An observational study of system-level changes to improve the recording of very brief advice for smoking cessation in an inpatient mental health setting.

BACKGROUND: Smoking prevalence among people with psychosis remains high. Providing Very Brief Advice (VBA) comprising: i) ASK, identifying a patient's smoking status ii) ADVISE, advising on the best way to stop and iii) ACT (OFFER), offering a referral to specialist smoking cessation support, increases quit attempts in the general population. We assessed whether system-level changes in a UK mental health organisation improved the recording of the provision of ASK, ADVISE, ACT (OFFER) and consent to referral to specialist smoking cessation support (ACT (CONSENT)). METHODS: We conducted a study using a regression discontinuity design in four psychiatric hospitals with patients who received treatment from an inpatient psychosis service over 52 months (May 2012-September 2016). The system-level changes to facilitate the provision of VBA comprised: A) financially incentivising recording smoking status and offer of support (ASK and ACT (OFFER)); B) introduction of a comprehensive smoke-free policy; C) enhancements to the patient electronic healthcare record (EHCR) which included C1) a temporary form to record the financial incentivisation of ASK and ACT (OFFER) C2) amendments to how VBA was recorded in the EHCR and C3) the integration of a new electronic national referral system in the EHCR. The recording of ASK, ADVISE, ACT (OFFER/CONSENT) were extracted using a de-identified psychiatric case register. RESULTS: There were 8976 admissions of 5434 unique individuals during the study period. Following A) financial incentive, the odds of recording ASK increased (OR: 1.56, 95%CI: 1.24-1.95). Following B) comprehensive smoke-free policy, the odds of recording ADVICE increased (OR: 3.36, 95%CI: 1.39-8.13). Following C1) temporary recording form, the odds of recording ASK (OR:1.99, 95%CI:1.59-2.48) and recording ACT (OFFER) increased (OR: 4.22, 95%CI: 2.51-7.12). Following C3) electronic referral system, the odds of recording ASK (OR:1.79, 95%CI: 1.31-2.43) and ACT (OFFER; OR: 1.09, 95%CI: 0.59-1.99) increased. There was no change in recording VBA outcomes following C2) amendments to VBA recording. CONCLUSIONS: Financial incentives and the recording of incentivised outcomes, the comprehensive smoke-free policy, and the electronic referral system, were associated with increases in recording individual VBA elements, but other changes to the EHCR were not. System-level changes may facilitate staff recording of VBA provision in mental health settings.

Fidaxomicin Compared With Oral Vancomycin for the Treatment of Severe Clostridium difficile-Associated Diarrhea: A Retrospective Review.

Purpose: The most recent published guidelines on Clostridium difficile-associated diarrhea (CDAD) developed by the Infectious Diseases Society of America (IDSA) were released in 2017 and outline its treatment based on severity of the disease and recurrence; however, a clear first-line agent has not been recommended specifically for severe CDAD. Methods: This retrospective chart review was approved by the institutional review board and consisted of three community hospitals and one academic medical center. To be included, patients need to meet criteria for severe CDAD and receive at least 72 hours of therapy. Patients received either oral vancomycin or fidaxomicin, in addition to other therapies for CDAD, and differences in outcomes such as cost obtained from a common charge center, rates of recurrence, time to recurrence as measured at time of positive to negative polymerase chain reaction (PCR) test, and mortality were assessed. Results: Of the 147 patients, 74 patients received fidaxomicin and 73 patients received oral vancomycin. The average hospitalization cost for patients receiving fidaxomicin was $129,338.69 and for patients receiving vancomycin was $153,563.81 (P = .26). Recurrence rates were lower with fidaxomicin compared with vancomycin (6.8% vs 17.6%; P = .047), and time to recurrence was longer with fidaxomicin versus vancomycin, but not statistically significant (96.8 ± 45.9 days vs 63.2 ± 66.9 days; P = .321). Mortality, length of stay in the intensive care unit, and overall length of stay were similar between the two therapies. Conclusions: In the treatment of severe CDAD, recurrence rates were lower and time to recurrence was higher with fidaxomicin compared with oral vancomycin. A clear financial benefit has yet to translate from these known findings.

Probing the Effects of Pyrimidine Functional Group Switches on Acyclic Fleximer Analogues for Antiviral Activity.

Due to their ability to inhibit viral DNA or RNA replication, nucleoside analogues have been used for decades as potent antiviral therapeutics. However, one of the major limitations of nucleoside analogues is the development of antiviral resistance. In that regard, flexible nucleoside analogues known as "fleximers" have garnered attention over the years due to their ability to survey different amino acids in enzyme binding sites, thus overcoming the potential development of antiviral resistance. Acyclic fleximers have previously demonstrated antiviral activity against numerous viruses including Middle East Respiratory Syndrome coronavirus (MERS-CoV), Ebola virus (EBOV), and, most recently, flaviviruses such as Dengue (DENV) and Yellow Fever Virus (YFV). Due to these interesting results, a Structure Activity Relationship (SAR) study was pursued in order to analyze the effect of the pyrimidine functional group and acyl protecting group on antiviral activity, cytotoxicity, and conformation. The results of those studies are presented herein.

Flex-nucleoside analogues - Novel therapeutics against filoviruses.

Fleximers, a novel type of flexible nucleoside that have garnered attention due to their unprecedented activity against human coronaviruses, have now exhibited highly promising levels of activity against filoviruses. The Flex-nucleoside was the most potent against recombinant Ebola virus in Huh7 cells with an EC50=2µM, while the McGuigan prodrug was most active against Sudan virus-infected HeLa cells with an EC50 of 7µM.

Time to Smoke: Facilitating Smoking Breaks in Mental Health Inpatient Settings.

INTRODUCTION: Prevalence of smoking in mental health patients is up to three times higher than in the general population, with the highest rates seen in inpatient settings. In many countries, smoke-free policies in inpatient settings prohibit smoking in buildings but allow supervised smoking breaks. We aimed to estimate staff resources dedicated to such breaks. METHODS: A cross sectional survey was conducted with a convenience sample of inpatient mental health staff from four hospitals in London, England. Staff were asked about the number of designated supervised smoking breaks and their duration, per day, on their ward. We calculated the opportunity cost of the time allocated to supervising smoking. RESULTS: The survey was completed by 67 staff from 25 inpatient wards across four hospital sites. Eighteen wards had designated daily supervised smoking breaks; the average number of breaks per ward was 7.6 (SD 3.9), with an average of 2 hours, 23 minutes a day of clinical time dedicated to supervising smoking. We estimated the opportunity cost of supervising smoking was between £50 to £238 per ward per day or £18 250 to £86 870 per ward per year, depending on the seniority of staff supervising smoking breaks. CONCLUSIONS: Considerable time and resources is being used to facilitate smoking in mental health hospitals with smoke-free policies which allow smoking in hospital grounds. This resource could be redirected to provide evidence-based care that improves health and wellbeing, such as tobacco dependence treatment. IMPLICATIONS: This study is the first to estimate the time and opportunity costs of facilitating smoking across different wards in a mental health setting in the United Kingdom. Health care resources are scarce, including staff time. Every time staff facilitate smoking, clinical time is diverted away from therapeutic activities that contribute to improved patient health. Rather than suggesting any financial savings can be made through the introduction of smoke-free services, we present one metric of the value to mental health service providers of the hours of clinical time that could be released to provide therapeutic care.

Tinospora Cordifolia: A review of its immunomodulatory properties.

Emergent health threats have heightened human awareness of the need for health and wellness measures that promote resilience to disease. In addition to proper nutrition and exercise, health-conscious consumers are seeking natural-based modalities, e.g. botanical preparations, that positively impact the immune system. In Ayurvedic ethnomedicine, Tinospora cordifolia (T. cordifolia), a deciduous climbing shrub indigenous to India, has been used to historically to combat acute and chronic inflammation as well as to promote a balanced immune response. As a dietary supplement, T. cordifolia has been administered most often as a decoction either alone or in compositions containing other medicinal plant extracts of the Terminalia and Phyllanthus species. Extensive phytochemical characterization of aqueous and alcoholic extracts of different Tinospora species has identified over two hundred different phytochemicals from non-overlapping chemical classes with the most abundant being diterpenoids containing the clerodane-type skeleton. Numerous pharmacology studies have demonstrated that T. cordifolia modulates key signaling pathways related to cell proliferation, inflammation, and immunomodulation. However, rigorous dereplication studies to identify active constituents in various T. cordifolia extracts and their fractions are lacking. In this review, we will summarize the current information regarding T. cordifolia's ethnomedicinal uses, phytochemistry, pharmacological activities, and safety in order to highlight its potential as an immunomodulatory dietary supplement.

Smoking-related violence in a mental health setting following the implementation of a comprehensive smoke-free policy: A content analysis of incident reports.

Smoke-free policies in mental health settings are important to protect health but are often impeded by staff concerns that physical violence may increase. We aimed to address the literature gap about the frequency, nature, and management of physical violence in relation to smoking. We compared the antecedents and containment of smoking-related incidents of physical violence over a two-year period, (12 months when an indoor-only smoke-free policy was in place, followed by 12 months after a new comprehensive smoke-free policy was introduced) using incident reports completed by staff in a large mental health organization in London, UK. Sixty-one smoking-related incidents occurred during the indoor-only smoke-free policy period; 32 smoking-related incidents occurred during the comprehensive smoke-free policy. We identified four antecedent categories for physical violence: i) patient request to smoke denied by staff; ii) during a supervised smoking break; iii) staff response to a patient breach of the smoke-free policy iv) asking for, trading or stealing smoking materials. The antecedent pattern changed across the two policy periods, with fewer incidents of denying a patient's request to smoke and a greater number of incidents involving staff responding to breaches occurring after the introduction of the comprehensive smoke-free policy. The prohibition of smoking breaks removed this source of violence. Timeout and PRN medication were the most common containment interventions. Understanding the context of smoking-related violence may inform clinical guidelines about its prevention and management.

Fire Incidents in a Mental Health Setting: Effects of Implementing Smokefree Polices and Permitting the Use of Different Types of E-Cigarettes.

Comprehensive smokefree policies in health care settings can have a positive impact on patients' smoking behaviour, but implementation is impeded by concern that surreptitious smoking may increase fire incidents. We investigated the incidence of routinely reported fire and false alarm incidents in a large mental health organisation in England over an 81-month period when different elements of a smokefree policy were implemented. We used negative binomial regression models to test associations between rates of fire and false alarm incidents and three hospital smokefree policy periods with mutual adjustment for occupied bed days: (1) an indoor policy which allowed disposable e-cigarettes; (2) a comprehensive policy which allowed disposable e-cigarettes; and (3) a comprehensive policy with all e-cigarette types allowed. We identified 90 fires and 200 false alarms. Fires decreased (incidence rate ratio (IRR): 0.35, 95% CI: 0.17-0.72, p = 0.004) and false alarms increased (IRR: 1.67, 95% CI: 1.02-2.76, p = 0.043), each by approximately two-thirds, when all e-cigarette types were allowed, after adjusting for bed occupancy and the comprehensive smokefree policy. Implementation of smokefree policies in mental health care settings that support use of all types of e-cigarettes may reduce fire risks, though measures to minimise effects of e-cigarette vapour on smoke detector systems may be needed to reduce false alarm incidents.

Systems approaches to population health in Canada: how have they been applied, and what are the insights and future implications for practice?

OBJECTIVES: Systems approaches are promising yet under-utilized methods for tackling complex public health problems. This paper explores how systems approaches are understood in the public health literature, how they have been applied in Canada, the insights, and implications for future practice. METHODS: A rapid review of the literature, including a content analysis and cross-case comparison, was conducted. It was used to distinguish concepts of systems approaches and identify case examples of the application of systems approaches in Canada. Seven cases with a population health perspective (non-health care related) were prioritized for analysis. RESULTS: Systems approaches are a variety of qualitative and quantitative methods that aim to understand a system of interest. Most case examples demonstrated systems thinking methods. Systems science methods were applied predominantly in health care. Only one case of systems science for the social determinants of health was found. Findings indicate that systems approaches were utilized because traditional methods were proving ineffective. These approaches can introduce new ways of thinking, enable collaboration across diverse stakeholders, identify where best to focus action and with what intensity, and provide more robust evidence for decision-making. CONCLUSION: There is a need to build capacity among practitioners for more widespread adoption and use of systems approaches. Population health professionals need to move beyond reductionist approaches, generate more case examples, and use an iterative evaluation approach that prioritizes the application of processes. This will provide further insight into the usefulness of systems approaches as effective methods to address complex health problems.

The evolution of antiviral nucleoside analogues: A review for chemists and non-chemists. Part II: Complex modifications to the nucleoside scaffold.

This is the second of two invited articles reviewing the development of nucleoside analogue antiviral drugs, written for a target audience of virologists and other non-chemists, as well as chemists who may not be familiar with the field. As with the first paper, rather than providing a chronological account, we have chosen to examine particular examples of structural modifications made to nucleoside analogues that have proven fruitful as various antiviral, anticancer, and other therapeutics. The first review covered the more common, and in most cases, single modifications to the sugar and base moieties of the nucleoside scaffold. This paper focuses on more recent developments, especially nucleoside analogues that contain more than one modification to the nucleoside scaffold. We hope that these two articles will provide an informative historical perspective of some of the successfully designed analogues, as well as many candidate compounds that encountered obstacles.

The evolution of nucleoside analogue antivirals: A review for chemists and non-chemists. Part 1: Early structural modifications to the nucleoside scaffold.

This is the first of two invited articles reviewing the development of nucleoside-analogue antiviral drugs, written for a target audience of virologists and other non-chemists, as well as chemists who may not be familiar with the field. Rather than providing a simple chronological account, we have examined and attempted to explain the thought processes, advances in synthetic chemistry and lessons learned from antiviral testing that led to a few molecules being moved forward to eventual approval for human therapies, while others were discarded. The present paper focuses on early, relatively simplistic changes made to the nucleoside scaffold, beginning with modifications of the nucleoside sugars of Ara-C and other arabinose-derived nucleoside analogues in the 1960's. A future paper will review more recent developments, focusing especially on more complex modifications, particularly those involving multiple changes to the nucleoside scaffold. We hope that these articles will help virologists and others outside the field of medicinal chemistry to understand why certain drugs were successfully developed, while the majority of candidate compounds encountered barriers due to low-yielding synthetic routes, toxicity or other problems that led to their abandonment.

Effect of implementation of a smoke-free policy on physical violence in a psychiatric inpatient setting: an interrupted time series analysis.

BACKGROUND: Smoke-free policies are important to protect health and reduce health inequalities. A major barrier to policy implementation in psychiatric hospitals is staff concern that physical violence will increase. We aimed to assess the effect of implementing a comprehensive smoke-free policy on rates of physical assaults in a large UK mental health organisation. METHODS: We did an interrupted time series analysis of incident reports of physical assault 30 months before and 12 months after the implementation of the policy in the inpatient wards of South London and Maudsley National Health Service Foundation Trust, London, UK. We used a quasi-Poisson generalised additive mixed model to model the monthly incidence of physical assaults as a function of several explanatory variables. FINDINGS: 4550 physical assaults took place between April 1, 2012, and Sept 30, 2015; 225 (4·9%) of which were smoking-related. After adjustment for temporal and seasonal trends and key confounders (sex, age, schizophrenia or related disorders, or having been sectioned under the Mental Health Act), there was a 39% reduction in the number of physical assaults per month after the policy introduction compared with beforehand (incidence rate ratio 0·61, 95% CI 0·53-0·70; p<0·0001). INTERPRETATION: Introduction of a comprehensive smoke-free policy appeared to reduce the incidence of physical assaults. Adequately resourced smoke-free policies could be part of broader violence reduction strategies in psychiatric settings. FUNDING: National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care South London (King's College Hospital NHS Foundation Trust).

Predictors of adherence to a new erythropoiesis-stimulating agent inpatient ordering policy: A cross-sectional study.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) are recommended for treating anemia in patients with chronic kidney disease and end-stage renal disease. However, misappropriate and over-use of these agents can be costly and unnecessary in some settings. OBJECTIVE: The primary aim was to identify predictors of adherence to a newly approved ESA inpatient ordering policy. The secondary aims were to evaluate the impact of a 5-day delay in the initiation of ESA therapy on ESA usage, hemoglobin (Hb) levels, and costs. METHODS: This retrospective observational record review included a sample of adult patients admitted to four tertiary care hospitals from November 1, 2013 to August 31, 2014. Multivariable logistic and linear regression analyses were used to calculate the odds of adherence to the new ESA inpatient ordering policy and the impact of this policy on discharge Hb level, respectively. RESULTS: A total of 242 patients were included. The majority of the prescribers (77%) adhered to the new ESA ordering policy. Hemoglobin (OR = 1.306; 95% CI: 1.03-1.65) and ferritin (OR = 3.91; 95% CI: 1.23-12.51) levels at admission and length of hospital stay were positively correlated with the odds of patients receiving ESAs after day 5 (OR = 1.12; 95% CI:1.05-1.20). Furthermore, adherence to the new policy did not have a significant impact on discharge Hb level (ß = 0.02349; P = 0.895). CONCLUSIONS: Prescribers were adherent to a 5-day delay in the initiation of ESA therapy policy which resulted in a reduction in ESA usage, did not impact the discharge Hb levels, and was proven to be cost effective.

Evaluation of doripenem utilization and susceptibilities at a large urban hospital.

BACKGROUND: Bacterial resistance presents a constant challenge in the treatment of hospitalized patients, particularly with Gram-negative infections. Carbapenems have an important role in the treatment of resistant nosocomial organisms. Doripenem, a recently approved carbapenem, has shown efficacy in clinical trials, but there is little published data on utilization in a general patient population. OBJECTIVE: The clinical utilization of doripenem in a general adult inpatient population was evaluated during a carbapenem formulary conversion. SETTING: A 706-bed acute care tertiary hospital serving an urban community. METHODS: After formulary conversion to doripenem, the first 100 patients to receive doripenem were included in the analysis. Baseline characteristics were recorded for each patient, along with indication for treatment, prescribing physician, dose and frequency of doripenem and duration of treatment. Patients were monitored for adverse reactions to doripenem. Bacterial culture results were recorded. For positive cultures, doripenem susceptibility was determined by Etest. Patients were followed until discontinuation of antibiotic therapy, discharge or death to determine treatment outcomes. Successful treatment was defined as clinical or microbiological cure, while patients with infection-related mortality or requiring subsequent antibiotics for the index infection were considered treatment failure. MAIN OUTCOME MEASURES: Clinical utilization of doripenem, including indications and doses used. RESULTS: Doripenem treatment was recorded in 102 patients. The most common indications for treatment were pneumonia and sepsis. The majority of doripenem orders were written by Infectious Disease or Pulmonology Services. Forty-nine patients were treated successfully with doripenem and six patients experienced treatment failure. The remainder of patients were not evaluable by predefined outcomes criteria. Adverse events were reported in eight patients and included acute renal failure, Clostridium difficile-associated diarrhea and seizures. Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa were the most common organisms in culture results. Doripenem demonstrated in vitro activity against 81% of all organisms and susceptibility results had >90% correlation with meropenem and imipenem susceptibilities. CONCLUSION: In our limited sample size, doripenem was safe and effective against various types of infections in a general inpatient population with similar bacterial susceptibilities to other cabapenems. Doripenem was utilized for appropriate indications, but doses were frequently outside the manufacturers labeling. Adverse events were uncommon, and no serious adverse events were directly associated with doripenem treatment.

Case study of the use of evaluation evidence to inform diabetes prevention programming in two Canadian health regions: effectiveness of evaluation evidence.

This study compares the use of evidence in two 18-month Canadian projects with a similar goal: improved prevention of type II diabetes in women from ethno-cultural communities with a gestational diabetes diagnosis. Evidence used for both projects included epidemiological data and research literature, needs assessments with the target population, and project evaluations. Contexts for the use of evidence differed between the two projects in terms of the innovation and its level of complexity; organizational context and system readiness for change; and partnership characteristics. This study showed that while evidence played some role in determining project success, it was but one factor in deciding how project activities were (or were not) sustained.

Activities of Memphis-area hospitals to meet National Patient Safety Goals for warfarin therapy.

PURPOSE: The activities of Memphis hospitals to meet National Patient Safety Goals (NPSGs) for warfarin therapy are described. SUMMARY: In March 2008, leadership from the Mid-South College of Clinical Pharmacy (MSCCP), a local chapter of the American College of Clinical Pharmacy, commissioned a task force on anticoagulation, comprising pharmacy administrators, clinical pharmacy practitioners, and pharmacy faculty from local hospitals within the greater Memphis area. The charge of the task force was to (1) identify practice variations in regard to NPSG.03.05.01, (2) develop professional collaboration among both academic and nonacademic institutions to share policy and protocol development, and (3) facilitate all institutions in meeting the deadlines set forth by the Joint Commission. The MSCCP Task Force on Anticoagulation project was successful in promoting collaboration among multiple institutions and clinical practitioners in the Memphis area. There was no one-size-fits-all approach; however, meetings and discussions were beneficial and led to idea generation. Having input from multiple institutions in different clinical settings with varying levels of experience created a rich environment from which all institutions benefited. For example, smaller institutions felt that they drew support for physician acceptance with protocol approval based on the knowledge of the policies approved or lessons learned at larger institutions. In addition, the larger institutions felt that the working group was helpful in validating their interpretation of the NPSG elements. CONCLUSION: The MSCCP Task Force on Anticoagulation project was successful in promoting collaboration among multiple institutions and clinical practitioners to offer solutions to meet NPSG.03.05.01 as it related to the needs of each institution.