Antenatal pyelonephritis: a three-year retrospective cohort study of two Irish maternity centres.

Pyelonephritis affects 1-2% of pregnant women, and is associated with significant maternal and fetal morbidity. Antenatal pyelonephritis has been associated with PPROM (preterm premature rupture of membranes), preterm labour, low birth weight (LBW) and prematurity. A three-year retrospective dual-centre cohort study of antenatal pyelonephritis cases was conducted in two neighbouring Irish maternity hospitals - the Rotunda Hospital (RH) and the National Maternity Hospital (NMH). Patient demographics, clinical presentation, investigations, management and maternal/neonatal outcomes were recorded. A total of 47,676 deliveries (24,768 RH; 22,908 NMH) were assessed. 158 cases of antenatal pyelonephritis were identified (n = 88 RH, n = 70 NMH), with an incidence of 0.33%. The median age was 28 years. The median gestation was 27 + 6 weeks, with 51% presenting before 28 weeks' gestation. Risk factors included; obesity (18.4%), diabetes mellitus (13.3%) and self-reported clinical history of recurrent urinary tract infection (28.5%). Rate of relapse with UTI in the same pregnancy was 8.2%. Renal ultrasound was performed in 30.4%. Predominant uropathogens were Escherichia coli (60%), Klebsiella pneumoniae (11%) and Proteus mirabilis (5%). 7.5% of cases had a concurrent bloodstream infection, 13.3% of cases were complicated by sepsis and 1.9% with septic shock. Complications including PPROM (6.3%), preterm delivery < 37 weeks' gestation (11%), LBW < 2,500 g (8.2%) were comparable between sites. Delivery within 72 hours of diagnosis was noted in 7% (n = 11) of patients, of which three were preterm and one had LBW. Appropriate and prompt investigation and management of antenatal pyelonephritis is essential given the associated maternal and neonatal morbidity.

Performance of galactomannan testing from endotracheal aspirate to guide bronchoalveolar lavage in the diagnosis of invasive aspergillosis.

PURPOSE: Invasive aspergillosis is a major threat to immunocompromised individuals. Galactomannan (GM) is used as a biomarker for invasive aspergillosis. Investigations recommended in current guidelines include GM testing of bronchoalveolar lavage (BAL) fluids. GM testing of endotracheal aspirate, the sampling of which is less invasive, less resource-intensive and less aerosol-generating, is not validated. We compared the performance of endotracheal aspirate GM as a screening tool to predict BAL fluid GM-positivity in patients with suspected invasive aspergillosis. METHODS: Of each patient, a pair of corresponding endotracheal aspirate and BAL fluid samples was tested and compared for GM results. Two sample sets were included. The first consisted of 140 consecutive BAL fluid/endotracheal aspirate pairs obtained from 133 patients. The pairs of the second sample set (n = 38) were selected based on the criterion that the BAL tested positive for GM. All specimens were obtained in a German 2,000 bed tertiary care center. RESULTS: Among BAL fluid GM-positive samples, endotracheal aspirate GM demonstrated poor specificity (72%) but high sensitivity (92% in predicting BAL fluid GM of ≥ 0.50 and 91% for BAL fluid GM of ≥ 1.00) and an excellent negative predictive value (98%). The use of a marginally elevated cutoff of 0.63 resulted in an improved specificity (72-81%), without loss of sensitivity. CONCLUSIONS: For screening purposes, one might consider testing endotracheal aspirate for GM, which could help avoid unnecessary BAL.

Challenges of conflict of interest, coordination and collaboration in small island contexts: towards effective tobacco control governance in UK Overseas Territories.

INTRODUCTION: The UK Overseas Territories (UKOTs) are semi-autonomous jurisdictions that face distinctive challenges in implementing tobacco control and protecting policy from industry influence. They are not eligible to become independent parties of the WHO Framework Convention on Tobacco Control (FCTC), although they can apply for treaty extension under the UK's ratification. This study explores the relevance of the FCTC-particularly Article 5.3-for tobacco control governance across a sample of UKOTs. METHODS: From March to May 2019, we interviewed 32 stakeholders across four territories (Anguilla, Bermuda, Cayman Islands, St Helena) at diverse stages in implementing key FCTC measures. Thematic qualitative analysis explored awareness and perceptions in relation to tobacco control. RESULTS: Interviewees' accounts highlight the complexity of protecting health policy from industry influence in a context where the 'tobacco industry' covers a diverse range of actors. Despite not being formally covered by the FCTC, several health officials spoke about the strategic value of invoking Article 5.3 in the context of tensions with economic priorities. Nevertheless, effective tobacco control governance is complicated by territories' reliance on local businesses-including tourism-and close social connections that occasionally blur the lines between private and public spheres. CONCLUSIONS: The UKOTs share many characteristics with other small island jurisdictions, creating distinctive challenges for advancing tobacco control and protecting policy from industry interference. Despite their complex status in relation to WHO and its architecture, these territories benefit from the norms embedded in the FCTC and the systems that support its implementation.

Norms, rules and policy tools: understanding Article 5.3 as an instrument of tobacco control governance.

INTRODUCTION: Article 5.3 of the WHO Framework Convention on Tobacco Control, elaborated via its implementation guidelines, can be understood as a policy instrument comprising norms, rules and policy tools designed to shape practices of policy making and minimise tobacco industry interference. METHODS: This qualitative research is based on in-depth interviews with officials from diverse government sectors and non-governmental organisations across countries (Ethiopia, India, Uganda) that have adopted measures to implement Article 5.3. RESULTS: The data highlight varied perceptions and knowledge of Article 5.3 norms between health and non-health sectors. Health officials typically link its core norm of a fundamental conflict between public health and industry interests to the governance norm of protecting public health policies from industry interference. While officials in sectors beyond health broadly endorsed this core norm, they exhibited more limited awareness of Article 5.3 and its model of governance. The results examine how rules to implement Article 5.3 have been codified, but identify the absence of policy tools necessary to operationalise rules and norms. This limitation, alongside restricted awareness beyond health departments, suggests that political commitments to implement Article 5.3 will have limited impact on practices of stakeholder consultation and policy engagement with the tobacco industry. CONCLUSION: Conceptualising Article 5.3 as a policy instrument helps to explain how its rules and policy tools interact with each other and with broader governance processes. This framework has the potential to enhance understanding of Article 5.3 and help identify opportunities and constraints in its implementation.

Institutional tensions, corporate social responsibility and district-level governance of tobacco industry interference: analysing challenges in local implementation of Article 5.3 measures in Karnataka, India.

INTRODUCTION: Accelerating progress on tobacco control will require Article 5.3 of the WHO Framework Convention on Tobacco Control to be systematically integrated into policies and practices of sectors beyond health at diverse government levels. However, no study has explored implementation challenges of Article 5.3 within multilevel systems such as India, where political decisions on tobacco control occur at diverse government levels, which may constrain action at local level. METHODS: Based on 33 semi-structured interviews with diverse government and civil society stakeholders across four districts in Karnataka, India (Mysore, Mangalore, Bengaluru (rural) and Udupi), this study examines challenges to implement Article 5.3 arising from competing agendas and policies of different actors at multiple levels. RESULTS: Our analysis reveals generally low levels of awareness of Article 5.3 and its guideline recommendations, even among those directly involved in tobacco control at district level. Efforts to implement Article 5.3 were also challenged by competing views on the appropriate terms of engagement with industry actors. Scope to reconcile tensions across competing health, agriculture and commercial agendas was further constrained by the policies and practices of the national Tobacco Board, thereby undermining local implementation of Article 5.3. The most challenging aspect of Article 5.3 implementation was the difficulties in restricting engagement by government officials and departments with tobacco industry corporate social responsibility initiatives given national requirements for such activities among major corporations. CONCLUSIONS: Promoting effective implementation of Article 5.3 in Karnataka will require policymakers to work across policy silos and reconcile tensions across India's national health and economic priorities.

Advancing whole-of-government approaches to tobacco control: Article 5.3 and the challenge of policy coordination in Bangladesh, Ethiopia, India and Uganda.

INTRODUCTION: Despite an extensive evidence base on the diverse economic, environmental and social benefits of tobacco control, difficulties in establishing coordinated national approaches remain a defining challenge for Framework Convention on Tobacco Control (FCTC) implementation. Minimising tobacco industry interference is seen as key to effective coordination, and this paper analyses implementation of Article 5.3 guidelines, exploring implications for whole-of-government approaches to tobacco control in Bangladesh, Ethiopia, India and Uganda. METHODS: Based on 131 semistructured interviews with government officials and other key stakeholders, we explore barriers and facilitators for promoting: (1) horizontal coordination across health and other policy spheres, and (2) vertical coordination across national and subnational governments on Article 5.3 implementation. RESULTS: Our analysis identifies common barriers to coordination across diverse geographical contexts and varying approaches to implementation. They highlight broadly shared experiences of limited understanding and engagement beyond health agencies; restricted responsibility and uncertainty amid conflicting mandates; tensions with wider governance practices and norms; limited capacity and authority of coordination mechanisms; and obstacles to vertical coordination across local, state and national governments. Interview data also indicate important opportunities to advance coordination across sectors and government levels, with Article 5.3 measures capable of informing changes in practices, building support in other sectors, allowing for 'bottom-up' innovation and being shaped by engagement with civil society. CONCLUSION: Supporting effective implementation of Article 5.3 is key to advancing multisectoral approaches to FCTC implementation and tobacco control's contributions to global health and sustainable development.

Longitudinal multiparameter assay of lymphocyte interactions from onset by microfluidic cell pairing and culture.

Resolving how the early signaling events initiated by cell-cell interactions are transduced into diverse functional outcomes necessitates correlated measurements at various stages. Typical approaches that rely on bulk cocultures and population-wide correlations, however, only reveal these relationships broadly at the population level, not within each individual cell. Here, we present a microfluidics-based cell-cell interaction assay that enables longitudinal investigation of lymphocyte interactions at the single-cell level through microfluidic cell pairing, on-chip culture, and multiparameter assays, and allows recovery of desired cell pairs by micromanipulation for off-chip culture and analyses. Well-defined initiation of interactions enables probing cellular responses from the very onset, permitting single-cell correlation analyses between early signaling dynamics and later-stage functional outcomes within same cells. We demonstrate the utility of this microfluidic assay with natural killer cells interacting with tumor cells, and our findings suggest a possible role for the strength of early calcium signaling in selective coordination of subsequent cytotoxicity and IFN-gamma production. Collectively, our experiments demonstrate that this new approach is well-suited for resolving the relationships between complex immune responses within each individual cell.

Marijuana Regulatory Frameworks in Four US States: An Analysis Against a Public Health Standard.

The movement to legalize and regulate retail marijuana is growing. We examined legislation and regulations in the first 4 states to legalize recreational marijuana (Colorado, Washington, Oregon, and Alaska) to analyze whether public health best practices from tobacco and alcohol control to reduce population-level demand were being followed. Only between 34% and 51% of policies followed best practices. Marijuana regulations generally followed US alcohol policy regarding conflict of interest, taxation, education (youth-based and problematic users), warning labels, and research that does not seek to minimize consumption and the associated health effects. Application of US alcohol policies to marijuana has been challenged by some policy actors, notably those advocating public health policies modeled on tobacco control. Reversing past decisions to regulate marijuana modeled on alcohol policies will likely become increasingly difficult once these processes are set in motion and a dominant policy framework and trajectory becomes established. Designing future marijuana legislation to prioritize public health over business would make it easier to implement legalization of recreational marijuana in a way that protects health.

A Public Health Framework for Legalized Retail Marijuana Based on the US Experience: Avoiding a New Tobacco Industry.

Rachel Barry and Stanton Glantz argue that a public health framework that prioritizes public health over business interests should be used by US states and countries that legalize retail marijuana.

Waiting for the opportune moment: the tobacco industry and marijuana legalization.

CONTEXT: In 2012, Washington State and Colorado legalized the recreational use of marijuana, and Uruguay, beginning in 2014, will become the first country to legalize the sale and distribution of marijuana. The challenge facing policymakers and public health advocates is reducing the harms of an ineffective, costly, and discriminatory "war on drugs" while preventing another public health catastrophe similar to tobacco use, which kills 6 million people worldwide each year. METHODS: Between May and December 2013, using the standard snowball research technique, we searched the Legacy Tobacco Documents Library of previously secret tobacco industry documents (http://legacy.library.ucsf.edu). FINDINGS: Since at least the 1970s, tobacco companies have been interested in marijuana and marijuana legalization as both a potential and a rival product. As public opinion shifted and governments began relaxing laws pertaining to marijuana criminalization, the tobacco companies modified their corporate planning strategies to prepare for future consumer demand. CONCLUSIONS: Policymakers and public health advocates must be aware that the tobacco industry or comparable multinational organizations (eg, food and beverage industries) are prepared to enter the marijuana market with the intention of increasing its already widespread use. In order to prevent domination of the market by companies seeking to maximize market size and profits, policymakers should learn from their successes and failures in regulating tobacco.

A second generation human haplotype map of over 3.1 million SNPs.

We describe the Phase II HapMap, which characterizes over 3.1 million human single nucleotide polymorphisms (SNPs) genotyped in 270 individuals from four geographically diverse populations and includes 25-35% of common SNP variation in the populations surveyed. The map is estimated to capture untyped common variation with an average maximum r2 of between 0.9 and 0.96 depending on population. We demonstrate that the current generation of commercial genome-wide genotyping products captures common Phase II SNPs with an average maximum r2 of up to 0.8 in African and up to 0.95 in non-African populations, and that potential gains in power in association studies can be obtained through imputation. These data also reveal novel aspects of the structure of linkage disequilibrium. We show that 10-30% of pairs of individuals within a population share at least one region of extended genetic identity arising from recent ancestry and that up to 1% of all common variants are untaggable, primarily because they lie within recombination hotspots. We show that recombination rates vary systematically around genes and between genes of different function. Finally, we demonstrate increased differentiation at non-synonymous, compared to synonymous, SNPs, resulting from systematic differences in the strength or efficacy of natural selection between populations.

Genome-wide detection and characterization of positive selection in human populations.

With the advent of dense maps of human genetic variation, it is now possible to detect positive natural selection across the human genome. Here we report an analysis of over 3 million polymorphisms from the International HapMap Project Phase 2 (HapMap2). We used 'long-range haplotype' methods, which were developed to identify alleles segregating in a population that have undergone recent selection, and we also developed new methods that are based on cross-population comparisons to discover alleles that have swept to near-fixation within a population. The analysis reveals more than 300 strong candidate regions. Focusing on the strongest 22 regions, we develop a heuristic for scrutinizing these regions to identify candidate targets of selection. In a complementary analysis, we identify 26 non-synonymous, coding, single nucleotide polymorphisms showing regional evidence of positive selection. Examination of these candidates highlights three cases in which two genes in a common biological process have apparently undergone positive selection in the same population:LARGE and DMD, both related to infection by the Lassa virus, in West Africa;SLC24A5 and SLC45A2, both involved in skin pigmentation, in Europe; and EDAR and EDA2R, both involved in development of hair follicles, in Asia.

'We never thought this would be considered drug trafficking': International finance rules, policy space and Uruguay's regulation of recreational cannabis.

ABSTRACTFollowing landmark legislation in 2013, Uruguay became the first country to regulate the legal production, distribution and sale of recreational cannabis. While broader debates anticipated the significance of the UN drug conventions, the extent to which Uruguay's drug treaty obligations shaped regulation is unclear and the relevance of finance norms has been neglected. Drawing on institutionalist and governance theories, this study explores how international drug and finance regulations limited Uruguay's policy space to implement cannabis regulation, and how this was perceived by policy actors. Policy documents and 43 semi-structured interviews were thematically analysed. The analysis demonstrates how Uruguay's drug treaty obligations were less directly constraining to policy space compared to international finance norms, including the US Patriot Act, anti-money laundering standards and financial inclusion practices. Such norms exerted powerful influence over Uruguay's ability to implement aspects of cannabis supply that interact with broader financial systems, allowing banks to terminate business relationships with clients deemed as high risks for money laundering. The Uruguayan case suggests that financial regulations at diverse levels are likely to constrain policy space in other contexts where the market-based policies of cannabis regulation raise tensions with a narrowly constructed risk management principle in approaches to financial supply.

A novel microarray-based PCR assay for the detection of HSV-1, HSV-2, and VZV skin infections: A retrospective analysis.

Prevalence of HSV-1, HSV-2, and VZV infection ranges from 20% to 90%. Viral reactivation is common and results in a significant individual and socioeconomic burden. Pathognomonic skin manifestations are not always present, impairing definitive clinical diagnosis. We evaluated the performance of a novel microarray-based multiplex PCR system (Euroarray, Euroimmun Medizinische Labordiagnostika) for the molecular detection of these pathogens. In this retrospective study, 50 consecutive specimens positive for HSV-1, HSV-2, or VZV (pre-characterized by qPCR) were analyzed. Two hundred-and-five negative test results were applied as a control group. The microarray successfully detected the respective pathogens in all samples that yielded a qPCR quantifiable amount of DNA. Two and one specimens containing VZV and HSV-1 DNA beneath the limit of quantification tested microarray negative. Microarray specificity was 100%. The microarray is a useful tool for diagnosing viral infections of skin and mucous membranes, allowing rapid differentiation between three pathogens in a single assay.

Risk for Ecstasy Use Disorder and Other Substance Use Among International Users of Recreational Ecstasy/Molly/MDMA.

Ecstasy/Molly/MDMA is a widely used substance often taken in combination with other drugs in different contexts. The current study assessed ecstasy use patterns, concurrent substance use and the context of ecstasy use among an international sample of adults (N = 1,732). Participants were 87% white, 81% male, 42% college educated, 72% employed, with a mean age of 25.7 (SD = 8.3). Using the modified UNCOPE, risk for ecstasy use disorder was 22% overall, and significantly higher among younger individuals and those with greater frequency and quantity of use. Participants reporting risky ecstasy use endorsed significantly higher use of alcohol, nicotine/tobacco, cannabis, cocaine, amphetamine, benzodiazepines, and ketamine compared to those at lower risk. Great Britain (aOR = 1.86; 95% CI [1.24, 2.81]) and Nordic countries (aOR = 1.97; 95% CI [1.11, 3.47]) were approximately 2 times more likely to exhibit risk for ecstasy use disorder than the United States, Canada, Germany, and Australia/New Zealand. Taking ecstasy at home emerged as a common setting followed by electronic dance music events and music festivals. The UNCOPE may be a useful clinical tool for detecting problematic ecstasy use. Harm reduction interventions for ecstasy should target young people, substance co-administration, and context of use.

Enterovirus Central Nervous System Infection in Infancy, the Value of Routine Testing.

BACKGROUND: Human nonpolio enterovirus (EV) is a major cause of infection in neonates and infants; however, the clinical presentation and cerebrospinal fluid findings vary significantly. Infection caused by EV in patients under 1 year of age can present with a broad clinical spectrum, from fever to severe systemic and/or neurological disease. METHODS: Retrospective cohort analysis of infants with EV central nervous system (CNS) infection presenting to a tertiary center between January 2017 and December 2022. We recorded patient demographics, parent-reported symptoms at presentation, and blood and cerebrospinal fluid (CSF) testing at presentation. RESULTS: Seventy-eight patients were included in the final study. Forty-one percent of infants with an EV CNS infection had a normal CSF white blood cell count. Clinical presentation was similar in infants with and without CSF pleocytosis. Median C-reactive protein was higher in cases of EV CNS infection without pleocytosis. CONCLUSION: EV CNS infection commonly presents without CSF pleocytosis. Testing for EV should be considered in febrile infants with no source regardless of CSF parameters.

To screen or not to screen for asymptomatic bacteriuria in pregnancy: A comparative three-year retrospective review between two maternity centres.

BACKGROUND: Current national guidance in Ireland states that asymptomatic bacteriuria (AB) should be screened for at 12-16 weeks' gestation and treated with a seven-day course of antimicrobials, due to the potential risk of preterm birth and low birth weight infants (LBWI), however, this is based on low quality evidence. METHODS: Over a three-year period (2018-2020), a retrospective review was undertaken in two neighbouring maternity hospitals; one of which screens for AB (Rotunda hospital (RH)) and one which does not (National Maternity Hospital (NMH)). Patients were included on the basis of fulfilling the IDSA definition for pyelonephritis and requiring admission for intravenous antibiotics. Rates of antenatal pyelonephritis were compared between hospitals, and between screened and unscreened populations. Secondary outcomes including rates of preterm births and LBWI were compared across sites. RESULTS: A total of 47,676 deliveries between the two centres (24,768 RH; 22,908 NMH) were assessed, of which 158 patients met inclusion criteria for antenatal pyelonephritis (n = 88 RH, n = 70 NMH). There was no statistically significant difference in the rate of antenatal pyelonephritis (p = 0.34) or preterm births (p = 0.21) across sites. RH had a significantly higher rate of LBWI at 6.45% versus 5.68% of all births in NMH (p=<0.004). Given the screening rate in RH was below 100%, this cohort was further subdivided into 'RH screened' and 'RH unscreened'. There was no statistically significant difference in the rate of antenatal pyelonephritis both between the 'NMH unscreened' group (n = 70) versus the 'RH screened' group (n = 62) (p = 0.53), or in the 'RH screened' group (n = 62) versus the 'RH unscreened' group (n = 26) (p = 0.53). CONCLUSION: Omission of a screening programme for AB in NMH did not result in higher rates of antenatal pyelonephritis, preterm birth or LBWI. Our findings may inform decision-making on screening protocols and whether selective screening (i.e. screening in high-risk patients only) could be more cost-effective without compromising best quality of care.

Referral Patterns of Outpatient Palliative Care among the Head and Neck Cancer Population.

Introduction Patients with head and neck cancer (HNC) experience unique physical and psychosocial challenges that impact their health and quality of life. Early implementation of palliative care has been shown to improve various health care outcomes. Objective The aim of the present study was to evaluate the patterns of referral of patients with HNC to outpatient palliative care as they relate to utilization of resources and end-of-life discussions. Methods We performed a retrospective review of 245 patients with HNC referred to outpatient palliative care services at two Louisiana tertiary care centers from June 1, 2014, to October 1, 2019. The control group consisted of those that were referred but did not follow-up. Reasons for referral were obtained, and outcome measures such as emergency department (ED) visits, hospital readmissions, and advance care planning (ACP) documentation were assessed according to predictive variables. Results There were 177 patients in the treatment group and 68 in the control group. Patients were more likely to follow up to outpatient palliative care services if referred for pain management. Hospital system, prior inpatient palliative care, and number of outpatient visits were associated with an increased likelihood for ED visits and hospital readmissions. Those in the palliative care treatment group were also more likely to have ACP discussions. Conclusion Early implementation of outpatient palliative care among patients with HNC can initiate ACP discussions. However, there are discrepancies in referral reasons to palliative care and continued existing barriers to its effective utilization.