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In 2015, the Clinical and Laboratory Standards Institute (CLSI) updated its breakpoints for penicillin susceptibility in Corynebacterium species from <1 mg/L to <0.12 mg/L. We assessed the effect of this change on C. diphtheriae susceptibility reported at an inner city, tertiary care center in Vancouver, British Columbia, Canada, during 2015-2018 and performed whole-genome sequencing to investigate phenotypic and genotypic resistance to penicillin. We identified 44/45 isolates that were intermediately susceptible to penicillin by the 2015 breakpoint, despite meeting previous CLSI criteria for susceptibility. Sequencing did not reveal β-lactam resistance genes. Multilocus sequence typing revealed a notable predominance of sequence type 76. Overall, we saw no evidence of penicillin nonsusceptibility at the phenotypic or genotypic level in C. diphtheriae isolates from our institution. The 2015 CLSI breakpoint change could cause misclassification of penicillin susceptibility in C. diphtheriae isolates, potentially leading to suboptimal antimicrobial treatment selection. [ABSTRACT FROM AUTHOR]

Background: Adverse Drug Reactions (ADRs) are of great public health concern. FDA-approved drug labeling summarizes ADRs of a drug product mainly in three sections, i.e., Boxed Warning (BW), Warnings and Precautions (WP), and Adverse Reactions (AR), where the severity of ADRs are intended to decrease in the order of BW > WP > AR. Several reported studies have extracted ADRs from labeling documents, but most, if not all, did not discriminate the severity of the ADRs by the different labeling sections. Such a practice could overstate or underestimate the impact of certain ADRs to the public health. In this study, we applied the Medical Dictionary for Regulatory Activities (MedDRA) to drug labeling and systematically analyzed and compared the ADRs from the three labeling sections with a specific emphasis on analyzing serious ADRs presented in BW, which is of most drug safety concern. Results: This study investigated New Drug Application (NDA) labeling documents for 1164 single-ingredient drugs using Oracle Text search to extract MedDRA terms. We found that only a small portion of MedDRA Preferred Terms (PTs), 3819 out of 21,920 or 17.42%, were observed in a whole set of documents. In detail, 466/3819 (12.0%) PTs were in BW, 2023/3819 (53.0%) were in WP, and 2961/3819 (77.5%) were in AR sections. We also found a higher overlap of top 20 occurring BW PTs with WP sections compared to AR sections. Within the MedDRA System Organ Class levels, serious ADRs (sADRs) from BW were prevalent in Nervous System disorders and Vascular disorders. A Hierarchical Cluster Analysis (HCA) revealed that drugs within the same therapeutic category shared the same ADR patterns in BW (e.g., nervous system drug class is highly associated with drug abuse terms such as dependence, substance abuse, and respiratory depression). Conclusions: This study demonstrated that combining MedDRA standard terminologies with data mining techniques facilitated computer-aided ADR analysis of drug labeling. We also highlighted the importance of labeling sections that differ in seriousness and application in drug safety. Using sADRs primarily related to BW sections, we illustrated a prototype approach for computer-aided ADR monitoring and studies which can be applied to other public health documents. [ABSTRACT FROM AUTHOR]

The clinical significance of indeterminate (PCR+/Tox−) results for patients tested with a two-step algorithm for Clostridium difficile infection (CDI) is uncertain. We aimed to evaluate the clinical presentation and 8-week outcomes of patients with indeterminate test results. Patients with stool samples testing positive by PCR and negative by toxin A/B immunoassay between February 1, 2017, and April 30, 2018, were assessed by antimicrobial stewardship program (ASP) clinicians and classified as colonized or infected. Retrospective chart review was performed to obtain outcomes occurring within 8 weeks of testing, including recurrent C. difficile diarrhea, subsequent treatment for CDI, follow-up C. difficile testing, all-cause mortality, and CDI-related complications. In total, 110 PCR+/Tox− patients were evaluated. ASP classified 54% of patients as infected and 46% as colonized. Patients assessed and classified as colonized did not have increased adverse outcomes by 8 weeks compared to those assessed as infected, despite not receiving treatment for CDI. We conclude that PCR+/Tox− patients are heterogeneous with respect to clinical presentation. Negative toxin A/B immunoassay in a two-step algorithm should not be interpreted in isolation to distinguish colonization from infection as many PCR+/Tox− results may be clinically significant for CDI. [ABSTRACT FROM AUTHOR]

A Spanish group recently reported that four patients with chronic inflammatory demyelinating polyneuropathy carrying IgG4 autoantibodies against contactin 1 showed aggressive symptom onset and poor response to intravenous immunoglobulin. We aimed to describe the clinical and serological features of Japanese chronic inflammatory demyelinating polyneuropathy patients displaying the anti-contactin 1 antibodies. Thirteen of 533 (2.4%) patients with chronic inflammatory demyelinating polyneuropathy had anti-contactin 1 IgG4 whereas neither patients from disease or normal control subjects did (P = 0.02). Three of 13 (23%) patients showed subacute symptom onset, but all of the patients presented with sensory ataxia. Six of 10 (60%) anti-contactin 1 antibody-positive patients had poor response to intravenous immunoglobulin, whereas 8 of 11 (73%) antibody-positive patients had good response to corticosteroids. Anti-contactin 1 IgG4 antibodies are a possible biomarker to guide treatment option. [ABSTRACT FROM AUTHOR]

Background: Few studies have evaluated opioid consumption after various inpatient surgical procedures., Objectives: To describe opioid prescription patterns and to characterize patient-reported use of opioids after surgery., Methods: This single-centre prospective observational study was conducted between February and October 2021 at the Jewish General Hospital in Montréal, Quebec. Patients 18 years of age or older who underwent a surgical procedure, were hospitalized for 24 hours or longer after the procedure, and had an opioid prescription at the time of discharge were included. Data were collected for the quantity of opioids prescribed, as documented in hospital records, and the quantity consumed, as reported by participants. Various potential predictors of opioid consumption were explored, and data were also collected on patients' use of non-opioid coanalgesia, scores on the Numeric Rating Scale for pain, opioid renewal requests, and proper opioid disposal during the 30-day follow-up period., Results: A total of 150 participants completed the study. The median dose prescribed was 10 opioid pills (75.0 morphine milligram equivalents). By the end of the follow-up period, a median of 1 pill (7.5 morphine milligram equivalents) had been consumed from the total amount in the discharge prescription. Overall, 66 participants (44.0%) did not consume any of the opioids prescribed at discharge. Of the total number of pills prescribed, 58.2% (1193/2050) were unused, and 7.0% (5/71) of participants with unused pills disposed of them properly., Conclusions: Following discharge from hospital, postoperative patients consumed a median proportion of only 10% of prescribed opioid pills. More than half of all prescribed pills were unused. Protocols implementing specific prescribing strategies warrant further investigation to evaluate their potential impact on opioid prescription and consumption., Competing Interests: Competing interests: For activities unrelated to the study reported here, David Williamson serves on a data safety monitoring board for a University of Ottawa study of dexmedetomidine in agitated delirium, and Vincent Dagenais-Beaulé has received consulting fees from Otsuka-Lundbeck, Abbvie, and the Institut national d’excellence en santé et services sociaux (INESSS); speaker’s honoraria from Otsuka-Lundbeck, HLS Therapeutics, and Abbvie; and support for meeting attendance from Otsuka-Lundbeck. No other competing interests were declared., (2024 Canadian Society of Hospital Pharmacists. All content in the Canadian Journal of Hospital Pharmacy is copyrighted by the Canadian Society of Hospital Pharmacy. In submitting their manuscripts, the authors transfer, assign, and otherwise convey all copyright ownership to CSHP.)

Logged and disturbed forests are often viewed as degraded and depauperate environments compared with primary forest. However, they are dynamic ecosystems 1 that provide refugia for large amounts of biodiversity 2,3 , so we cannot afford to underestimate their conservation value 4 . Here we present empirically defined thresholds for categorizing the conservation value of logged forests, using one of the most comprehensive assessments of taxon responses to habitat degradation in any tropical forest environment. We analysed the impact of logging intensity on the individual occurrence patterns of 1,681 taxa belonging to 86 taxonomic orders and 126 functional groups in Sabah, Malaysia. Our results demonstrate the existence of two conservation-relevant thresholds. First, lightly logged forests (<29% biomass removal) retain high conservation value and a largely intact functional composition, and are therefore likely to recover their pre-logging values if allowed to undergo natural regeneration. Second, the most extreme impacts occur in heavily degraded forests with more than two-thirds (>68%) of their biomass removed, and these are likely to require more expensive measures to recover their biodiversity value. Overall, our data confirm that primary forests are irreplaceable 5 , but they also reinforce the message that logged forests retain considerable conservation value that should not be overlooked., (© 2024. The Author(s).)

Poor oral health is a growing concern among older populations. It is often caused by a failure to maintain proper oral hygiene and inaccessible dental care. Poor oral health in older individuals in long-term care institutions (LTCIs) can be attributed to the fact that healthcare workers might be poorly trained in oral care assessment and practice. To address this issue, an assessment tool has been developed and validated to guide and evaluate healthcare workers' oral care practices, ensuring the delivery of adequate care and early detection of dental diseases in LTCIs. The tool includes an oral health assessment and an assessment of oral care procedures. It was developed following a robust literature review, two stages of expert reviews, content validity checks, and a pilot study. A total of twenty-three items were developed and validated, with seven items related to oral health assessment and sixteen related to oral care procedures. The items were assessed for content validity and relevance, with high values of 1 obtained for all Item-level Content Validity Index (I-CVI), Scale-level Content Validity Index (S-CVI), and S-CVI/Universal Agreement (UA) scores. This indicates a high level of agreement among the experts ( n = 12) regarding the relevance and importance of the items. A pilot study involving 20 nursing students confirmed the tool's reliability, applicability, and feasibility, demonstrating its high appropriateness and applicability. The newly developed and validated assessment tool can effectively guide and evaluate healthcare workers' oral care practices, enhancing their competence and improving the oral health of older residents.

Pharmaceutical sector corruption undermines patient access to medicines by diverting public funds for private gain and exacerbating health inequities . This paper presents an analysis of UN Convention Against Corruption (UNCAC) compliance in seven countries and examines how full UNCAC adoption may reduce corruption risks within four key pharmaceutical decision-making points: product approval, formulary selection, procurement, and dispensing. Countries were selected based on their participation in the Medicines Transparency Alliance and the WHO Good Governance for Medicines Programme. Each country's domestic anti-corruption laws and policies were catalogued and analysed to evaluate their implementation of select UNCAC Articles relevant to the pharmaceutical sector. Countries displayed high compliance with UNCAC provisions on procurement and the recognition of most public sector corruption offences. However, several countries do not penalise private sector bribery or provide statutory protection to whistleblowers or witnesses in corruption proceedings, suggesting that private sector pharmaceutical dispensing may be a decision-making point particularly vulnerable to corruption. Fully implementing the UNCAC is a meaningful first step that countries can take reduce pharmaceutical sector corruption. However, without broader commitment to cultures of transparency and institutional integrity, corruption legislation alone is likely insufficient to ensure long-term, sustainable pharmaceutical sector good governance.

Throughout the COVID-19 pandemic, international access to COVID-19 vaccines and other health technologies has remained highly asymmetric. This inequity has had a particularly deleterious impact on low- and middle-income countries, engaging concerns about the human rights to health and to the equal enjoyment of the benefits of scientific progress enshrined under articles 12 and 15 of the International Covenant on Economic, Social and Cultural Rights. In response, the relationship between intellectual property rights and public health has reemerged as a subject of global interest. In October 2020, a wholesale waiver of the copyright, patent, industrial design, and undisclosed information sections of the Agreement on Trade-Related Aspects of Intellectual Property (TRIPS Agreement) was proposed by India and South Africa as a legal mechanism to increase access to affordable COVID-19 medical products. Here, we identify and evaluate the TRIPS waiver positions of World Trade Organization (WTO) members and other key stakeholders throughout the waiver's 20-month period of negotiation at the WTO. In doing so, we find that most stakeholders declined to explicitly contextualize the TRIPS waiver within the human right to health and that historical stakeholder divisions on the relationship between intellectual property and access to medicines appear largely unchanged since the early 2000s HIV/AIDS crisis. Given the WTO's consensus-based decision-making process, this illuminates key challenges faced by policy makers seeking to leverage the international trading system to improve equitable access to health technologies., Competing Interests: Competing interests: None declared., (Copyright © 2022 Kohler, Wong, and Tailor.)

Epstein-Barr virus (EBV) is associated with a diverse range of tumors of both lymphoid and epithelial origin. Similar to other herpesviruses, EBV displays a bipartite life cycle consisting of latent and lytic phases. Current dogma indicates that the latent genes are key drivers in the pathogenesis of EBV-associated cancers, while the lytic genes are primarily responsible for viral transmission. In recent years, evidence has emerged to show that the EBV lytic phase also plays an important role in EBV tumorigenesis, and the expression of EBV lytic genes is frequently detected in tumor tissues and cell lines. The advent of next generation sequencing has allowed the comprehensive profiling of EBV gene expression, and this has revealed the consistent expression of several lytic genes across various types of EBV-associated cancers. In this review, we provide an overview of the functional implications of EBV lytic gene expression to the oncogenic process and discuss possible avenues for future investigations.

Competing Interests: Competing interests: During the conduct of the study: KP reports grants from Unitaid; VW reports grants from the Center for Emerging Infectious Diseases Policy & Research, Gilead, UCB, the Fleming Fund, the World Health Organization Southeast Asia Office, the Rockefeller Brothers Foundation, the United States Pharmacopeia, Management Sciences for Health and the National Institute for Allergy and Infectious Diseases; and JK reports grants from the Leslie Dan Faculty of Pharmacy, University of Toronto CSAP Award and the Connaught Global Challenge Award from the University of Toronto. AW and VR have nothing to disclose. The funders had no role in the conception, analysis or writing of this analysis.

Background: Research has highlighted that satisfaction in health, and instrumental support (IS) are key areas of life affecting an individual's wellbeing. Many social and public health initiatives use these two intervention mechanisms to improve individual's wellbeing. For the purpose of cost-benefit assessment, there has been growing interest in expressing these intervention effects in economic terms. However, only a handful of studies have ever estimated these effects in economic terms, none of which examined them in a Chinese context. The aim of this study is to extend this line of valuation work to the Chinese population, estimating the implicit willingness-to-pays on the effects of improving individuals' self-rated health (SRH) status and IS on their life satisfaction (LS)., Methods: Using data from a two-wave representative panel survey in Hong Kong (n = 1,109), this study conducted a cross-lagged analysis with a structural equation modelling technique to examine the causal effects of SRH and IS on LS. The use of this cross-lagged approach was an effort to minimise the endogeneity problem. Then, substituting the respective estimates to the formulae of compensating surplus, the marginal rate of substitution of SRH and IS with respect to individual's equivalised monthly household income (HI) were estimated and were then expressed as the implicit willingness-to-pays on the effect of improving individuals' SRH and IS on their LS., Results: The cross-lagged analysis ascertained the causal effects of SRH (β = 0.074, 95% Confidence Interval: 0.021, 0.127) and IS (β = 0.107, 95% Confidence Interval: 0.042, 0.171) on individuals' satisfaction with life. Translating into the concept of compensating surplus, the implicit monetary values of improving the sample's SRH from "poor health" to "excellent health" and their perceived IS from "little support" to "a lot of support" are equivalent to an increase in their equivalised monthly HI by US$1,536 and US$1,523 respectively., Conclusions: This study is the first to derive the implicit monetary values of SRH and IS on individual's LS in a predominantly Chinese society, and it has implications for the cost-benefit assessment in wellbeing initiatives within the population., (© 2022. The Author(s).)

Background: Suicide is one of the leading causes of death in children and youth. Using a sample of fatal suicides among school-aged students in Hong Kong, this study aimed to demonstrate how the classification of children and adolescent suicides into distinct subgroups using cluster analysis can alert us to the heterogeneous nature of the student suicide population and increase our understanding of multidimensional underlying causes.  METHODS: Deaths by suicide of Hong Kong primary and secondary school students occurring between 2013-16 were identified. Reports were acquired from the Coroner's Court, Police Force, and Education Bureau in Hong Kong. Information about students' sociodemographic characteristics, suicide circumstances, stressors, and risk factors was extracted and organized for analysis. Based on the indicated stressors (school, family, close relationship, social challenge, finance, risk behaviour, suicide exposure, others) and risk factors (health and mental health, history of self-harm, suicidality, and psychological maladjustment), cluster analysis was conducted to derive distinct profiles of student suicides., Results: A four-cluster solution was found. Patterns of stressors, risk factors, background characteristics and suicide circumstances within each cluster were examined. Four distinct and meaningful profiles of student suicides were characterised as "school distress", "hidden", "family and relationship", and "numerous issues"., Conclusions: Findings highlighted the need to approach student suicides in meaningfully differentiated ways. Gathering suicide report data and generating evidence that advances our knowledge of student suicide profiles are important steps towards early identification and intervention., (© 2022. The Author(s).)

Transnational ivory traffickers continue to smuggle large shipments of elephant ivory out of Africa, yet prosecutions and convictions remain few. We identify trafficking networks on the basis of genetic matching of tusks from the same individual or close relatives in separate shipments. Analyses are drawn from 4,320 savannah (Loxodonta africana) and forest (L. cyclotis) elephant tusks, sampled from 49 large ivory seizures totalling 111 t, shipped out of Africa between 2002 and 2019. Network analyses reveal a repeating pattern wherein tusks from the same individual or close relatives are found in separate seizures that were containerized in, and transited through, common African ports. Results suggest that individual traffickers are exporting dozens of shipments, with considerable connectivity between traffickers operating in different ports. These tools provide a framework to combine evidence from multiple investigations, strengthen prosecutions and support indictment and prosecution of transnational ivory traffickers for the totality of their crimes., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Research suggests that a whole-school approach to mental health promotion can be more effective than a compartmentalized approach. In particular, student-led initiatives have demonstrated a positive impact on students' mental health, though not without systemic and individual barriers. Factors that lead to successful implementation and sustaining of student-led initiatives are currently not well understood., Methods: A case study is presented to demonstrate how a student-led intervention came about, inspired changes in the school organization and members, and transformed the school's approach to mental health promotion. Analysis of in-depth interviews with student leaders and adult advisors was informed by theories of innovation diffusion and human motivation., Results: Key factors and mechanisms of change were identified for the initiation, transformation, and institutionalization stages of the student-led initiative. Changes in students' identity and adult advisors' mindset were found to be integral to the successful conversion to a whole-school approach in mental health promotion., Conclusions: This study confirms the value of mobilizing the student body as an active resource in promoting mental health in school and the importance of input from school management, advisors, and intervention expert. Recommendations on how to implement a student-led initiative and sustain the positive changes are given., (© 2021 American School Health Association.)

Background: Transparency and accountability are essential components at all stages of the trade negotiation process. This study evaluates the extent to which these principles were upheld in the United States' public consultation process during the negotiation of the United States-Mexico-Canada Agreement (USMCA), with respect to public comments about the pharmaceutical sector and access to medicines., Results: The public consultation process occurred before the start of official negotiations and was overseen by the Office of the United States Trade Representative (USTR). It included both written comments and oral testimony about US trade negotiation objectives. Of the written comments that specifically discussed issues relating to pharmaceuticals, the majority were submitted by private individuals, members of the pharmaceutical industry, and civil society organizations. Nearly all comments submitted by non-industry groups indicated that access to medicines was a priority issue in the renegotiated agreement, with specific reference to price affordability. By contrast, more than 50% of submissions received from members or affiliates of the pharmaceutical industry advocated for strengthened pharmaceutical intellectual property rights, greater regulatory data protections, or both. This study reveals mixed outcomes with respect to the level of transparency achieved in the US trade negotiation process. Though input from the public at-large was actively solicited, the extent to which these comments were considered in the content of the final agreement is unclear. A preliminary comparison of the analyzed comments with the USTR's final negotiating objectives and the final text of the USMCA shows that several provisions that were advanced exclusively by the pharmaceutical industry and ultimately adopted in the final agreement were opposed by the majority of non-industry stakeholders., Conclusions: Negotiators could increase public transparency when choosing to advance one competing trade objective over another by actively providing the public with clear rationales for their negotiation positions, as well as details on how public comments are taken into account to form these rationales. Without greater clarity on these aspects, the public consultation process risks appearing to serve as a cursory government mechanism, lacking in accountability and undermining public trust in both the trade negotiation process and its outcomes., (© 2021. The Author(s).)

Background: Schools are a key setting for student well-being promotion. Various school-based mental health programs have been implemented worldwide, with greater emphasis placed on psychological and social aspects. The bio-psycho-social model provides a holistic and integrated view of mental health based on theory and research evidence. Given the importance of considering all three dimensions in mental health promotion, this study explored reasons for the relative neglect of this approach by studying the early phase of school well-being program development and implementation. Method: In total, 77 Hong Kong government-funded student well-being programs implemented in 2000-2009 were reviewed for the use of biological, psychological, and social interventions. Questionnaires and interviews were conducted to explore program leaders' usage and views regarding theoretical frameworks and evidence-based practice and program evaluation. Challenges encountered in the initial stage of school well-being program development and implementation were identified and analyzed. Results: Of the 77 programs reviewed, only 5 addressed all three bio-psycho-social factors of mental health. A significantly greater number of programs addressed psychological ( n = 63) and social ( n = 40) factors compared to those that covered biological factors of mental health ( n = 13). Of 24 program implementers who responded to the online survey, 75% claimed to have studied or applied a theoretical framework yet only 41.7% considered evidence-based practices to be important. The majority of interviewed participants valued their own practical experience over theory and research evidence. Many programs lacked rigorous evaluation of clear objectives and measurable outcomes, thus the mechanisms of change and program effectiveness were uncertain. Perceived barriers to program adoption and continuation were identified. Conclusion: This study highlighted a neglect of the biological contribution to mental health in school well-being promotion initiatives, possibly due to lack of theoretical knowledge and evidence-based practice among program leaders and implementers in the early phase of school mental health promotion. The bio-psycho-social model should therefore be recommended for student well-being programs as a holistic and integrated theory of mental health underpinning program objectives, mechanisms of change, and measurable outcomes. To develop effective practices in student well-being promotion, more thorough documentation, a rigorous evaluation framework, and support for frontline educators to evaluate their practices were recommended., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wong, Chan, Tsang, Chan, Shum, Lai and Yip.)

Rationale: There is a need to develop imaging protocols which assess neutrophilic inflammation in the lung., Aim: To quantify whole lung neutrophil accumulation in (1) healthy volunteers (HV) following inhaled lipopolysaccharide (LPS) or saline and (2) patients with COPD using radiolabelled autologous neutrophils and single-photon emission computed tomography/CT (SPECT/CT)., Methods: 20 patients with COPD (Global initiative for chronic obstructive lung disease (GOLD) stages 2-3) and 18 HVs were studied. HVs received inhaled saline (n=6) or LPS (50 µg, n=12) prior to the injection of radiolabelled cells. Neutrophils were isolated using dextran sedimentation and Percoll plasma gradients and labelled with 99m Technetium (Tc)-hexamethylpropyleneamine oxime. SPECT was performed over the thorax/upper abdomen at 45 min, 2 hours, 4 hours and 6 hours. Circulating biomarkers were measured prechallenge and post challenge. Blood neutrophil clearance in the lung was determined using Patlak-Rutland graphical analysis., Results: There was increased accumulation of 99m Tc-neutrophils in the lungs of patients with COPD and LPS-challenged subjects compared with saline-challenged subjects (saline: 0.0006±0.0003 mL/min/mL lung blood distribution volume [mean ±1 SD]; COPD: 0.0022±0.0010 mL/min/mL [p<0.001]; LPS: 0.0025±0.0008 mL/min/mL [p<0.001]). The accumulation of labelled neutrophils in 10 patients with COPD who underwent repeat radiolabelling/imaging 7-10 days later was highly reproducible (0.0022±0.0010 mL/min/mL vs 0.0023±0.0009 mL/min/mL). Baseline interleukin (IL)-6 levels in patients with COPD were elevated compared with HVs (1.5±1.06 pg/mL [mean ±1 SD] vs 0.4±0.24 pg/mL). LPS challenge increased the circulating IL-6 levels (7.5±2.72 pg/mL) 9 hours post challenge., Conclusions: This study shows the ability to quantify 'whole lung' neutrophil accumulation in HVs following LPS inhalation and in subjects with COPD using autologous radiolabelled neutrophils and SPECT/CT imaging. Moreover, the reproducibility observed supports the feasibility of using this approach to determine the efficacy of therapeutic agents aimed at altering neutrophil migration to the lungs., Competing Interests: Competing interests: MB, AC, KP, SM, JM, ML, GB, EJ, MdG, FW and EMH are employees of GSK. NT, NF, RS, DG, CS, AW, JB, AMP and ERC have no competing interests to declare., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research, established by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks, a public-private partnership with the US Food and Drug Administration, convened a second meeting of sedation experts from a variety of clinical specialties and research backgrounds to develop recommendations for procedural sedation research. The previous meeting addressed efficacy and patient- and/or family-centered outcomes. This meeting addressed issues of safety, which was defined as "the avoidance of physical or psychological harm." A literature review identified 133 articles addressing safety measures in procedural sedation clinical trials. After basic reporting of vital signs, the most commonly measured safety parameter was oxygen saturation. Adverse events were inconsistently defined throughout the studies. Only 6 of the 133 studies used a previously validated measure of safety. The meeting identified methodological problems associated with measuring infrequent adverse events. With a consensus discussion, a set of core and supplemental measures were recommended to code for safety in future procedural clinical trials. When adopted, these measures should improve the integration of safety data across studies and facilitate comparisons in systematic reviews and meta-analyses.

Background: Daily bathing with chlorhexidine gluconate (CHG) is increasingly used in intensive care units to prevent hospital-associated infections, but limited evidence exists for noncritical care settings., Methods: A prospective crossover study was conducted on 4 medical inpatient units in an urban, academic Canadian hospital from May 1, 2014-August 10, 2015. Intervention units used CHG over a 7-month period, including a 1-month wash-in phase, while control units used nonmedicated soap and water bathing. Rates of hospital-associated methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) colonization or infection were the primary end point. Hospital-associated S. aureus were investigated for CHG resistance with a qacA/B and smr polymerase chain reaction (PCR) and agar dilution., Results: Compliance with daily CHG bathing was 58%. Hospital-associated MRSA and VRE was decreased by 55% (5.1 vs 11.4 cases per 10,000 inpatient days, P = .04) and 36% (23.2 vs 36.0 cases per 10,000 inpatient days, P = .03), respectively, compared with control cohorts. There was no significant difference in rates of hospital-associated Clostridium difficile. Chlorhexidine resistance testing identified 1 isolate with an elevated minimum inhibitory concentration (8 µg/mL), but it was PCR negative., Conclusions: This prospective pragmatic study to assess daily bathing for CHG on inpatient medical units was effective in reducing hospital-associated MRSA and VRE. A critical component of CHG bathing on medical units is sustained and appropriate application, which can be a challenge to accurately assess and needs to be considered before systematic implementation., (Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: Sialylation in Fc portion of IgG plays a crucial role in the pathogenesis of autoimmune diseases and the working mechanism of intravenous immunoglobulin (IVIG). We aim to test whether IgG-Fc sialylation is a biomarker of disease activity for chronic inflammatory demyelinating polyneuropathy (CIDP)., Methods: By using specific lectins for sialylation, galactosylation and agalactosylation, lectin-enzyme assay and lectin blotting with pretreatment of IgG degradating enzyme of Streptococcus pyogenes were performed to compare the glycosylation levels of serum IgG-Fc (1) between patients of untreated CIDP (n=107) and normal control subjects (n=27), (2) among patients with untreated CIDP of different clinical severities and (3) before and after IVIG treatment of patients with CIDP (n=12)., Results: Sialylation and galactosylation of IgG-Fc were significantly reduced in patients with CIDP than normal control subjects (p=0.003 and 0.033, respectively), whereas agalactosylation was increased in CIDP (p=0.21). Ratios of sialylated/agalactosylated IgG-Fc levels were significantly reduced in CIDP (p<0.001) and inversely related to disease severity (p=0.044). After IVIG treatment, levels of sialylated IgG-Fc significantly increased (p=0.003)., Conclusions: Sialylation of IgG-Fc is reduced in CIDP. Its level correlated with clinical severity and increased after IVIG treatment. Sialylated as well as ratio of sialylated/agalactosylated IgG-Fc could be new measures to monitor the disease severity and treatment status in CIDP., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Because of the limitation of on-site neurology workforce, telestroke was implemented to overcome this barrier. We explored the efficacy and safety of intravenous (IV) stroke thrombolysis service by telestroke when neurologist was not available on-site., Methods: From January 2009 to December 2012, we compared patients treated with IV stroke thrombolysis by telestroke in the form of telephone consultation with teleradiology, to patients treated after in-person assessment by the same team of neurologists in a regional hospital. Door-to-needle time, symptomatic intracranial hemorrhage, and functional outcome at 3 months were prospectively collected and compared between the groups., Results: In all, 152 patients were treated with IV thrombolysis; 102 patients were treated with neurologist on-site; whereas 50 patients were treated by internists with telestroke. Fifty-two percent of the telemedical group achieved excellent outcome compared to 43% of the neurologist on-site group (P = .30). Symptomatic intracranial hemorrhage rate (4.0% versus 4.9%, P = 1.0) and mortality (8.3% versus 11.9%, P = .49) were comparable. Using the multiple logistic regression analysis, age, baseline stroke severity, and extent of early ischemic change on brain computed tomography scan, are independent predictors for excellent outcome, whereas the presence of neurologist on-site is not correlated with the outcome., Conclusions: Patients treated without neurologist on-site achieved similar outcome. Telephone consultation and teleradiology-guided IV stroke thrombolysis, with the support of on-site internist appeared safe and efficacious., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate the use of intravenous immunoglobulin (IVIG) in preventing relapses in patients with neuromyelitis optica (NMO) and its spectrum disorders (NMOSDs)., Methods: Six NMO/NMOSD patients who were treated with IVIG induction dose followed by 2- to 3- monthly infusions were retrospectively identified. Annualized relapse rates (ARR) and Expanded Disability Status Scale (EDSS) pre- and post-IVIG were recorded., Results: Median number of relapses and median ARR significantly reduced from 8.0 to 1.0 and 0.75 to 0.15 (p<0.05) respectively. Median EDSS of 6.5 remained the same. Median duration of treatment was 4.0 years., Conclusion: IVIG may be used to reduce the relapse frequency in patients with NMO/NMOSD., (Copyright © 2015 Elsevier B.V. All rights reserved.)

We present a case of a 70-year-old HIV negative man with a five-year history of progressive dysnomia and new onset right extremity numbness, dysarthria, and blurry vision. On magnetic resonance imaging (MRI), an infiltrative enhancing tumor was noted. Follow up brain biopsy results revealed a small lymphocytic infiltrate with scattered plasma cells in a predominantly perivascular growth pattern. Flow-cytometric findings revealed a lambda monotypic B-cell population. The morphology and the flow cytometric findings were consistent with involvement by a low grade B-cell lymphoma. Subsequent positron emission tomography (PET) studies along with bone marrow biopsy and serum protein electrophoresis showed no evidence of systemic disease. The above findings are consistent with involvement by a non-dural extranodal marginal zone B-cell lymphoma (MZBCL) primary to the central nervous system (CNS). This is the first reported case of a primary CNS MZBCL with flow cytometric analysis. A review of literature on this rare entity is also included.