the impact of Watson and Crick's double helix discovery on the field of psychiatry. Method: Psychiatric research studies using molecular genetic techniques are summarized. The implications of these findings in terms of our understanding and treatment of mental illness are discussed. Results: There now exists growing evidence of candidate gene sites for a variety of psychiatric disorders ranging from schizophrenia to reading disability. Conclusions: The field of psychiatric genetics has become one of the most vital and productive areas of psychiatric research. New findings are continually coming to light, bringing us ever closer to understanding these complex disorders at a molecular level. Such knowledge could lead to improved drug treatments, screening of at-risk individuals and even a reduction in the stigma attached to psychiatric disorders.

Fifty years of the double helix and its impact on psychiatry.

To discuss the impact of Watson and Crick's double helix discovery on the field of psychiatry. Psychiatric research studies using molecular genetic techniques are summarized. The implications of these findings in terms of our understanding and treatment of mental illness are discussed. There now exists growing evidence of candidate gene sites for a variety of psychiatric disorders ranging from schizophrenia to reading disability. The field of psychiatric genetics has become one of the most vital and productive areas of psychiatric research. New findings are continually coming to light, bringing us ever closer to understanding these complex disorders at a molecular level. Such knowledge could lead to improved drug treatments, screening of at-risk individuals and even a reduction in the stigma attached to psychiatric disorders.

The association of an HPV16 oncogene variant with HLA-B7 has implications for vaccine design in cervical cancer

HLA-restricted cytotoxic T-lymphocyte (CTL) recognition of human papillomavirus (HPV) oncogene products may be important in the control of the HPV infections associated with the development of cervical cancer. We have identified, in HLA-B7 individuals, a consistent variation in the HPV16 E6 oncoprotein sequence, which alters an HLA-B7 peptide binding epitope in a way likely to influence immune recognition by CTLs. These results illustrate a biologically relevant mechanism for escape from immune surveillance of HPV16 in HLA-B7 individuals. Thus, both HLA type and HPV16 strain variation need to be considered in the screening of at-risk individuals and for the rational design of anti-HPV vaccines.

Reliability of a digital electroneurometer for the determination of motor latency of the median nerve

Measurement of distal motor latencies of the median nerve are often part of electrodiagnostic studies used to verify a diagnosis of peripheral neuropathy. Since electrodiagnostic studies are time consuming, expensive, and impractical for large-scale screening of at-risk individuals, a portable digital electroneurometer was developed for measuring motor latencies as a screening tool for early detection of nerve compression syndromes, including carpal tunnel syndrome. The purpose of this study was to determine the intertester and intratester reliability of a digital electroneurometer in subjects with (n=12) and without (n=20) clinical signs of carpal tunnel syndrome. This study addressed only the reliability and not the validity of this device. Using a repeated measures design, three evaluators performed two distal motor latency tests on the median nerve of each of the subjects. Pearson product-moment correlations for intratester reliability ranged from 0.94 to 0.99, and the intraclass correlation coefficient for intertester reliability was 0.96. Two examiners obtained statistically larger latency values on the second test, although these differences are judged to be clinically insignificant. Use of an electroneurometer may expand motor latency testing to a wider variety of settings.