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Withdrawal reactions when coming off antidepressants have long been neglected or minimised. It took almost two decades after the selective serotonin reuptake inhibitors (SSRIs) entered the market for the first systematic review to be published. More reviews have followed, demonstrating that the dominant and long-held view that withdrawal is mostly mild, affects only a small minority and resolves spontaneously within 1–2 weeks, was at odd with the sparse but growing evidence base. What the scientific literature reveals is in close agreement with the thousands of service user testimonies available online in large forums. It suggests that withdrawal reactions are quite common, that they may last from a few weeks to several months or even longer, and that they are often severe. These findings are now increasingly acknowledged by official professional bodies and societies.
Clinical Enterobacteriacae isolates with a colistin minimum inhibitory concentration (MIC) ≥4 mg/L from a United States hospital were screened for the mcr-1 gene using real-time polymerase chain reaction (RT-PCR) and confirmed by whole-genome sequencing. Four colistin-resistant Escherichia coli isolates contained mcr-1. Two isolates belonged to the same sequence type (ST-632). All subjects had prior international travel and antimicrobial exposure.
It is important to distinguish between a theory and the hypotheses that are derived from it, on the one hand, and a theoretical framework on the other. The crucial criterion for judging a theory, in addition to its explanatory value, is its ability to make useful predictions. A framework functions at a higher level of abstraction. The level can vary between a narrow, “local” framework restricted to a well-specified research domain and one that has a wider coverage, ending up with frameworks that also facilitate interdisciplinary research projects. What all frameworks have in common is that they contain some commitments that cannot be significantly altered: this is the framework’s metatheory. Then there are the areas where variation is perfectly possible, allowing researchers to carry out many alternative applications of the metatheory that defines that particular framework.
Antipseudomonal carbapenems are an important target for antimicrobial stewardship programs. We evaluated the impact of formulary restriction and preauthorization on relative carbapenem use for medical and surgical intensive care units at a large, urban academic medical center using interrupted time-series analysis.
Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
Reliable predictors of extubation readiness are needed and may reduce morbidity related to extubation failure. We aimed to examine the relationship between changes in pre-extubation near-infrared spectroscopy measurements from baseline and extubation outcomes after neonatal cardiac surgery.
Materials and Methods:
In this retrospective cross-sectional multi-centre study, a secondary analysis of prospectively collected data from neonates who underwent cardiac surgery at seven tertiary-care children’s hospitals in 2015 was performed. Extubation failure was defined as need for re-intubation within 72 hours of the first planned extubation attempt. Near-infrared spectroscopy measurements obtained before surgery and before extubation in patients who failed extubation were compared to those of patients who extubated successfully using t-tests.
Near-infrared spectroscopy measurements were available for 159 neonates, including 52 with single ventricle physiology. Median age at surgery was 6 days (range: 1–29 days). A total of 15 patients (9.4 %) failed extubation. Baseline cerebral and renal near-infrared spectroscopy measurements were not statistically different between those who were successfully extubated and those who failed, but pre-extubation cerebral and renal values were significantly higher in neonates who extubated successfully. An increase from baseline to time of extubation values in cerebral oximetry saturation by ≥ 5 % had a positive predictive value for extubation success of 98.6 % (95%CI: 91.1–99.8 %).
Pre-extubation cerebral near-infrared spectroscopy measurements, when compared to baseline, were significantly associated with extubation outcomes. These findings demonstrate the potential of this tool as a valuable adjunct in assessing extubation readiness after paediatric cardiac surgery and warrant further evaluation in a larger prospective study.
Issues of sexual reproduction lie at the core of evolutionary thinking, which often places an emphasis on how individuals attempt to maximise the number of successful offspring that they can produce. At first sight, it may therefore appear that individuals who opt for gender-affirming medical interventions are acting in ways that are evolutionarily disadvantageous. However, there are persuasive hypotheses that might make sense of such choices in evolutionary terms and we explore these here. It is premature to claim knowledge of the extent to which evolutionary arguments can usefully be applied to issues of gender identity, although worth reflecting on the extent to which nature tends towards diversity in matters of sex and gender. The importance of acknowledging and respecting different views in this domain, as well as recognising both the uncertainty and likely multiplicity of causal pathways, has implications for clinicians. We make some suggestions about how clinicians might best respond when faced with requests from patients in this area.
After reading this article you will be able to:
•understand evolutionary arguments about diversity in human gender identity
•identify strengths and weaknesses in evolutionary arguments applied to transgender issues
•appreciate the range and diversity of gender experience and gender expression among people who present to specialist gender services, as well as the likely complexities of their reasons for requesting medical intervention.
DECLARATION OF INTEREST
The authors are members of the evo-psychotherapy study group at the Tavistock Clinic, London. The aim of the group is to promote evolutionary thinking in psychotherapy and psychiatry.
Hand hygiene compliance rates were estimated using direct observations. An AHHMS, installed on 4 nursing units in a sequential manner, determined hand hygiene performance rates, expressed as the number of hand hygiene events performed upon entering and exiting patient rooms divided by the number of room entries and exits. Additional strategies implemented to improve hand hygiene included goal setting, hospital leadership support, feeding AHHMS data back to healthcare personnel, and use of Toyota Kata performance improvement methods. HAIs were defined using National Healthcare Safety Network criteria.
Hand hygiene compliance rates generated by direct observation were substantially higher than performance rates generated by the AHHMS. Installation of the AHHMS without supplementary activities did not yield sustained improvement in hand hygiene performance rates. Implementing several supplementary strategies resulted in a statistically significant 85% increase in hand hygiene performance rates (P < .0001). The incidence density of non–Clostridioies difficile HAIs decreased by 56% (P = .0841), while C. difficile infections increased by 60% (P = .0533) driven by 2 of the 4 study units.
Implementation of an AHHMS, when combined with several supplementary strategies as part of a multimodal program, resulted in significantly improved hand hygiene performance rates. Reductions in non–C. difficile HAIs occurred but were not statistically significant.
Antimicrobial stewardship programs (ASPs) are effective in developed countries. In this study, we assessed the effectiveness of an infectious disease (ID) physician–driven post-prescription review and feedback as an ASP strategy in India, a low middle-income country (LMIC).
Design and setting:
This prospective cohort study was carried out for 18 months in 2 intensive care units of a tertiary-care hospital, consisting of 3 phases: baseline, intervention, and follow up. Each phase spanned 6 months.
Patients aged ≥15 years receiving 48 hours of study antibiotics were recruited for the study.
During the intervention phase, an ID physician reviewed the included cases and gave alternate recommendations if the antibiotic use was inappropriate. Acceptance of the recommendations was measured after 48 hours. The primary outcome of the study was days of therapy (DOT) per 1,000 study patient days (PD).
Overall, 401 patients were recruited in the baseline phase, 381 patients were recruited in the intervention phase, and 379 patients were recruited in the follow-up phase. Antimicrobial use decreased from 831.5 during the baseline phase to 717 DOT per 1,000 PD in the intervention phase (P < .0001). The effect was sustained in the follow-up phase (713.6 DOT per 1,000 PD). De-escalation according to culture susceptibility improved significantly in the intervention phase versus the baseline phase (42.7% vs 23.6%; P < .0001). Overall, 73.3% of antibiotic prescriptions were inappropriate. Recommendations by the ID team were accepted in 60.7% of the cases.
The ID physician–driven implementation of an ASP was successful in reducing antibiotic utilization in an acute-care setting in India.
A 2018 workshop on the White Mountain Apache Tribe lands in Arizona examined ways to enhance investigations into cultural property crime (CPC) through applications of rapidly evolving methods from archaeological science. CPC (also looting, graverobbing) refers to unauthorized damage, removal, or trafficking in materials possessing blends of communal, aesthetic, and scientific values. The Fort Apache workshop integrated four generally partitioned domains of CPC expertise: (1) theories of perpetrators’ motivations and methods; (2) recommended practice in sustaining public and community opposition to CPC; (3) tactics and strategies for documenting, investigating, and prosecuting CPC; and (4) forensic sedimentology—uses of biophysical sciences to link sediments from implicated persons and objects to crime scenes. Forensic sedimentology served as the touchstone for dialogues among experts in criminology, archaeological sciences, law enforcement, and heritage stewardship. Field visits to CPC crime scenes and workshop deliberations identified pathways toward integrating CPC theory and practice with forensic sedimentology’s potent battery of analytic methods.
To determine whether oral vancomycin prophylaxis accompanying systemic antibiotics reduces the risk of relapse in patients with history of Clostridioides difficile infection (CDI).
Retrospective cohort study.
Adult inpatients with a history of CDI who received systemic antibiotics in either of 2 hospitals between January 2009 and June 2015.
We compared relapse rates in patients who started oral vancomycin concurrently with systemic antibiotics (exposed group) versus those who did not. We assessed for CDI relapse by toxin or nucleic acid testing at 90 days. We used inverse probability weighting and machine learning to adjust for confounders, to estimate propensity for treatment, and to calculate odds ratios for CDI relapse. We performed secondary analyses limited to toxin-positive relapses, patients with 1 versus >1 prior CDI episodes, and patients who received oral vancomycin on each antibiotic day.
CDI relapse occurred within 90 days in 19 of 193 exposed patients (9.8%) versus 53 of 567 unexposed patients (9.4%; unadjusted odds ratio [OR], 1.06; 95% confidence interval [CI], 0.60–1.81; adjusted OR, 0.63; 95% CI, 0.35–1.14). CDI relapses at 90 days were less frequent in exposed patients with only 1 prior episode of CDI (OR, 0.42; 95% CI, 0.19–0.93) but not in those with >1 prior episode (OR, 1.19; 95% CI, 0.42–3.33). Our findings were consistent with a lack of benefit of oral vancomycin when restricting results to toxin-positive relapses and to patients who received vancomycin each antibiotic day.
Prophylactic oral vancomycin was not consistently associated with reduced risk of CDI relapse among hospitalized patients receiving systemic antibiotics. However, patients with only 1 prior CDI episode may benefit.
The Erasmus Plus programme ‘Innovative Education and Training in high power laser plasmas’, otherwise known as PowerLaPs, is described. The PowerLaPs programme employs an innovative paradigm in that it is a multi-centre programme where teaching takes place in five separate institutes with a range of different aims and styles of delivery. The ‘in class’ time is limited to four weeks a year, and the programme spans two years. PowerLaPs aims to train students from across Europe in theoretical, applied and laboratory skills relevant to the pursuit of research in laser–plasma interaction physics and inertial confinement fusion (ICF). Lectures are intermingled with laboratory sessions and continuous assessment activities. The programme, which is led by workers from the Technological Educational Institute (TEI) of Crete, and supported by co-workers from the Queen’s University Belfast, the University of Bordeaux, the Czech Technical University in Prague, Ecole Polytechnique, the University of Ioannina, the University of Salamanca and the University of York, has just completed its first year. Thus far three Learning Teaching Training (LTT) activities have been held, at the Queen’s University Belfast, the University of Bordeaux and the Centre for Plasma Physics and Lasers (CPPL) of TEI Crete. The last of these was a two-week long Intensive Programme (IP), while the activities at the other two universities were each five days in length. Thus far work has concentrated upon training in both theoretical and experimental work in plasma physics, high power laser–matter interactions and high energy density physics. The nature of the programme will be described in detail and some metrics relating to the activities carried out to date will be presented.
Uncontrolled pain in advanced cancer is a common problem and has significant impact on individuals’ quality of life and use of healthcare resources. Interventions to help manage pain at the end of life are available, but there is limited economic evidence to support their wider implementation. We conducted a case study economic evaluation of two pain self-management interventions (PainCheck and Tackling Cancer Pain Toolkit [TCPT]) compared with usual care.
We generated a decision-analytic model to facilitate the evaluation. This modelled the survival of individuals at the end of life as they moved through pain severity categories. Intervention effectiveness was based on published meta-analyses results. The evaluation was conducted from the perspective of the U.K. health service provider and reported cost per quality-adjusted life-year (QALY).
PainCheck and TCPT were cheaper (respective incremental costs -GBP148 [-EUR168.53] and -GBP474 [-EUR539.74]) and more effective (respective incremental QALYs of 0.010 and 0.013) than usual care. There was a 65 percent and 99.5 percent chance of cost-effectiveness for PainCheck and TCPT, respectively. Results were relatively robust to sensitivity analyses. The most important driver of cost-effectiveness was level of pain reduction (intervention effectiveness). Although cost savings were modest per patient, these were considerable when accounting for the number of potential intervention beneficiaries.
Educational and monitoring/feedback interventions have the potential to be cost-effective. Economic evaluations based on estimates of effectiveness from published meta-analyses and using a decision modeling approach can support commissioning decisions and implementation of pain management strategies.