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Anxiety disorders and treatment-resistant major depressive disorder (TRD) are often comorbid. Studies suggest ketamine has anxiolytic and antidepressant properties.
Aims
To investigate if subcutaneous racemic ketamine, delivered twice weekly for 4 weeks, reduces anxiety in people with TRD.
Method
The Ketamine for Adult Depression Study was a multisite 4-week randomised, double-blind, active (midazolam)-controlled trial. The study initially used fixed low dose ketamine (0.5 mg/kg, cohort 1), before protocol revision to flexible, response-guided dosing (0.5–0.9 mg/kg, cohort 2). This secondary analysis assessed anxiety using the Hamilton Anxiety (HAM-A) scale (primary measure) and ‘inner tension’ item 3 of the Montgomery–Åsberg Depression Rating Scale (MADRS), at baseline, 4 weeks (end treatment) and 4 weeks after treatment end. Analyses of change in anxiety between ketamine and midazolam groups included all participants who received at least one treatment (n = 174), with a mixed effects repeated measures model used to assess the primary anxiety measure. The trial was registered at www.anzctr.org.au (ACTRN12616001096448).
Results
In cohort 1 (n = 68) the reduction in HAM-A score was not statistically significant: −1.4 (95% CI [−8.6, 3.2], P = 0.37), whereas a significant reduction was seen for cohort 2 (n = 106) of −4.0 (95% CI [−10.6, −1.9], P = 0.0058), favouring ketamine over midazolam. These effects were mediated by total MADRS and were not maintained at 4 weeks after treatment end. MADRS item 3 was also significantly reduced in cohort 2 (P = 0.026) but not cohort 1 (P = 0.96).
Conclusion
Ketamine reduces anxiety in people with TRD when administered subcutaneously in adequate doses.
The U.S. Centers for Disease Control and Prevention encourages nurses to evaluate penicillin allergies as part of hospital-based antibiotic stewardship programs. We evaluated the feasibility of an implementation strategy to improve nurses’ comprehensive documentation of penicillin allergies. We defined feasibility as the uptake and acceptability of documentation procedures.
Outpatient surgical areas of an academic medical center located in the U.S.
Intervention:
The implementation strategy was guided by the Capability, Opportunity, Motivation Model for Behavior Change and included, building an interdisciplinary coalition to iteratively evaluate the implementation effort, educational meetings with surgical prescribers and perioperative nurses, the development and distribution of educational pocket cards, and structured communication messages in the electronic medical record.
Results:
A total of 426 patients with 487 penicillin allergy records (216 records pre-implementation period, 271 records post-implementation period) were analyzed. Penicillin allergy documentation contained the following information in the pre- versus post-implementation period: symptoms of the reaction (87% vs 87%), timing/years since reaction (8% vs 26%), onset of reaction in relation to taking penicillin (0% vs 21%), how symptoms resolved (0% vs 21%), and penicillin re-exposure (3% vs 21%). Focus groups revealed nurses perceived documentation procedures as highly acceptable. Major drivers of acceptability included the perceived effectiveness of a detailed allergy history and self-efficacy in conducting a detailed allergy history.
Conclusions:
Nurses perceived the comprehensive documentation of penicillin allergy history intervention as acceptable, and uptake improved following a theory-informed implementation strategy. We offer implementation strategy components to facilitate nurses’ engagement in penicillin allergy evaluation.
Visceral leishmaniasis (VL) is a severe infectious disease caused by protozoan parasites of the Leishmania donovani complex. Blood cytokine concentrations in VL patients can inform us about underlying immunopathogenesis and may serve as a biomarker for treatment effectiveness. However, cytokine levels have not yet been studied in VL patients from Kenya, where case load is high. This study measured the serum cytokine profile, blood parasite load and clinical and haematological features of VL patients from West Pokot County, Kenya, over the course of treatment with sodium stibogluconate and paromomycin (SSG-PM). VL patients recruited at the hospital presented with splenomegaly and weight loss, and frequently had pancytopenia and anaemia. Median Leishmania parasite load in blood, determined with real-time polymerase chain reaction, was 2.6 × 104 parasite equivalents mL−1. Compared to endemic healthy controls, serum interferon gamma (IFN-γ), interleukin 5 (IL-5), IL-6, IL-10, IL-12p70, IL-17A and IL-27 were significantly elevated in untreated VL patients. Severe VL was associated with higher IL-10 and lower IFN-γ levels. After 17 daily injections with SSG-PM, disease symptoms disappeared, leukocyte and thrombocyte counts significantly increased, and blood parasite load decreased to undetectable levels in all VL patients. There was a significant decrease in IL-10 and IL-6, whereas IL-17A levels increased; the remaining cytokines showed no significant concentration change during treatment. In conclusion, the results suggest that SSG-PM treatment of VL patients from West Pokot was effective. Moreover, both inflammatory and regulatory immune responses appeared to decrease during treatment, although the increase in IL-17A could reflect a partial continuation of immune activation.
Background: The CDC recommends that nurses improve the evaluation of penicillin allergies as part of antimicrobial stewardship programs. We evaluated the feasibility of a multifaceted implementation strategy to improve nurses’ documentation of penicillin allergy histories and to encourage nurses to notify prescribers of patients with low-risk symptoms of reported penicillin allergy. The implementation strategy was guided by the COM-B model of behavior change and addressed nurses’ capability, opportunity, and motivation to implement practices (Figure 1). The implementation strategy included education on the STORY mnemonic that details the questions of a penicillin allergy history, education on low-risk symptoms of penicillin allergy, dot phrases in EPIC to facilitate nurses’ documentation of STORY and communication of patients with low-risk penicillin allergy symptoms, and educational pocket cards and flyers. We define feasibility as the implementation and acceptability of practices. Methods: This was a six-month feasibility study conducted in an outpatient perioperative area. We compared penicillin allergy documentation pre- and post- implementation strategy and report on nurses’ notification of prescribers regarding patients with low-risk penicillin allergies in the post-implementation period. We engaged nurses in a focus group to assess factors that facilitated or hindered practice adoption. Results: A total of 426 unique patients with 482 penicillin allergy records were included in our study (n= 207 records pre-implementation, n = 275 records post-implementation). We found little to no change in the percentage of records that included symptom information post vs. pre-implementation (88.36% vs 88.41%). A greater percentage of allergy records in the post vs. pre-implementation periods included information on: timing/years since reaction (25.6% vs. 8.2%), onset of reaction (20.7% vs. 0%), resolution of symptoms (20.4% vs. 0%), and penicillin re-exposure (21.1% vs. 2.4%). There were 24 documented instances of nurses’ notifying prescribers of patients with a low-risk penicillin allergy. Focus group data revealed nurses perceived their comprehensive documentation of penicillin allergies highly acceptable and likely to improve patient care and outcomes. Whereas nurses’ notification of prescribers concerning patients meeting low-risk penicillin allergy criteria had little appeal. Nurses described the STORY mnemonic, pocket cards describing the penicillin allergy assessment mnemonic, and the associated dot phrase in EPIC as particularly helpful. Conclusions: A multifaceted implementation strategy showed promise in improving the comprehensive documentation of penicillin allergy histories. Future studies are needed to determine the efficacy of the multifaceted implementation strategy on penicillin allergy documentation, the selection of antibiotic prophylactic treatment, and clinical outcomes among surgical patients.
We report the discovery of an ancient forest bed near Stanley, on the Falkland Islands, the second such ancient deposit identified on the South Atlantic island archipelago that is today marked by the absence of native tree species. Fossil pollen, spores and wood fragments preserved in this buried deposit at Tussac House show that the source vegetation was characterized by a floristically diverse rainforest dominated by Nothofagus-Podocarpaceae communities, similar to cool temperate Nothofagus forests/woodlands and Magellanic evergreen Nothofagus rainforests. The age limit of the deposit is inferred from the stratigraphic distribution of fossil pollen species transported by wind, birds or ocean currents from southern Patagonia, as well as similar vegetation types observed across the broader region. The deposit is suggested to be between Late Oligocene and Early Miocene, making it slightly older than the previously analysed Neogene West Point Island forest bed (200 km west of Tussac House). The combined evidence adds to our current knowledge of the role of climate change and transoceanic dispersal of plant propagules in shaping high-latitude ecosystems in the Southern Hemisphere during the late Palaeogene and Neogene.
Characterize antibiotic prescribing behaviors at an Indian palliative care center after the initiation of the Antibiotic Order Form (AOF): an antibiotic stewardship program involving a paper form to track antibiotic use and to provide prescription guidelines.
Design:
Retrospective chart review.
Setting:
Trivandrum Institute of Palliative Sciences (TIPS) is a palliative care organization in Kerala, India.
Methods:
Antibiotic prescription data and patient data were collected for adult patients treated at TIPS between January 1, 2017, and October 31, 2019. Descriptive statistics and a Zero-Inflated Poisson regression model were used to analyze antibiotic prescriptions. AOF completion and prescription concordance with institutional guidelines were also evaluated.
Results:
Out of 7,450 unique patients, 675 (9%) were prescribed 1,448 antibiotics. Age was the strongest factor in determining the number of antibiotic courses with each additional year of age decreasing the expected antibiotic prescription count by 2% per year. The most common antibiotics prescribed were topical metronidazole (44%) and penicillins (29%). Among patients who died, 5% were prescribed antibiotics within the final month of life. In total, 32% of antibiotic prescriptions were documented in AOFs, and 18% were concordant with all institutional antibiotic prescribing guidelines.
Conclusions:
This study is the first to analyze an antibiotic stewardship intervention in a palliative care setting within a low- and middle-income country. This retrospective study provides a benchmark of antibiotic use within Indian palliative care and highlights areas for future stewardship research including topical metronidazole use within palliative care and higher rates of antibiotic use among younger palliative care patients.
Trauma is prevalent amongst early psychosis patients and associated with adverse outcomes. Past trials of trauma-focused therapy have focused on chronic patients with psychosis/schizophrenia and comorbid Post-Traumatic Stress Disorder (PTSD). We aimed to determine the feasibility of a large-scale randomized controlled trial (RCT) of an Eye Movement Desensitization and Reprocessing for psychosis (EMDRp) intervention for early psychosis service users.
Methods
A single-blind RCT comparing 16 sessions of EMDRp + TAU v. TAU only was conducted. Participants completed baseline, 6-month and 12-month post-randomization assessments. EMDRp and trial assessments were delivered both in-person and remotely due to COVID-19 restrictions. Feasibility outcomes were recruitment and retention, therapy attendance/engagement, adherence to EMDRp treatment protocol, and the ‘promise of efficacy’ of EMDRp on relevant clinical outcomes.
Results
Sixty participants (100% of the recruitment target) received TAU or EMDR + TAU. 83% completed at least one follow-up assessment, with 74% at 6-month and 70% at 12-month. 74% of EMDRp + TAU participants received at least eight therapy sessions and 97% rated therapy sessions demonstrated good treatment fidelity. At 6-month, there were signals of promise of efficacy of EMDRp + TAU v. TAU for total psychotic symptoms (PANSS), subjective recovery from psychosis, PTSD symptoms, depression, anxiety, and general health status. Signals of efficacy at 12-month were less pronounced but remained robust for PTSD symptoms and general health status.
Conclusions
The trial feasibility criteria were fully met, and EMDRp was associated with promising signals of efficacy on a range of valuable clinical outcomes. A larger-scale, multi-center trial of EMDRp is feasible and warranted.
This chapter examines the history of critical interpretations of the Australian novel from the mid- to late nineteenth century through the late twentieth century. In the colonial period, poetry and drama were often held in greater esteem than the novel as literary forms, but by the late nineteenth century the novel had become a gauge of the incipient nation’s evolution towards maturity or ‘civilisation’. Debates about contemporary realism and naturalism cut across these concerns. Attempts were made across the first half of the twentieth century to define the distinctive features of the Australian novel and its role in a national literary tradition, but often in terms of their absence rather than their presence. Much of the critical discussion of the Australian novel occurred outside the universities, in a public culture of books and reading. The field was redefined from the late 1950s to the 1970s through academic criticism, and then through the radical revisions of feminist, postcolonial and other poststructuralist approaches. The novel remained firmly at the centre of such debates.
This section introduces the structure and logic of The Cambridge History of the Australian Novel. It considers the role of the Australian novel in local, national and international contexts; its engagement as a cultural technology in the major historical events of Australia’s history; its transnational positioning; and changes over time in terms of writing, publishing, readership and genre structures. The history of publishing and of criticism of the Australian novel are described. The book’s structure from the colonial period until the present is outlined while readers are invited to read across essays for ongoing and changing thematic concerns.
Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed.
Aims
To assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD. Trial registration: ACTRN12616001096448 at www.anzctr.org.au.
Method
This phase 3, double-blind, randomised, active-controlled multicentre trial was conducted at seven mood disorders centres in Australia and New Zealand. Participants received twice-weekly subcutaneous racemic ketamine or midazolam for 4 weeks. Initially, the trial tested fixed-dose ketamine 0.5 mg/kg versus midazolam 0.025 mg/kg (cohort 1). Dosing was revised, after a Data Safety Monitoring Board recommendation, to flexible-dose ketamine 0.5–0.9 mg/kg or midazolam 0.025–0.045 mg/kg, with response-guided dosing increments (cohort 2). The primary outcome was remission (Montgomery-Åsberg Rating Scale for Depression score ≤10) at the end of week 4.
Results
The final analysis (those who received at least one treatment) comprised 68 in cohort 1 (fixed-dose), 106 in cohort 2 (flexible-dose). Ketamine was more efficacious than midazolam in cohort 2 (remission rate 19.6% v. 2.0%; OR = 12.1, 95% CI 2.1–69.2, P = 0.005), but not different in cohort 1 (remission rate 6.3% v. 8.8%; OR = 1.3, 95% CI 0.2–8.2, P = 0.76). Ketamine was well tolerated. Acute adverse effects (psychotomimetic, blood pressure increases) resolved within 2 h.
Conclusions
Adequately dosed subcutaneous racemic ketamine was efficacious and safe in treating TRD over a 4-week treatment period. The subcutaneous route is practical and feasible.