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Cystic Fibrosis (CF) is the commonest inherited genetic disorder in Caucasians due to a mutation in the gene CFTR (Cystic Fibrosis Transmembrane Conductance Regulator), and it should be considered as an Inherited Colorectal Cancer (CRC) Syndrome. In the United States, physicians of CF Foundation established the “Developing Innovative Gastroenterology Speciality Training Program” to increase the research on CF in gastrointestinal and hepatobiliary diseases. The risk to develop a CRC is 5–10 times higher in CF patients than in the general population and even greater in CF patients receiving immunosuppressive therapy due to organ transplantation (30-fold increased risk relative to the general population). Colonoscopy should be considered the best screening for CRC in CF patients. The screening colonoscopy should be started at the age of 40 in CF patients and, if negative, a new colonoscopy should be performed every 5 years and every 3 years if adenomas are detected. For transplanted CF patients, the screening colonoscopy could be started at the age of 35, in transplanted patients at the age of 30 and, if before, at the age of 30. CF transplanted patients, between the age of 35 and 55, must repeat colonoscopy every 3 years. Our review draws attention towards the clinically relevant development of CRC in CF patients, and it may pave the way for further screenings and studies.

Aim Assess the potential additional benefit from pulse oximetry screening in the early detection of critical congenital heart disease in a country with a well‐developed antenatal ultrasound screening programme. Methods Live‐born infants, pregnancy terminations and stillbirths from 20 weeks’ gestational age, between 2013 and 2015, with critical cardiac defects defined as primary or secondary targets of pulse oximetry screening were identified. Critical defects were those resulting in the death of a fetus or an infant in the first 28 days after birth, or a defect requiring intervention in the first 28 days. Results Two hundred and sixty‐eight infants and Fetuses were identified. Antenatal detection rates improved from 69% to 77% over the study period. An associated co‐morbidity improved antenatal detection rates. Twenty‐seven live‐born infants were diagnosed after discharge: 15 aortic arch obstruction (AAO); 10 d‐loop transposition of the great arteries (d‐TGA), and two total anomalous pulmonary venous drainage (TAPVD). Of these, five with AAO, nine with d‐TGA and likely both with TAPVD could potentially have been detected with oximetry screening. Conclusion The antenatal detection of critical cardiac anomalies continues to improve in New Zealand. Despite high antenatal detection rates for most lesions, universal postnatal oximetry screening has the potential to improve early detection.

BackgroundThe cost and complexity of polymerase chain reaction (PCR) testing is a significant barrier for the diagnosis and treatment of patients infected with hepatitis C virus (HCV). We investigated the cost-effectiveness of various testing strategies using antigen as an alternative to PCR.MethodsWe developed a mathematical model for HCV to estimate the number of newly diagnosed individuals and cases of different stages of liver disease. We compared the following testing strategies: antibody test followed by PCR in case of positive antibody (baseline strategy); antibody test followed by HCV-antigen test (antibody-antigen); antigen test alone; and PCR test alone. We conducted cost-effectiveness analyses considering the costs of HCV testing (of both infected and uninfected individuals) (A1), liver-related complications (A2) and all costs including HCV treatment (A3). The model was parameterized for the country of Georgia, and several sensitivity analyses were conducted to generalize the findings for different settings.ResultsUsing the current standard of testing, 89% of infected individuals were detected. Comparatively, antibody-antigen and antigen testing alone detected 86% and 88% of infected individuals, respectively. PCR testing alone detected 91% of the infected individuals with the remaining 9% dying or spontaneously recovering before testing. In analysis A1, antibody-antigen testing was not found to be essentially cheaper compared to the baseline strategy. In analysis A2, strategies using PCR were cheaper than antigen-based strategies. In analysis A3, antibody-antigen testing was the cheapest strategy, followed by the baseline strategy, and PCR testing alone.ConclusionAntigen testing, either following a positive antibody test or alone, performed almost as well as the current practice of HCV testing. The cost-effectiveness of these strategies strongly depends on the inclusion of treatment costs.Lay summaryCore antigen testing is a reliable alternative test for diagnose HCV infection. Antigen-based strategies may be cost-effective, in particular if treatment costs are considered.HighlightsStrategies using an antigen test to diagnose HCV infection performed reasonably well compared with the traditional antibody- and PCR based approach.According to our study, antigen test alone missed about 3%, and antibody followed by PCR test 2% of HCV infected individuals.The maximum difference in quality-adjusted life expectancy across the different strategies of diagnosing HCV was only one month.

Background Coronavirus disease 2019 (COVID-19) has been highly epidemic in China since January 2020. Rapid detection of the causative agent, severe acute respiratory coronavirus-2 (SARS-CoV-2), is very important due to its high rate of infectivity. This study aimed to clarify the epidemiology and clinical characteristics of COVID-19 outside of Hubei province, China, and to optimize screening strategies for COVID-19 in attempts to contain spread of the virus. Methods This retrospective study included all confirmed cases of COVID-19 in Hunan Provincial People's Hospital (Changsha, China) between January 22 and February 15, 2020. All cases were detected using a real-time reverse transcription polymerase chain reaction assay. The epidemiology and clinical characteristic of these cases were investigated according to outcome in attempts to optimize screening strategies for COVID-19. Results There were 24 confirmed cases of COVID-19 in the fever outpatient department of Hunan Provincial People's Hospital. Three patients were asymptomatic, and 3 exhibited mild and 3 moderate disease. There was a family cluster phenomenon. Conclusion Individuals with COVID-19 can be asymptomatic or exhibit mild manifestations of disease. Close monitoring and an optimized screening strategy for COVID-19 could help deter spread of the virus.

ObjectiveNon-alcoholic fatty liver disease (NAFLD) is prevalent in patients with type 2 diabetes. Here, we estimate the proportion of patients with type 2 diabetes that should be referred to hepatologists according to the European Association for the Study of the Liver (EASL)-European Association for the Study of Diabetes (EASD)-European Association for the Study of Obesity (EASO) Guidelines and evaluate the association between non-invasive biomarkers of steatosis and fibrosis and diabetic complications.Research design and methodsThis is a retrospective analysis of type 2 diabetes patients who attended on a regular basis our diabetes clinic between 2013 and 2018 (n=2770). Steatosis was assessed using Fatty Liver Index (FLI), Hepatic Steatosis Index and NAFLD Ridge Score and fibrosis using NAFLD Fibrosis Score (NFS), Fibrosis-4 (FIB-4), aspartate aminotransferase (AST) to platelet ratio index (APRI) and AST/alanine aminotransferase (ALT) ratio. Outcome measures were altered albumin excretion rate (AER), chronic kidney disease (CKD) and cardiovascular disease (CVD).ResultsThe prevalence of advanced fibrosis varied from 1% (APRI) to 33% (NFS). The application of the guidelines using a sequential combination of FLI and FIB-4 would lead to referral of 28.3% of patients when using standard FIB-4 cut-offs, while this number dropped to 13.4% when age-adjusted FIB-4 thresholds were applied. A higher prevalence of altered AER was associated with liver steatosis (FLI: OR: 3.49; 95% CI 2.05 to 5.94, pConclusionsWhile specific fibrosis scores identify different proportion of patients with advanced fibrosis, the use of age-adjusted FIB-4 cut-offs leads to a drop in gray-zone results, making referrals to hepatologists more sustainable. Interestingly non-invasive biomarkers were consistently associated with a different pattern of diabetic complications.

Objective. Resistance to standard chemotherapy poses a major clinical problem in the treatment of ovarian cancer patients. Adult-type granulosa cell tumor (AGCT) is a unique ovarian cancer subtype for which efficient treatment options are lacking in advanced disease. To this end, systematic drug response and transcriptomics profiling were performed to uncover new therapy options for AGCTs. Methods. The responses of three primary and four recurrent AGCTs to 230 anticancer compounds were screened in vitro using a systematic drug sensitivity and resistance testing (DSRT) platform, coupled with mRNA sequencing. The responses of the AGCTs were compared with those of human granulosa luteal cells and bone marrow mononuclear cells. Results. Patient-derived AGCT cells showed selective sensitivity to the Src family tyrosine kinase inhibitor dasatinib. A combination of either dasatinib or an mTOR-inhibitor everolimus with paclitaxel resulted in synergistic inhibition of AGCT cell viability. The key kinase targets of dasatinib and members of the mTOR pathway were constantly expressed at mRNA and protein levels, indicating multikinase signal addictions in the AGCT cells. Transcriptomic characterization of the tumors revealed no known oncogenic mutations, suggesting that the drug sensitivity of AGCTs was rather conveyed by selective target expression. Conclusions. We used a systematic functional approach to reveal novel treatment options for a unique gynecological cancer. The selective synergy found between taxanes and dasatinib or mTOR inhibitors warrants further clinical investigations of these combinations in relapsed or aggressive AGCTs and demonstrate that high throughput drug screening and molecular profiling can provide an effective approach to uncover new therapy options. (C) 2016 Elsevier Inc. All rights reserved.

ObjectiveMaturity-onset diabetes of the young caused by hepatocyte nuclear factor-1 alpha (HNF1A) variants (HNF1A-MODY) is a common form of monogenetic diabetes. Although patients with HNF1A-MODY might specifically benefit from sulfonylurea treatment, available methods for screening this specific type of diabetes are not cost-effective. This study was designed to establish an optimized clinical strategy based on multiple biomarkers to distinguish patients with HNF1A-MODY from clinically diagnosed early-onset type 2 diabetes (EOD) for genetic testing in a Chinese population.Research design and methodsA case–control study including 125 non-related young patients with EOD and 15 probands with HNF1A-MODY (cohort 1) was conducted to evaluate reported biomarkers for HNF1A-MODY. A cut-off for the fasting insulin (Fins) level, the 97.5 percentile of 150 healthy subjects with normal components of metabolic syndrome (cohort 2), was used to filter out individuals with obvious insulin resistance (Fins HNF1A-CSS) was established, and its effectiveness was assessed in another group of 410 young patients with EOD (cohort 3).ResultsIn cohort 1, body mass index (BMI), serum high-density lipoprotein cholesterol (HDL-c) and high-sensitivity C reactive protein (hs-CRP) levels were confirmed to be useful for the differential diagnosis of HNF1A-MODY. In cohort 3, eight probands with HNF1A-MODY were identified. In cohort 3 and young relatives with HNF1A-MODY, meeting three of four criteria (BMI 2, hs-CRP 1.12 mmol/L), the sensitivity and specificity of HNF1A-CSS were 100% and 69.3%, respectively. In the pooled analysis of all young patients, HNF1A-CSS displayed 90.5% sensitivity and 73.6% specificity for identifying patients with HNF1A-MODY among those with clinically diagnosed EOD.ConclusionOur HNF1A-CSS is useful for distinguishing patients with HNF1A-MODY from patients with EOD in a young Chinese population.

Objectives This study is to examine the association between different diagnostic criteria for gestational diabetes mellitus (GDM) and adverse birth outcomes. Study Design A retrospective cohort study of 5,937 women with a singleton pregnancy was conducted, who completed GDM screening between 24 to 32 weeks gestational age. Four nonoverlapping groups of women defined as: 1) Normal: glucose challenge test (GCT) Results Prevalences were GDM/CC 4.6%, GDM/IADPSG 3.0, and 7.6% overall. GDM/IADPSG group was associated with increased macrosomia (adj OR [odd ratio] 1.87; 95% CI [confidence interval]: 1.08–3.25; p = 0.02), while GDM/CC group was associated with increased preterm birth (adj OR 1.75; 95% CI: 1.05–2.80; p = 0.03). Conclusion Little difference in birth outcomes was found between the two criteria, GDM/CC and GDM/IADPSG. Randomized controlled trials are needed to clarify the risks and benefits of these screening paradigms before their incorporation into clinical practice.

ObjectiveGuidelines for screening and diagnosis of gestational diabetes mellitus (GDM) have been updated in the past several years, and various inconsistencies exist across these guidelines. Moreover, the quality of these updated guidelines has not been clarified. We thus conducted this systematic review to evaluate the relationship between the quality and detailed recommendations of these guidelines.Data sourcesThe Guidelines International Network Library, the National Institute for Health and Clinical Excellence (NICE) database, the Medline database, the Embase and the National Guidelines Clearinghouse were searched for guidelines containing recommendations on screening and diagnosis strategies for GDM between 2009 and November 2018.MethodsGuidelines included a target group of women with GDM, and contained recommendations for screening and diagnostic strategies for GDM were included in the present systematic review. Reviewers summarised recommendations on screening and diagnosis strategies from each guideline and rated the quality of guidelines by using the Appraisal of Guidelines Research and Evaluation (AGREE) criteria.ResultsA total of 459 citations were collected by the preliminary literature selection, and 16 guidelines that met the inclusion criteria were assessed. The inconsistencies of the guidelines mainly focus on the screening process (one step vs two step) and criteria of oral glucose tolerance test (OGTT) (International Association of Diabetes and Pregnancy Study Groups [IADPSG] vs CarpenterandCoustan). Guidelines with higher AGREE scores usually recommend a one-step OGTT strategy with IADPSG criteria between 24 and 28 gestational weeks, and the majority of these guidelines likely to select evidence by Grading of Recommendations Assessment, Development and Evaluation criteria.ConclusionsThe guidelines of WHO-2013, NICE-2015, American Diabetes Association-2018, Endocrine Society-2013, Society of Obstetricians and Gynaecologists of Canada-2016, International Federation of Gynecology and Obstetrics-2015, American College of Obstetricians and Gynecologists-2018, United States Preventive Services Task Force-2014 and IADPSG-2015 are strongly recommended in the present evaluation, according to the AGREE II criteria. Guidelines with higher quality tend to recommend a one-step 75 g OGTT strategy with IADPSG criteria between 24 and 28 gestational weeks.

Objective To test the ethical acceptability of using financial incentives to increase diabetic retinopathy screening attendance. Background Financial incentives could be an effective way to increase attendance at screening for diabetic retinopathy, although there can be ethical concerns about this approach. Design Survey of people with diabetes in North West London. Those who were due to attend a screening appointment were invited to complete a questionnaire. Key demographic variables included age, gender, and deprivation. Setting and participants A questionnaire was issued to those invited to attend screening in North West London and those who run the screening service. The questionnaire captured views on aspects of the ethical problem and different incentive types. Main variables studied It captured views on the different dimensions of the ethical problem and different types of incentive. In order to understand how views might vary within a population, demographic variables were used to analyze the results. Results and conclusions Vouchers were found to be the most acceptable form of incentive, significantly more so than cash payments. Most rejected the notion of targeting those who need incentivizing, preferring equality. Age was an important factor, with those aged between 40 and 64 the most optimistic about the potential benefits. Higher levels of deprivation were linked to increased acceptability scores. While some ethical concerns are strongly held among certain groups, there is also much support for the principle of incentivizing positive behaviors. This paves the way for future research into the effectiveness of incentivizing diabetic retinopathy screening attendance.

Objective To determine prevalence and factors predictive of periodontitis by using a standardized assessment model in adults with type 2 diabetes. Research design and methods We performed an observational cross-sectional study to determine the burden of periodontitis in adults with type 2 diabetes attending urban, ambulatory referral centers in the USA and UK. Full-mouth probing was performed and periodontitis was diagnosed based on either a low (≥5 mm at ≥1 site) or high pocket probing-depth threshold (≥6 mm at ≥1 site). Results were stratified into a five-stage schema and integrated with other clinical variables into the novel Diabetes Cross-Disciplinary Index to function as a balanced health scorecard. Corresponding demographic and routinely collected health data were obtained and comparisons were made between patients with and without periodontitis. Multivariable logistic regression was performed to identify factors predictive of the presence or absence of periodontitis. Results Between our two cohorts, 253 patients were screened. Caucasians comprised >90% and Hispanic Americans >75% of the UK and US cohorts, respectively. Males and females were equally distributed; mean age was 53.6±11 years; and 17 (6.7%) were edentulous. Of the 236 dentate patients, 128 (54.2%) had periodontitis by low threshold and 57 (24.2%) by high threshold. Just 17 (7.2%) were periodontally healthy. No significant differences in age, HbA1c, blood pressure, body mass index, low-density lipoprotein cholesterol, or smoking status (all p>0.05) were identified between those with or without periodontitis (regardless of threshold) and none was found to be a significant predictor of disease. Conclusions Periodontitis is frequent in adults with type 2 diabetes and all should be screened. Periodontal health status can be visualized with other comorbidities and complications using a novel balanced scorecard that could facilitate patient–clinician communication, shared decision-making, and prioritization of individual healthcare needs.

OBJECTIVE To explore the independent effects of gestational diabetes mellitus (GDM) on maternity care and costs. RESEARCH DESIGN AND METHODS Estimates for maternity care resource activity and costs for 4,372 women, of whom 354 (8.1%) were diagnosed with GDM, were generated from data from the Atlantic Diabetes in Pregnancy (ATLANTIC DIP) database. Multivariate regression analysis was applied to explore the effects of GDM on 1) mode of delivery, 2) neonatal unit admission, and 3) maternity care cost, while controlling for a range of other demographic and clinical variables. RESULTS Women with a diagnosis of GDM had significantly higher levels of emergency caesarean section (odds ratio [OR] 1.75 [95% CI 1.08–2.81]), their infants had significantly higher levels of neonatal unit admission (3.14 [2.27–4.34]), and costs of care were 34% greater (25–43) than in women without GDM. Other variables that significantly increased costs were weight, age, primiparity, and premature delivery. CONCLUSIONS GDM plays an independent role in explaining variations in rates of emergency caesarean section, neonatal unit admission, and costs of care, placing a substantial economic burden on maternity care services. Interventions that prevent the onset of GDM have the potential to yield substantial economic and clinical benefits.

New prognostic models are traditionally evaluated using measures of discrimination and risk reclassification, but these do not take full account of the clinical and health economic context. We propose a framework for comparing prognostic models by quantifying the public health impact (net benefit) of the treatment decisions they support, assuming a set of predetermined clinical treatment guidelines. The change in net benefit is more clinically interpretable than changes in traditional measures and can be used in full health economic evaluations of prognostic models used for screening and allocating risk reduction interventions. We extend previous work in this area by quantifying net benefits in life years, thus linking prognostic performance to health economic measures; by taking full account of the occurrence of events over time; and by considering estimation and cross-validation in a multiple-study setting. The method is illustrated in the context of cardiovascular disease risk prediction using an individual participant data meta-analysis. We estimate the number of cardiovascular-disease-free life years gained when statin treatment is allocated based on a risk prediction model with five established risk factors instead of a model with just age, gender and region. We explore methodological issues associated with the multistudy design and show that cost-effectiveness comparisons based on the proposed methodology are robust against a range of modelling assumptions, including adjusting for competing risks. Copyright © 2011 John Wiley & Sons, Ltd.

There is no consensus on optimal screening procedures for multidrug-resistant Enterobacteriaceae (MDRE) in intensive care units (ICUs). Therefore, we assessed five strategies for the detection of extended-spectrum beta-lactamase (ESBL) and high-level expressed AmpC cephalosporinase (HL-CASE) producers. During a 3-month period, a rectal screening swab sample was collected daily from every ICU patient, from the first 24 h to the last day of ICU stay. Samples were plated on MDRE-selective media. Bacteria were identified using MALDI-TOF mass spectrometry and antibiograms were performed using disk diffusion. MDREs were isolated from 682/2348 (29.0%) screening samples collected from 93/269 (34.6%) patients. Incidences of patients with ESBL and HL-CASE producers were 17.8 and 19.3 per 100 admissions, respectively. In 48/93 patients, MDRE carriage was intermittent. Compared with systematic screening at admission, systematic screening at discharge did not significantly increase the rate of MDRE detection among the 93 patients (62% vs. 70%). In contrast, screening at admission and discharge, screening at admission and weekly thereafter, and screening at admission and weekly thereafter and at discharge significantly increased MDRE detection (77%, p 0.02; 76%, p 0.01; 86%, p