Network proximity analysis as a theoretical model for identifying potential novel therapies in primary sclerosing cholangitis.

Primary Sclerosing Cholangitis (PSC) is a progressive cholestatic liver disease with no licensed therapies. Previous Genome Wide Association Studies (GWAS) have identified genes that correlate significantly with PSC, and these were identified by systematic review. Here we use novel Network Proximity Analysis (NPA) methods to identify already licensed candidate drugs that may have an effect on the genetically coded aspects of PSC pathophysiology.Over 2000 agents were identified as significantly linked to genes implicated in PSC by this method. The most significant results include previously researched agents such as metronidazole, as well as biological agents such as basiliximab, abatacept and belatacept. This in silico analysis could potentially serve as a basis for developing novel clinical trials in this rare disease.

Patient Priorities in Autoimmune Hepatitis: The Need for Better Treatments, More Education and Challenging Stigma.

BACKGROUND: Data show that patients with autoimmune hepatitis have significantly reduced quality-of-life and that corticosteroids carry marked side effects. AIMS: This study explored patients' experiences of autoimmune hepatitis and its treatments; key aspects for developing safe and effective new approaches to therapy. METHODS: An anonymised, internet-based survey collected data including patient demographics, treatments, side-effects, impact on day-to-day life, sources of support and attitudes towards autoimmune hepatitis between December 2019-January 2020. Semi-structured interviews were conducted with 13 patients to further explore their support networks, treatment experiences and health priorities. Descriptive and quantitative analyses were undertaken using R and free text responses were subject to thematic analysis. RESULTS: In total, 270 survey responses were received (median age 55 years and 94% female). Perceived medication side-effects were reported by 66% (169/257) and 73% responded negatively about their experience of corticosteroids. The majority (62·3% [(109/175]) would 'definitely' or 'probably' consider clinical trial participation to improve their care. Only 18·7% (31/166) reported access to a specialist liver nurse and nearly half were involved in support groups. Interview and survey data suggested that major issues were stigma, loss of control and fatigue. CONCLUSIONS: This study provides insights into the realities of living with autoimmune hepatitis with clear issues around lack of support networks, need for patient empowerment and stigma surrounding liver disease. Patient priorities are better therapies to slow disease progression, avoiding corticosteroids and minimising side-effects. Patient willingness to participate in trials suggests that they are achievable provided they have the right design and clinical endpoints.

Patient ownership of primary biliary cholangitis long-term management.

Objective: Patient ownership of disease is vital in rare diseases like primary biliary cholangitis (PBC). This survey of UK members of the PBC foundation aimed to assess patients' perception of their disease management, focusing on key biomarkers and problematic symptoms. Design: Registered PBC foundation members were surveyed on their experiences on their most recent clinic visit, covering the type of hospital and clinician and whether biochemical response and symptom burden were discussed, including who initiated these conversations. Respondents were also asked about their willingness to initiate these conversations. Results: Across 633 respondents, 42% remembered discussing alkaline phosphatase, the key biochemical response measure, and the majority of discussions were initiated by the healthcare provider. 56% of respondents remembered discussing itch, a key PBC symptom. There was no distinction between the grade of healthcare professional, but both patients and clinicians were significantly more likely to discuss symptoms over disease progression. Reassuringly, 84% of respondents felt willing to initiate conversations about their illness, regardless of the grade of managing clinician. Conclusions: This work lays a positive foundation for patient education and empowerment projects, likely to improve clinical outcomes. Key aspects of management (biochemical response to treatment and symptom burden) should be emphasised as topics of discussion to both patients and clinicians managing PBC. We suggest a simple cue card to prompt patient-led discussion.

Managing cognitive symptoms and fatigue in cholestatic liver disease.

Introduction: Patients with cholestatic diseases may develop fatigue and cognitive symptoms. The impact of symptom burden may be significant in some patients. To date, there are no effective pharmacological therapies to improve cognitive symptoms or fatigue in cholestasis and we are wholly reliant on supportive approaches. Area covered: This review provides an overview of cognitive symptoms and fatigue in the cholestatic liver disease primary biliary cholangitis (PBC), including pathophysiology and our approach to the management of these symptoms. Expert opinion: The impact of fatigue and cognitive symptoms on the perceived quality of life can be profound for patients with PBC. The pathophysiology of these symptoms is complex and poorly understood, making the development of therapeutic trials of symptom-directed therapies challenging. The current recommended management for fatigue and cognitive symptoms is mainly supportive.

The Next Generation: How medical students use new Social Media to support their learning.

This article was migrated. The article was marked as recommended. Background The rise of social media [SoMe] has changed medical education practice, possibly facilitating learning through conversational interaction, social feedback and relationships. Usage of newer SoMe tools like Instagram and Snapchat has not been scrutinised.This study aimed to understand how medical students may use newer SoMe tools, specifically Twitter, Instagram & Snapchat, in their learning, in the context of a parallel SoMe course. Methods An optional, parallel SoMe course was established at Newcastle University Medical School. 301 fourth-year medical students were invited to engage using Twitter, Snapchat and Instagram. Evaluation adopted a mixed methods approach, gathering SoMe analytics and survey data as well as qualitative, free-text responses from a questionnaire and focus-group discussion. Results Live-tweeting lectures featured 95 facilitator tweets, with five replies by students. 22 Instagram posts received no student responses, and three Snapchat stories were viewed 15,312 times, with 212 screenshots taken. Of questionnaire respondents, 75% [n=66] stated they engaged with content. Framework analysis of free-text responses and focus group discussion identified peer influence, fear of exposure, cognitive load and curiosity as drivers in new SoMe use. Discussion Medical students may engage with new SoMe for learning. This may manifest as yet another unilateral learning resource, rather than a tool for discussion or debate. Educators should be aware of external influences, such as peer influence, before assuming student interaction. Further research into medical student use of newer SoMe platforms is warranted, given their popularity, rapidly evolving nature and short lifespan.

Public health and environmental response to the first case of naturally acquired inhalational anthrax in the United States in 30 years: infection of a new york city resident who worked with dried animal hides.

In Pennsylvania on February 16, 2006, a New York City resident collapsed with rigors and was hospitalized. On February 21, the Centers for Disease Control and Prevention and the New York City Department of Health and Mental Hygiene were notified that Bacillus anthracis had been identified in the patient's blood. Although the patient's history of working with dried animal hides to make African drums indicated the likelihood of a natural exposure to aerosolized anthrax spores, bioterrorism had to be ruled out first. Ultimately, this case proved to be the first case of naturally occurring inhalational anthrax in 30 years. This article describes the epidemiologic and environmental investigation to identify other cases and persons at risk and to determine the source of exposure and scope of contamination. Because stricter regulation of the importation of animal hides from areas where anthrax is enzootic is difficult, public healthcare officials should consider the possibility of future naturally occurring anthrax cases caused by contaminated hides. Federal protocols are needed to assist in the local response, which should be tempered by our growing understanding of the epidemiology of naturally acquired anthrax. These protocols should include recommended methods for reliable and efficient environmental sample collection and laboratory testing, and environmental risk assessments and remediation.

Immigration and risk of childhood lead poisoning: findings from a case control study of New York City children.

OBJECTIVES: We investigated whether foreign birthplace and residence were associated with an increased risk of childhood lead poisoning. METHODS: We conducted a matched case-control study among New York City children (mean age=3 years) tested for lead poisoning in 2002 (n=203 pairs). Children were matched on age, date of test, and residential area. Blood lead and housing data were supplemented by a telephone survey administered to parents or guardians. Conditional logistic regression analysis was used to examine the relationship of lead poisoning status to foreign birthplace and time elapsed since most recent foreign residence after adjustment for housing and behavioral risk factors. RESULTS: Both foreign birthplace and time since most recent foreign residence had strong adjusted associations with lead poisoning status, with children who had lived in a foreign country less than 6 months before their blood test showing a particularly elevated risk of lead poisoning relative to US-born children with no foreign residential history before their blood test (odds ratio [OR]=10.9; 95% confidence interval [CI]=3.3, 36.5). CONCLUSIONS: Our findings demonstrate an increased risk of lead poisoning among immigrant children.

Developing a comprehensive pesticide health effects tracking system for an urban setting: New York City's approach.

In recent years, there have been substantial investments and improvements in federal and state surveillance systems to track the health effects from pesticide exposure. These surveillance systems help to identify risk factors for occupational exposure to pesticides, patterns in poisonings, clusters of disease, and populations at risk of exposure from pesticide use. Data from pesticide use registries and recent epidemiologic evidence pointing to health risks from urban residential pesticide use make a strong case for understanding better the sale, application, and use of pesticides in cities. In this article, we describe plans for the development of a pesticide tracking system for New York City that will help to elucidate where and why pesticides are used, potential risks to varied populations, and the health consequences of their use. The results of an inventory of data sources are presented along with a description of their relevance to pesticide tracking. We also discuss practical, logistical, and methodologic difficulties of linking multiple secondary data sources with different levels of person, place, and time descriptors.

Pesticide spraying for West Nile virus control and emergency department asthma visits in New York City, 2000.

Pyrethroid pesticides were applied via ground spraying to residential neighborhoods in New York City during July-September 2000 to control mosquito vectors of West Nile virus (WNV). Case reports link pyrethroid exposure to asthma exacerbations, but population-level effects on asthma from large-scale mosquito control programs have not been assessed. We conducted this analysis to determine whether widespread urban pyrethroid pesticide use was associated with increased rates of emergency department (ED) visits for asthma. We recorded the dates and locations of pyrethroid spraying during the 2000 WNV season in New York City and tabulated all ED visits for asthma to public hospitals from October 1999 through November 2000 by date and ZIP code of patients' residences. The association between pesticide application and asthma-related emergency visits was evaluated across date and ZIP code, adjusting for season, day of week, and daily temperature, precipitation, particulate, and ozone levels. There were 62,827 ED visits for asthma during the 14-month study period, across 162 ZIP codes. The number of asthma visits was similar in the 3-day periods before and after spraying (510 vs. 501, p = 0.78). In multivariate analyses, daily rates of asthma visits were not associated with pesticide spraying (rate ratio = 0.92; 95% confidence interval, 0.80-1.07). Secondary analyses among children and for chronic obstructive pulmonary disease yielded similar null results. This analysis shows that spraying pyrethroids for WNV control in New York City was not followed by population-level increases in public hospital ED visit rates for asthma.

The New York City Smoke-Free Air Act: second-hand smoke as a worker health and safety issue.

BACKGROUND: Despite the provisions of a Smoke-Free Air Act (SFAA) enacted in 1995, more than 415,000 non-smoking New York City workers reported exposure to second-hand smoke in the workplace all or most of the time in 2002. Continued exposure to second-hand smoke in New York City prompted a renewed debate about a broader smoke-free air law. METHODS: The approach taken by the New York City Department of Health and Mental Hygiene to make the case for workplace protection from second-hand smoke, counter the opposition's arguments, and ultimately win the support of policymakers and the public for comprehensive smoke-free workplace legislation is described. RESULTS: On December 30, 2002, New York City's Mayor signed the SFAA of 2002 into law, making virtually all workplaces, including restaurants and bars, smoke-free. CONCLUSIONS: Proponents for a stronger law prevailed by defining greater protection from second-hand smoke as a matter of worker health and safety. Efforts to enact smoke-free workplace laws will inevitably encounter strong opposition, with the most common argument being that smoke-free measures will harm businesses. These challenges, however, can be effectively countered and public support for these measures is likely to increase over time by focusing the debate on worker protection from second-hand smoke exposure on the job.

Integrating the New York citywide immunization registry and the childhood blood lead registry.

In February of 2004, the New York City Department of Health and Mental Hygiene completed the integration of its childhood immunization and blood lead test registry databases, each containing over 2 million children. A modular approach was used to build a separate integrated system, called Master Child Index, to include all children in both the immunization and lead test registries. The principal challenge of this integration was to properly align records so that a child represented in one database is matched with the same child in the other database. To accomplish this task as well as to identify internal duplicate records within each database, an artificial intelligence record linkage system was created. The preliminary results show high rates of accurate merging of records both within and between the two databases. The 4,610,585 records contained in both databases before Master Child Index implementation consolidated into 2,977,290 records in the integrated system. The matching system eliminated 523,720 duplicate records within the two databases and matched and merged 1,109,575 records between the two databases. The Department of Health and Mental Hygiene plans to further develop the Master Child Index and use it as the department-wide, record-matching system.

The effect of lead-based paint hazard remediation on blood lead levels of lead poisoned children in New York City.

Despite the widespread use of lead paint hazard control for children with lead poisoning, few controlled studies that estimate the effect of such control on children's blood lead levels have been published. This retrospective follow-up study examined the effects of lead hazard remediation and its timing on the blood lead levels of lead-poisoned children. From the New York City child blood lead registry, 221 children were selected who had an initial blood lead level of 20-44 micro g/dL between 1 July 1994 and 31 December 1996; were 6 months to 6 years of age; had a report of a follow-up blood lead test between 10 and 14 months after the initial test; had a lead-based paint hazard identified in the primary dwelling unit prior to the 10- to 14-month follow-up blood lead test; had resided or spent time at only one address with an identified lead-based paint hazard; and were not chelated. The decline in geometric mean blood lead levels from baseline to 10-14 months later was compared for children whose homes were remediated and whose homes were not remediated during the follow-up period. Regardless of remediation, geometric mean blood lead levels declined significantly from 24.3 micro g/dL at the initial diagnosis to 12.3 micro g/dL at the 10- to 14-month follow-up blood lead test (P<0.01). Among the 146 children whose homes were remediated the geometric mean blood lead levels declined 53% compared to 41% among the 75 children whose homes were not remediated by the follow-up blood lead test, a remediation effect of approximately 20% (P<0.01). After adjusting for potential confounders, the remediation effect was 11%, although it was no longer significant. Race was the only factor that appeared to confound the relationship: Black children had higher follow-up blood lead levels even after controlling for other factors, including the natural logarithm of the initial blood lead level. The effect of remediation appeared to be stronger for younger (10 to <36 months old) than for older (36 to 72 months old) children (P=0.06). While children in homes with earlier remediation (within less than 3 months) appeared to have greater declines in blood lead levels at the follow-up test than children in homes with later remediation (after 3 or more months), this trend was not significant when controlling for confounding factors. The findings of this study suggest that early identification of lead-poisoned children and timely investigation and abatement of hazards contribute to reducing blood lead levels. However, the apparent effect is modest and further research is needed to systematically test and improve the effectiveness of lead hazard controls.

Is home renovation or repair a risk factor for exposure to lead among children residing in New York City?

Children can be lead poisoned when leaded paint is disturbed during home renovation or repair. We conducted a case-control study to assess the association between elevated blood lead levels (BLLs) in children younger than 5 years of age and renovation or repair of homes built before 1950 in New York City. In 1998, we interviewed parents of 106 case children (BLLs >/= 10 micro g/dL) and 159 control children (BLLs

Lead poisoning among pregnant women in New York City: risk factors and screening practices.

This article presents information on pregnant women with incident blood lead levels (BLLs) of 20 microg per deciliter or greater as reported to the New York City Department of Health between September 1996 and June 1999 (n = 33). Almost half of the women were diagnosed during their third trimester of pregnancy, often at their first prenatal visit. The median BLLs at incidence and at last report among women who were retested were 25 and 15 gamma/dL, respectively, a 40% decline. The median incident BLL among newborns (n = 25) was 12 microg/dL. The BLLs were inversely associated with maternal age and length of time in the United States and directly associated with gestational age and pica behavior. Cases were more than twice as likely to be foreign-born women than all women who gave birth in New York City. Prenatal care facilities employing a policy of universal blood lead testing of all pregnant women at the time of their first visit reported disproportionate numbers of cases, accounting for 77% of cases yet only 11% of all births citywide. The findings suggest that (1) the promulgation of recent rules and guidelines for lead risk assessment and screening among pregnant women appears to have been effective in identifying cases that might not have otherwise come to light; (2) case management and environmental interventions were initiated promptly; (3) cases experienced, on average, significant BLL reductions over time; and (4) there is a need for additional public health interventions for pregnant women in urban, multicultural centers. While the data suggest that universal screening may increase case finding among high-risk, immigrant populations, further studies and surveillance are needed to determine systematically the most effective approach.