Establishing a global regulatory floor for children's decisions about participation in clinical research.

BACKGROUND: Enrolling children in clinical trials typically requires parental or guardian permission and, when appropriate, child assent. Aligning requirements across jurisdictions would facilitate multisite pediatric trials. Guidance from the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is the best candidate for a global standard but would benefit from additional specification. METHODS: Ethical analysis of ICH guidance for permission and assent for pediatric trials, with recommendations for clarification. RESULTS: ICH guidance regarding permission and assent would be enhanced by additional detail in the following areas: (1) what information should be provided to parents, guardians, and children considering a trial, and how that information should be provided; (2) the definition of "assent," the criteria for when assent should be required, and the need to include children in discussions even when assent is not mandated; (3) criteria for requiring children's signatures indicating agreement; (4) greater specificity regarding children's right to decline or withdraw; and (5) clarification of when children's wish to decline or withdraw from participation may be overridden and of what the overriding process should entail. CONCLUSION: ICH guidance provides a global standard for decision making regarding children's participation in trials. Several clarifications would facilitate the conduct of multinational pediatric research. IMPACT: Enrolling children in clinical trials requires the permission of a parent/guardian ± the assent of the minor. Differing global regulatory requirements for enrolling children complicate the conduct of multicenter and multinational trials. The authors identify points of ambiguity and/or contradiction in the International Council for Harmonization guidelines and offer recommendations for a common ethical platform for conducting global pediatric research.

Separation of postprandial lipoproteins: improved purification of chylomicrons using an ApoB100 immunoaffinity method.

Elevated levels of triglyceride-rich lipoproteins (TRLs), both fasting and postprandial, are associated with increased risk for atherosclerosis. However, guidelines for treatment are defined solely by fasting lipid levels, even though postprandial lipids may be more informative. In the postprandial state, circulating lipids consist of dietary fat transported from the intestine in chylomicrons (CMs; containing ApoB48) and fat transported from the liver in VLDL (containing ApoB100). Research into the roles of endogenous versus dietary fat has been hindered because of the difficulty in separating these particles by ultracentrifugation. CM fractions have considerable contamination from VLDL (purity, 10%). To separate CMs from VLDL, we produced polyclonal antibodies against ApoB100 and generated immunoaffinity columns. TRLs isolated by ultracentrifugation of plasma were applied to these columns, and highly purified CMs were collected (purity, 90-94%). Overall eight healthy unmedicated adult volunteers (BMI, 27.2 ± 1.4 kg/m2; fasting triacylglycerol, 102.6 ± 19.5 mg/dl) participated in a feeding study, which contained an oral stable-isotope tracer (1-13C acetate). We then used this technique on plasma samples freshly collected during an 8 h human feeding study from a subset of four subjects. We analyzed fractionated lipoproteins by Western blot, isolated and derivatized triacylglycerols, and calculated fractional de novo lipogenesis. The results demonstrated effective separation of postprandial lipoproteins and substantially improved purity compared with ultracentrifugation protocols, using the immunoaffinity method. This method can be used to better delineate the role of dietary sugar and fat on postprandial lipids in cardiovascular risk and explore the potential role of CM remnants in atherosclerosis.

Influence of cuff-occlusion duration on contrast-enhanced ultrasound assessments of calf muscle microvascular blood flow responsiveness in older adults.

NEW FINDINGS: What is the central question of the study? Cuff-occlusion duration may influence contrast-enhanced ultrasound (CEUS) assessments of skeletal muscle microvascular blood flow responsiveness: what are the effects of 1, 3 and 5 min cuff-occlusion on the magnitude and reliability of calf muscle microvascular blood flow responsiveness in older adults? What is the main finding and its importance? Calf muscle microvascular blood flow responsiveness was enhanced following 5 min cuff-occlusion compared with 1 min. The reliability of post-occlusion CEUS measurements was also improved following 5 min occlusion. The use of a standardized 5 min occlusion period should therefore be considered in future studies and clinical practice. ABSTRACT: Contrast-enhanced ultrasound (CEUS) is increasingly used in assessments of skeletal muscle microvascular blood flow responsiveness. In response to limb cuff-occlusion, some studies have reported significant impairments in CEUS measurements of microvascular blood flow in older adults with cardiovascular or metabolic disease, whereas others have failed to detect significant between-group differences, which has brought the reliability of the technique into question. In the absence of a standardized CEUS protocol, there is variance in the duration of cuff-occlusion used, which is likely to influence post-occlusion measurements of muscle microvascular blood flow. We aimed to determine the effect of cuff-occlusion duration by comparing the magnitude and reliability of CEUS measurements of calf muscle microvascular blood flow responsiveness in older adults (n = 15, 67 ± 11 years) following 1, 3 and 5 min occlusion periods. Microvascular blood flow (= microvascular volume × microvascular velocity) within the calf muscle was measured using real-time destruction-replenishment CEUS. Measurements were made following thigh cuff-occlusion (200 mmHg) periods of 1, 3 and 5 min in a random order. Microvascular blood flow was higher following 3 min (3.71 ± 1.46 aU s-1 ) and 5 min (3.47 ± 1.48 aU s-1 ) compared with 1 min (2.42 ± 1.27 aU s-1 , P = 0.002), which corresponded with higher microvascular volumes after 3 and 5 min compared with 1 min. Reliability was good following 5 min (intraclass correlation coefficient (ICC) 0.49) compared with poor following 1 min (ICC 0.34) and 3 min (ICC 0.35). This study demonstrates that the magnitude and reliability of calf muscle microvascular responsiveness is enhanced using a 5 min cuff-occlusion protocol compared with 1 min in older adults.

Restoring Christ-centered medicine through public policy changes centered around subsidiarity and the doctor-patient relationship.

Many Catholic leaders supported passage of legislation designed to achieve the humanitarian goal of universal or near-universal health coverage. These leaders could not imagine that the resulting law would lead to a severe assault on the practice of Christ-centered medicine. The legislative focus now is on conscience protection and making the Hyde Amendment permanent. But the real change that is needed is a culture that values life and puts doctors and patients, not secular bureaucracies, at the center of healthcare decisions. Many new proposals are being offered with the shared goals of expanding access to affordable health coverage, allowing people to make their own choices without oppressive government mandates, helping the most vulnerable, and protecting the right of citizens and medical professionals to live and work according to their religious values and principles.

Quality of care for chronic conditions: identifying specificities of quality aims based on scoping review and Delphi survey.

There is a growing need to implement high quality chronic care to address the global burden of chronic conditions. However, to our knowledge, there have been no systematic attempts to define and specify aims for chronic care quality. To address this gap, we conducted a scoping review and Delphi survey to establish and validate comprehensive specifications. The Institute of Medicine's (IOM) quality of care definition and aims were used as the foundation. We purposively selected articles from the scientific (n=48) and grey literature (n=26). We sought papers that acknowledged and unpacked the plurality of quality in chronic care and proposed or utilised frameworks, studied their implementation, or investigated at least two IOM quality care aims and implementation. Articles were analysed both deductively and inductively. The findings were validated through a Delphi survey involving 49 international chronic care experts with varied knowledge of, and experience in, low-and-middle-income countries. Considering the natural history of chronic conditions and the journey of a person with a chronic condition, we defined and identified the aims of chronic care quality. The six IOM aims apply with specific meanings. We identified a seventh aim, continuity, which relates to the issue of chronicity. The group endorsed our specifications and several participants gave contextualised interpretations and concrete examples. Chronic conditions pose specific challenges underscoring the relevance of tailoring quality of care aims. The next steps require a tailored definition and specific aims to improve, measure and assure the quality of chronic care.

Main findings: While previously defined aims of good-quality care may also apply to chronic care quality, the nature of chronic conditions and ensuing healthcare needs warrant specifications for good-quality chronic care.Added knowledge: Our proposed definition and specific aims are tailored to the natural history of chronic conditions, and can serve as a guide on determining what can be deemed as good-quality chronic care.Global health impact for policy and action: This work, developed to guide further work on designing purchasing instruments to improve quality of chronic care, particularly in low- and middle-income countries, may also be a source of inspiration for other interventions aiming at improving quality of chronic care.

The effectiveness of text messages support for diabetes self-management: protocol of the TEXT4DSM study in the democratic Republic of Congo, Cambodia and the Philippines.

BACKGROUND: People with diabetes find it difficult to sustain adequate self-management behaviour. Self-Management Support strategies, including the use of mobile technology, have shown potential benefit. This study evaluates the effectiveness of a mobile phone support intervention on top of an existing strategy in three countries, DR Congo, Cambodia and the Philippines to improve health outcomes, access to care and enablement of people with diabetes, with 480 people with diabetes in each country who are randomised to either standard support or to the intervention. DESIGN/METHODS: The study consists of three sub-studies with a similar design in three countries to be independently implemented and analysed. The design is a two-arm Randomised Controlled Trial, in which a total of 480 adults with diabetes participating in an existing DSME programme will be randomly allocated to either usual care in the existing programme or to usual care plus a mobile phone self-management support intervention. Participants in both arms complete assessments at baseline, one year and two years after inclusion.Glycosylated haemoglobin blood pressure, height, weight, waist circumference will be measured. Individual interviews will be conducted to determine the patients' assessment of chronic illness care, degree of self-enablement, and access to care before implementation of the intervention, at intermediate moments and at the end of the study.Analyses of quantitative data including assessment of differences in changes in outcomes between the intervention and usual care group will be done. A probability of <0.05 is considered statistically significant. Outcome indicators will be plotted over time. All data are analysed for confounding and interaction in multivariate regression analyses taking potential clustering effects into account.Differences in outcome measures will be analysed per country and realistic evaluation to assess processes and context factors that influence implementation in order to understand why it works, for whom, under which circumstances. A costing study will be performed. DISCUSSION: The intervention addresses the problem that the greater part of diabetes management takes place without external support and that many challenges, unforeseen problems and questions occur at moments in between scheduled contacts with the support system, by exploiting communication technology. TRIAL REGISTRATION: ISRCTN86247213.

The barriers and facilitators of implementing a national laboratory-based AMR surveillance system in Cambodia: key informants' perspectives and assessments of microbiology laboratories.

Background: Collecting data on antimicrobial resistance (AMR) is an essential approach for defining the scope of the AMR problem, developing evidence-based interventions and detecting new and emerging resistances. Our study aimed to identify key factors influencing the implementation of a laboratory-based AMR surveillance system in Cambodia. This will add additional insights to the development of a sustainable and effective national AMR surveillance system in Cambodia and other low- and middle-income countries. Methods: Key informants with a role in governing or contributing data to the laboratory-based surveillance system were interviewed. Emerging themes were identified using the framework analysis method. Laboratories contributing to the AMR surveillance system were assessed on their capacity to conduct quality testing and report data. The laboratory assessment tool (LAT), developed by the World Health Organisation (WHO), was adapted for assessment of a diagnostic microbiology laboratory covering quality management, financial and human resources, data management, microbiology testing performance and surveillance capacity. Results: Key informants identified inadequate access to laboratory supplies, an unsustainable financing system, limited capacity to collect representative data and a weak workforce to be the main barriers to implementing an effective surveillance system. Consistent engagement between microbiology staff and clinicians were reported to be a key factor in generating more representative data for the surveillance system. The laboratory assessments identified issues with quality assurance and data analysis which may reduce the quality of data being sent to the surveillance system and limit the facility-level utilisation of aggregated data. A weak surveillance network and poor guidance for outbreak response were also identified, which can reduce the laboratories' opportunities in detecting critical or emerging resistance occurring in the community or outside of the hospital's geographical coverage. Conclusion: This study identified two primary concerns: ensuring a sustainable and quality functioning of microbiology services at public healthcare facilities and overcoming sampling bias at sentinel sites. These issues hinder Cambodia's national AMR surveillance system from generating reliable evidence to incorporate into public health measures or clinical interventions. These findings suggest that more investments need to be made into microbiology diagnostics and to reform current surveillance strategies for enhanced sampling of AMR cases at hospitals.

Virtual teaching kitchen classes and cardiovascular disease prevention counselling among medical trainees.

Background: Hands-on culinary medicine education for medical trainees has emerged as a promising tool for cardiovascular health promotion. Purpose: To determine whether virtual culinary medicine programming associates with Mediterranean diet (MedDiet) adherence and lifestyle medicine competencies among medical trainees across the USA. Method: A total of 1433 medical trainees across 19 sites over a 12-month period were included. The Cooking for Health Optimisation with Patients-Medical Trainees survey composed of 61 questions regarding demographics, nutritional attitudes, dietary habits including MedDiet score and lifestyle medicine counselling competencies. Multivariable logistic regression assessed the association of virtual culinary medicine education with MedDiet intake and nutritional attitudes. Results: There were 519 medical trainees who participated in virtual culinary medicine education and 914 medical trainees who participated in their standard nutrition curricula. More than one-half of participants were women (n=759) and the mean age was 27 years old. Compared with students enrolled in traditional nutrition curricula, participants in virtual culinary medicine education were 37% more likely to adhere to MedDiet guidelines for fruit intake (OR 1.37, 95% CI 1.03 to 1.83, p=0.03). Virtual culinary medicine education was associated with higher proficiency in lifestyle medicine counselling categories, notably recommendations involving fibre (OR 4.03; 95% CI 3.05 to 5.34), type 2 diabetes prevention (OR 4.69; 95% CI 3.51 to 6.27) and omega fatty acids (OR 5.21; 95% CI 3.87 to 7.02). Virtual culinary medicine education had a similar, although higher magnitude association with MedDiet counselling competency (OR 5.73, 95% CI 4.26 to 7.70) when compared with historical data previously reported using hands-on, in-person culinary medicine courseware (OR 4.97, 95% CI 3.89 to 6.36). Conclusions: Compared with traditional nutritional educational curricula, virtual culinary medicine education is associated with higher MedDiet adherence and lifestyle medicine counselling competencies among medical trainees. Both virtual and hands-on culinary medicine education may be useful for cardiovascular health promotion.

Prevalence of elevated alanine aminotransferase (ALT) in pregnancy: A cross-sectional labor and delivery-based assessment.

Since liver tests are not routinely checked in pregnancy, the prevalence of abnormal liver tests and liver-related abnormalities in pregnancy in a US-based population is not known. We sought to determine the prevalence of abnormal alanine aminotransferase (ALT) among pregnant Individuals who present to labor and delivery for evaluation and to evaluate prevalence of underlying diagnosed liver conditions. Prospective study evaluating liver tests in consecutive samples obtained on the labor and delivery unit. Patient characteristics were compared between those with and without abnormal ALT and those with and without abnormal ALT without a liver-related diagnosis made in clinical practice, using t tests for continuous measures and χ2 or Fisher's exact tests as appropriate for categorical measures. Logistic regression was utilized to identify factors associated with abnormal ALT in this subcohort to determine predictors of abnormal ALT in those without a known liver-related diagnosis. We collected 1024 laboratory specimens from 996 patients. Of these patients, 131 of 996 (13.2%) had elevated ALT ≥25 IU/L; 20 (2%) had ALT ≥50, 6 (0.6%) had ALT ≥125 and 3 (0.3%) had ALT ≥250. 61/131 (46.6%) of patients with ALT ≥25 IU/L had not had LTs checked during routine pregnancy care. 20 (15%) of individuals with abnormal LT had preeclampsia; 5 (4%) had cholestasis of pregnancy; 1 (0.8%) had hepatitis C; there were no other chronic liver diseases diagnosed. There were no significant demographic or clinical differences between those with and without ALT ≥25, whether liver disease diagnosis was made or not. We identified an over 10% prevalence of abnormal LTs in consecutive pregnant individuals who presented to L&D, most of whom did not have a liver-related condition diagnosed in clinical practice. Among those with liver-related diagnoses, PE and ICP were the most common among individuals with ALT≥25 IU/mL, with chronic liver disease rarely diagnosed. Further evaluation of the role of ALT testing as part of routine prenatal care is needed, particularly in establishing a baseline prevalence of liver test abnormalities in pregnancy and independent association with pregnancy outcomes.

Effects of Setting on Psychedelic Experiences, Therapies, and Outcomes: A Rapid Scoping Review of the Literature.

The health and well-being impacts of art and aesthetic experiences have been rigorously studied by a range of disciplines, including cognitive neuroscience, psychiatry, public health, and translational clinical research. These experiences, encompassed in the concepts of set and setting, have long been claimed to be pivotal in determining the acute and enduring effects of psychedelic experiences. Responding to the field's longstanding emphasis on the role and value of setting, a rapid scoping review was undertaken to identify the extent to which effects of setting and aesthetics on psychedelic experiences and therapies have been explicitly studied. It offers an analysis of the strengths and limitations of the extant literature and discusses evidentiary gaps as well as evidentiary opportunities for the field. The 43 included studies indicate apparent consensus regarding the importance of setting in psychedelic therapies, as well as consistent interest in theorizing about these effects. However, this consensus has yet to generate consistent, prospective, rigorous tests of setting and its complexities. As a result, the field continues to lack understanding or agreement regarding the effects of various specific elements of setting, the mechanisms by which they affect outcomes, for whom these effects occur, under what circumstances, given what conditions, and other critical factors. Further studies of setting and aesthetics in the context of psychedelic therapies are likely to not only improve these therapies and their delivery, but also inform considerations of setting and aesthetics for non-psychedelic interventions.

Process evaluation of the scale-up of integrated diabetes and hypertension care in Belgium, Cambodia and Slovenia (the SCUBY Project): a study protocol.

INTRODUCTION: Integrated care interventions for type 2 diabetes (T2D) and hypertension (HT) are effective, yet challenges exist with regard to their implementation and scale-up. The 'SCale-Up diaBetes and hYpertension care' (SCUBY) Project aims to facilitate the scale-up of integrated care for T2D and HT through the co-creation and implementation of contextualised scale-up roadmaps in Belgium, Cambodia and Slovenia. We hereby describe the plan for the process and scale-up evaluation of the SCUBY Project. The specific goals of the process and scale-up evaluation are to (1) analyse how, and to what extent, the roadmap has been implemented, (2) assess how the differing contexts can influence the implementation process of the scale-up strategies and (3) assess the progress of the scale-up. METHODS AND ANALYSIS: A comprehensive framework was developed to include process and scale-up evaluation embedded in implementation science theory. Key implementation outcomes include acceptability, feasibility, relevance, adaptation, adoption and cost of roadmap activities. A diverse range of predominantly qualitative tools-including a policy dialogue reporting form, a stakeholder follow-up interview and survey, project diaries and policy mapping-were developed to assess how stakeholders perceive the scale-up implementation process and adaptations to the roadmap. The role of context is considered relevant, and barriers and facilitators to scale-up will be continuously assessed. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Institutional Review Board (ref. 1323/19) at the Institute of Tropical Medicine (Antwerp, Belgium). The SCUBY Project presents a comprehensive framework to guide the process and scale-up evaluation of complex interventions in different health systems. We describe how implementation outcomes, mechanisms of impact and scale-up outcomes can be a basis to monitor adaptations through a co-creation process and to guide other scale-up interventions making use of knowledge translation and co-creation activities.

A systematic library for comprehensive overexpression screens in Saccharomyces cerevisiae.

Modern genetic analysis requires the development of new resources to systematically explore gene function in vivo. Overexpression screens are a powerful method to investigate genetic pathways, but the goal of routine and comprehensive overexpression screens has been hampered by the lack of systematic libraries. Here we describe the construction of a systematic collection of the Saccharomyces cerevisiae genome in a high-copy vector and its validation in two overexpression screens.

Gaucher disease: when molecular testing and clinical presentation disagree -the novel c.1226A>G(p.N370S)--RecNcil allele.

We report a 31 year old woman who had prenatal carrier screening for Ashkenazi Jewish (AJ) genetic diseases and was found to have two acid ß-glucosidase (GBA) mutations, c.1226A>G(p.N370S) and c.1448T>C(p.L444P), consistent with the diagnosis of Type 1 Gaucher disease (GD1). This genotype typically manifests in late-adolescence with hepatosplenomegaly and early-onset bone involvement. The Proband had a normal physical examination, no organomegaly, and normal blood counts, skeletal survey, and bone density. Leukocyte acid ß-glucosidase and plasma chitotriosidase activities were normal. To investigate these unexpected results, her GBA alleles were RT-PCR amplified and sequenced. Five RT-PCR clones were negative for both mutations, while five clones had the c.1226A>G(p.N370S) and c.1448T>C(p.L444P) mutations, along with c.1483G>C(p.A456P), and c.1497G>C(p.V460V) mutations, the latter three lesions composing the rare GBA pseudogene-derived RecNcil allele. Genetic testing misdiagnosed the asymptomatic Proband as affected with Type 1 Gaucher disease; however, molecular studies revealed a novel allele with the two common GBA mutations on the RecNcil background. This allele presumably arose by crossing-over between a c.1226A>G allele and the pseudogene, gene conversion, or a new c.1226A>G mutation on the RecNcil background. This novel complex allele highlights a limitation of carrier screening for GD.

The growing caseload of chronic life-long conditions calls for a move towards full self-management in low-income countries.

BACKGROUND: The growing caseload caused by patients with chronic life-long conditions leads to increased needs for health care providers and rising costs of health services, resulting in a heavy burden on health systems, populations and individuals. The professionalised health care for chronic patients common in high income countries is very labour-intensive and expensive. Moreover, the outcomes are often poor. In low-income countries, the scarce resources and the lack of quality and continuity of health care result in high health care expenditure and very poor health outcomes. The current proposals to improve care for chronic patients in low-income countries are still very much provider-centred.The aim of this paper is to show that present provider-centred models of chronic care are not adequate and to propose 'full self-management' as an alternative for low-income countries, facilitated by expert patient networks and smart phone technology. DISCUSSION: People with chronic life-long conditions need to 'rebalance' their life in order to combine the needs related to their chronic condition with other elements of their life. They have a crucial role in the management of their condition and the opportunity to gain knowledge and expertise in their condition and its management. Therefore, people with chronic life-long conditions should be empowered so that they become the centre of management of their condition. In full self-management, patients become the hub of management of their own care and take full responsibility for their condition, supported by peers, professionals and information and communication tools.We will elaborate on two current trends that can enhance the capacity for self-management and coping: the emergence of peer support and expert-patient networks and the development and distribution of smart phone technology both drastically expand the possibilities for full self-management. CONCLUSION: Present provider-centred models of care for people with chronic life-long conditions are not adequate and we propose 'full self-management' as an alternative for low-income countries, supported by expert networks and smart phone technology.

Corrigendum to: Hepatitis C Seroprevalence Among Consecutive Labor and Delivery Admissions in Two New York City Hospitals.

[This corrects the article DOI: 10.1093/ofid/ofaa514.].

Frequency of unrecognized Fabry disease among young European-American and African-American men with first ischemic stroke.

BACKGROUND AND PURPOSE: The cause of initial ischemic stroke in up to 30% of young patients remains unclear. Fabry disease, due to deficient alpha-galactosidase A (alpha-Gal A) activity, is a vascular endothelial glycosphingolipid storage disease typically presenting in childhood. With advancing age, patients develop renal, cardiac, and cerebrovascular disease and die prematurely. A European study suggested an increased prevalence of unrecognized Fabry disease in patients with cryptogenic stroke. We hypothesized that alpha-Gal A deficiency is a rare cause of initial early-onset ischemic stroke in men. METHODS: The Stroke Prevention in Young Men Study enrolled >550 men (15 to 49 years) with first ischemic stroke in the Baltimore-Washington area in 2004 to 2007. Frozen plasma samples were assayed for alpha-Gal A activity, and DNA from patients with consistently low plasma alpha-Gal A activities were sequenced. RESULTS: The study sample consisted of 558 men (42% African-American; median age 44 years). Stroke was cryptogenic in 154 men (40% African-American). In 10 patients with low plasma alpha-Gal A activities, DNA sequencing identified alterations in the alpha-Gal A gene in 2 patients. The polymorphism, D313Y, which results in low plasma enzyme activity, but near normal levels of cellular activity was seen in one European-American male. The Fabry disease-causing A143T mutation was seen in an African-American male with cryptogenic stroke (0.18% of all strokes: upper 95% CI=0.53%; 0.65% of cryptogenic strokes: upper 95% CI=1.92%). CONCLUSIONS: In this biracial population, unrecognized Fabry disease is a rare but treatable cause of initial ischemic stroke in young men.

Hepatitis C Seroprevalence Among Consecutive Labor and Delivery Admissions in Two New York City Hospitals.

BACKGROUND: Rates of hepatitis C virus (HCV) among women of childbearing age have increased as a result of the opioid epidemic, especially in the nonurban white population. Recently updated US Preventative Services Task Force and Centers for Disease Control and Prevention guidance have recommended universal HCV screening during pregnancy, but obstetrics societies have not yet endorsed this recommendation. We evaluated the seroprevalence of HCV among pregnant women in an inner-city population, compared rates with other sexually transmitted infections (STIs) screened for during pregnancy, and evaluated factors associated with HCV positivity. METHODS: We performed a prospective seroprevalence study of consecutive labor and delivery admissions (both antepartum complications and delivery admissions) by testing serum samples for HCV antibody over 9 months at 2 major hospital settings in New York City. RESULTS: Fifty-six of 7373 (0.75%; 95% confidence interval [CI], 0.57-0.98) patients screened positive for HCV, with 28 of 4013 (0.70%; 95% CI, 0.46%-1.01%) and 28 of 3413 (0.82%; 95% CI, 0.55%-1.18%) at each hospital. Forty-one percent of HCV-positive patients had any reported HCV risk factors. Hepatitis C virus-positive patients were less likely to have private insurance and more likely to have a history of cannabis, cocaine, and injection drug use (P < .001). The HCV rates were higher among antepartum admissions compared with delivery admissions and higher than that of hepatitis B virus (0.65%; 95% CI, 0.48-0.86), human immunodeficiency virus (0.27%; 95% CI, 0.16-0.42), and syphilis (0.16%; 95% CI, 0.08-0.28). CONCLUSIONS: We found a higher than expected HCV seroprevalence among pregnant women and higher than most other STIs routinely screened for in pregnancy. Most patients had no risk factors. These findings support universal screening for hepatitis C during pregnancy.

Type 1 Gaucher disease: null and hypomorphic novel chitotriosidase mutations-implications for diagnosis and therapeutic monitoring.

Human plasma chitotriosidase (Chito) is a useful diagnostic and therapeutic biomarker for Type 1 Gaucher disease (GD). However, approximately 40% of Caucasians are heterozygous or homozygous for a common null mutation, c.1049_1072dup24 (dup24) in the chitotriosidase gene (chitinase 1, CHIT1), that complicates interpretation for heterozygotes and precludes use for null homozygotes. 320 Type 1 GD patients were screened for CHIT1 genotype and plasma Chito enzyme levels; 37% were heterozygous and 4% were homozygous for the CHIT1 dup24 allele. Four patients who had no or very low plasma Chito activities had wild-type (wt)/dup24 or wt/wt CHIT1 genotypes, suggesting the presence of other mutations. Sequencing their CHIT1 genes revealed three novel mutations: p.E74K (E74K), p.G102S (G102S), and a complex exon 10 lesion (c.[1060G>A; 1155G>A; 1156+5_1156+8delGTAA], p.[G354R; L385L; missplicing], designated "complex E/I-10"). The G102S mutation was common in Type 1 GD patients and controls ( approximately 30% of alleles). In contrast, the E74K mutation was rare, present only in three Type 1 GD patients ( approximately 1% of alleles), all of Ashkenazi Jewish (AJ) descent, but it was not found in normal controls. The complex E/I-10 mutation occurred in two Caribbean Hispanic/African Type 1 GD patients and was present in 0 to 6% of alleles among normal controls from different populations. In vitro expression demonstrated that the E74K and G102S alleles had approximately 51% and approximately 23% of wild-type Chito catalytic efficiency, respectively. Expression of the G354R allele alone or with the L385L silent substitution did not produce detectable Chito activity or protein. RNA studies indicated that the complex E/I-10 allele also caused missplicing. Recognition of these mutations, particularly G102S, will facilitate the use and interpretation of plasma Chito activities for disease diagnosis, estimating disease severity, and monitoring therapeutic efficacy in GD.