Diagnostic Biomarkers: Are We Moving from Discovery to Clinical Application?

Despite considerable research investment, moving from biomarker discovery to clinical application has presented unique challenges. We aimed to evaluate progress toward clinical application of a sample of molecular- and “omics”-based diagnostic tests over a 10-year period. METHODS We used Scopus to locate studies, published before the December 31, 2016, citing 107 original-research articles published in 2006 that assessed the diagnostic value of a molecular- or “omics”-based test. We identified diagnostic studies of the same test and disease and determined whether the article represented progress in the validation of the molecular test. We classified the types of progress: (a) clinical validation (measuring diagnostic accuracy in a series of patients similar to the population in which the test will be used in practice), (b) technical improvement, (c) extended diagnostic application (modification of the diagnostic question attended initially by the test), (d) economic evaluation, or (e) clinical use or implementation. RESULTS In the 10-year period analyzed, 4257 articles cited the 107 diagnostic studies; 118 (2.8%) were diagnostic studies of the same test, and of these papers, 25 (21.2%) did not constitute progress toward validation of the test for use in clinical practice (potential research waste). Of the 107 molecular- or “omics”-based tests described in 2006, only 28 (26.2%) appeared to have made progress toward clinical application. Only 4 (9.1%) of 44 proteomics-based tests had made progress toward clinical application. CONCLUSIONS Articles evaluating molecular- or “omics”-based diagnostic tests are numerous in biomedical journals. Few tests have made progress toward clinical application in the 10 years following their discover

Untangling the association between prostatespecific antigen and diabetes: a systematic review and meta-analysis

Objectives Several studies have shown an inverse association between diabetes mellitus and prostate cancer (PCa). Some researchers suggest that this relationship is due to reduced PCa detection in diabetics due to lower prostate-specific antigen (PSA) levels compared to non-diabetics. Our objective is to analyze the impact of diabetes on PSA in asymptomatic men without known prostate pathology and without prior prostate intervention. Methods We searched Medline (via PubMed), Embase and Scopus. We included studies that reported the relationship between serum PSA levels and diabetes or diabetes treatment in asymptomatic adult men without known prostate pathology, and without prior prostate intervention. Pooled mean differences were compared between diabetics and non-diabetics. Results Of 2,392 screened abstracts, thirteen studies met the inclusion criteria and 8 (62%) reported appropriate measures that could be included in a meta-analysis. Eleven (85%) examined the influence of diabetes on PSA levels and 8 (62%) evaluated the influence of diabetes treatments on PSA levels. Overall diabetics had a significantly lower PSA level compared to non-diabetics (mean difference: −0.07 ng/mL; 95% CI −0.10, −0.04). Conclusions Diabetes and related factors (such as disease duration, severity and treatment) were significantly associated with lower PSA levels among asymptomatic men, yet differences were small and are unlikely to influence PCa detection in a screening setting

Addressing Health Disparities through Community Participation: A Scoping Review of Co-Creation in Public Health

Abstract: Background: There is general agreement regarding the relevance of community involvement in public health policy, practice, and research to reduce health inequities. Objective: This review aims to analyse the experiences of community engagement in public health actions, with particular attention to methodologies used and how community participation is articulated. Method and Analysis: We searched the Web of Science, EBSCO, and ProQuest for scientific articles published in peer-reviewed journals. We recorded methodological aspects, the approach to equity, actors that participated in the actions, and participation of the community in different phases (agenda setting, design, implementation, and evaluation). Results: Of 4331 records, we finally included 31 studies published between 1995 and 2021. Twelve studies referred to Community-Based Participatory Research as the framework used. The actions addressed equity, mainly by tackling economic vulnerability (n = 20, 64%) and racial discrimination (n = 18, 58%). Workshops were the most used method. Participation was frequently observed in the design and implementation phases of the action, but it was reduced to community feedback in the evaluation. Conclusions: Co-created public health actions offer the opportunity to reduce health inequity and promote social change; yet, further effort is needed to involve communities in the entire cycle of decision makin

Anemia and undernutrition in intestinally parasitized schoolchildren from Gakenke district, Northern Province of Rwanda

Background: Rwanda is a sub-Saharan country, where intestinal parasite infections, anemia and undernutrition coexist. The purpose of this research is to study the relationship between intestinal parasite infections and undernutrition/anemia to clarify the priorities of intervention in the rural area of Gakenke district in the Northern Province of Rwanda. Materials and methods: A total of 674 students from Nemba I School, participated in a cross-sectional study, in which their parasitological and nutritional status were analysed. Statistical analysis was performed by χ2 test, univariate analysis and Odds ratios (OR). Results: A total of 95.3% of children presented intestinal parasitism, most of whom (94.5%) infected by protozoa and 36.1% infected by soil-transmitted helminths (STH), with Trichuris trichiura (27.3%) being the most prevalent. Multiple infections were found to be high (83.8%), with protozoa and STH co-infections in 30.6%. STH infections were mainly of low/moderate intensity. Neither infection nor STH infection of any intensity profile, was significantly related to anemia. In addition, STH infection, regardless of the intensity profile, was not associated with stunting, underweight or thinness. There was no difference between genders nor among ages in odds of anemia and nutritional status in STH-infected schoolchildren. Conclusion: Multiparasitism remains high among Rwandan schoolchildren and is likely to cause nutritional problems. This work emphasizes the importance of keeping up health programs to reduce the prevalence of infection

Differences in the clinical management of women and men after detection of a solitary pulmonary nodule in clinical practice

Objectives To explore differences in the clinical management of men and women in the 5 years after detecting a solitary pulmonary nodule (SPN) by chest radiograph or CT in routine clinical practice. Methods We followed up 545 men and 347 women with an SPN detected by chest radiograph or CT in a retrospective cohort of 25,422 individuals undergoing routine thoracic imaging in 2010–2011.We compared the frequency of each management strategy (no further test, immediate intervention or follow up) according to sex by means of chi-squared.We estimated the relative risk of women versus men of having been followed up instead of an immediate intervention using multivariate logistic regression. We compared by sex the time between detection of the nodule and lung cancer diagnosis, the time between diagnosis and death by means of Mann-Whitney U test and the cumulative effective dose of radiation in each management strategy by means of t test. Results Women were more likely than men to have follow-up rather than immediate intervention (aRR = 1.8, CI 1.3–2.7, p = 0.002), particularly in those who underwent CT (aRR = 4.2, CI 1.9–9.3, p < 0.001). The median time between SPN detection and lung cancer diagnosis was higher in women (4.2 months, interquartile range (IQR) 5.1) than in men (1.5 months, IQR 16.2). The mean cumulative effective dose was 21.3 mSv, 19.4 mSv in men and 23.9mv in women (p = 0.023). Conclusions Our results could reflect decisions based on a greater suspicion of lung cancer in men. The incidental detection of SPNs is increasing, and it is necessary to establish clear strategies aimed to reduce variability in their management according to patient’s sex

Adaptation and psychometric validation of Diabetes Health Profile (DHP-18) in patients with type 2 diabetes in Quito, Ecuador : a cross-sectional study

The Diabetes Health Profile (DHP-18), structured in three dimensions (psychological distress (PD), barriers to activity (BA) and disinhibited eating (DE)), assesses the psychological and behavioural burden of living with type 2 diabetes. The objectives were to adapt the DHP-18 linguistically and culturally for use with patients with type 2 DM in Ecuador, and to evaluate its psychometric properties. Participants were recruited using purposive sampling through patient clubs at primary health centres in Quito, Ecuador. The DHP-18 validation consisted in the linguistic validation made by two Ecuadorian doctors and eight patient interviews. And in the psychometric validation, where participants provided clinical and sociodemographic data and responded to the SF-12v2 health survey and the linguistically and culturally adapted version of the DHP-18. The original measurement model was evaluated with confirmatory factor analysis (CFA). Reliability was assessed through internal consistency using Cronbach's alpha and test-retest reproducibility by administering DHP-18 in a random subgroup of the participants two weeks after (n = 75) using intraclass correlation coefficient (ICC). Convergent validity was assessed by establishing previous hypotheses of the expected correlations with the SF12v2 using Spearman's coefficient. Firstly, the DHP-18 was linguistically and culturally adapted. Secondly, in the psychometric validation, we included 146 participants, 58.2% female, the mean age was 56.8 and 31% had diabetes complications. The CFA indicated a good fit to the original three factor model (χ2 (132) = 162.738, p −0.40 in two of three hypotheses). The original three factor model showed good fit to the data. Although reliability parameters were adequate for PD and DE dimensions, the BA presented lower internal consistency and future analysis should verify the applicability and cultural equivalence of some of the items of this dimension to Ecuador

Factors associated with false negative and false positive results of prostate-specific antigen (PSA) and the impact on patient health

Prostate-specific antigen (PSA) is the main tool for early detection, risk stratification and monitoring of prostate cancer (PCa). However, there are controversies about the use of PSA as a population screening test because of the high potential for overdiagnosis and overtreatment associated. The net benefit of screening is unclear and according to the available recommendations, it should be offered to well-informed men with an adequate health status and a life-expectancy of at least 10 years or to men at elevated risk of having PCa. In addition, the factors that influence test results are unclear, as is impact of false positive or negative results on patient health. Our objective is to assess the clinical and analytical factors associated with the presence of false positive and false negative results and the diagnostic/therapeutic process followed by these patients. Methods and analysis: A prospective observational cohort study will be carried out. We will include a cohort of patients with a positive PSA result (1.081 patients) and a sample of patients with negative results (572 patients); both will be followed for 2 years by reviewing medical records to assess the variables associated with these results, as well as characteristics of patient management after a positive PSA value. We will include those patients with a PSA determination from 2 hospitals in the Valencian Community. Patients who have been previously diagnosed with prostate cancer or who are being followed for previous high PSA values will be excluded. Discussion: The study will estimate the frequency of false positive and false negative PSA results in routine clinical practice, and allow us to quantify the potential harm cause

Evidence for Transmission of Taenia solium Taeniasis/Cysticercosis in a Rural Area of Northern Rwanda

Cysticercosis is a parasitic infection caused by the metacestode larval stage (cysticercus) of Taenia solium. In humans, cysticercosis may infect the central nervous system and cause neurocysticercosis, which is responsible for over 50,000 deaths per year worldwide and is themajor cause of preventable epilepsy cases, especially in low-income countries. Cysticercosis infection is endemic in many less developed countries where poor hygiene conditions and free-range pig management favor their transmission. A cross-sectional study was conducted in 680 children from a rural primary school in Gakenke district (Northern province of Rwanda). Stool samples were collected from participants and analyzed using the Kato-Katz method (KK), formol-ether concentration (FEC), and/or copro-antigen enzyme-linked immunosorbent assay (CoAg-ELISA) to detect taeniasis. Blood samples were collected and analyzed using enzyme-linked immunoelectrotransfer blot (EITB) and antigen enzyme-linked immunosorbent assay (Ag-ELISA) to detect human cysticercosis. The overall proportion of taeniasis positivity was 0.3%(2/680), and both cases were also confirmed by CoAg-ELISA. A total of 13.3% (76/572) of the children studied were positive to cysticercosis (T. solium-specific serum antibodies detected by EITB), of whom 38.0% (27/71) had viable cysticercus (T. solium antigens by Ag-ELISA). This study provides evidence of the highest cysticercosis prevalence reported in Rwanda in children to date. Systematic investigations into porcine and human cysticercosis as well as health education and hygiene measures for T. solium control are needed in Gakenke district

Delineating the psychiatric and behavioral phenotype of recurrent 2q13 deletions and duplications

Recurrent deletions and duplications at the 2q13 locus have been associated with developmental delay (DD) and dysmorphisms. We aimed to undertake detailed clinical characterization of individuals with 2q13 copy number variations (CNVs), with a focus on behavioral and psychiatric phenotypes. Participants were recruited via the Unique chromosomal disorder support group, U.K. National Health Service Regional Genetics Centres, and the DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources (DECIPHER) database. A review of published 2q13 patient case reports was undertaken to enable combined phenotypic analysis. We present a new case series of 2q13 CNV carriers (21 deletion, 4 duplication) and the largest ever combined analysis with data from published studies, making a total of 54 deletion and 23 duplication carriers. DD/intellectual disabilities was identified in the majority of carriers (79% deletion, 70% duplication), although in the new cases 52% had an IQ in the borderline or normal range. Despite the median age of the new cases being only 9 years, 64% had a clinical psychiatric diagnosis. Combined analysis found attention deficit hyperactivity disorder (ADHD) to be the most frequent diagnosis (48% deletion, 60% duplication), followed by autism spectrum disorders (33% deletion, 17% duplication). Aggressive (33%) and self-injurious behaviors (33%) were also identified in the new cases. CNVs at 2q13 are typically associated with DD with mildly impaired intelligence, and a high rate of childhood psychiatric diagnosesparticularly ADHD. We have further characterized the clinical phenotype related to imbalances of the 2q13 region and identified it as a region of interest for the neurobiological investigation of ADHD

Contextualizing Evidence for Action on Diabetes in Low-Resource Settings—Project CEAD Part I: A Mixed-Methods Study Protocol

Challenges remain for policy adoption and implementation to tackle the unprecedented and relentless increase in obesity, diabetes and other non-communicable diseases (NCDs), especially in low- and middle-income countries. The aim of this mixed-methods study is to analyse the contextual relevance and applicability to low-resource settings of a sample of evidence-based healthy public policies, using local knowledge, perceptions and pertinent epidemiological data. Firstly, we will identify and prioritise policies that have the potential to reduce the burden of diabetes in low-resource settings with a scoping review and modified Delphi method. In parallel, we will undertake two cross-sectional population surveys on diabetes risk and morbidity in two low-resource settings in Ecuador. Patients, community members, health workers and policy makers will analyse the contextual relevance and applicability of the policy actions and discuss their potential for the reduction in inequities in diabetes risk and morbidity in their population. This study tackles one of the greatest challenges in global health today: how to drive the implementation of population-wide preventative measures to fight NCDs in low resource settings. The findings will demonstrate how local knowledge, perceptions and pertinent epidemiological data can be used to analyse the contextual relevance and applicability of potential policy actions