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To evaluate broad-spectrum intravenous antibiotic use before and after the implementation of a revised febrile neutropenia management algorithm in a population of adults with hematologic malignancies.
Setting and population:
Patients admitted between 2014 and 2018 to the Adult Malignant Hematology service of an acute-care hospital in the United States.
Aggregate data for adult malignant hematology service were obtained for population-level antibiotic use: days of therapy (DOT), C. difficile infections, bacterial bloodstream infections, intensive care unit (ICU) length of stay, and in-hospital mortality. All rates are reported per 1,000 patient days before the implementation of an febrile neutropenia management algorithm (July 2014–May 2016) and after the intervention (June 2016–December 2018). These data were compared using interrupted time series analysis.
In total, 2,014 patients comprised 6,788 encounters and 89,612 patient days during the study period. Broad-spectrum intravenous (IV) antibiotic use decreased by 5.7% with immediate reductions in meropenem and vancomycin use by 22 (P = .02) and 15 (P = .001) DOT per 1,000 patient days, respectively. Bacterial bloodstream infection rates significantly increased following algorithm implementation. No differences were observed in the use of other antibiotics or safety outcomes including C. difficile infection, ICU length of stay, and in-hospital mortality.
Reductions in vancomycin and meropenem were observed following the implementation of a more stringent febrile neutropenia management algorithm, without evidence of adverse outcomes. Successful implementation occurred through a collaborative effort and continues to be a core reinforcement strategy at our institution. Future studies evaluating patient-level data may identify further stewardship opportunities in this population.
Biogenic nanoscale vanadium magnetite is produced by converting V(V)-bearing ferrihydrites through reductive transformation using the metal-reducing bacterium Geobacter sulfurreducens. With increasing vanadium in the ferrihydrite, the amount of V-doped magnetite produced decreased due to V-toxicity which interrupted the reduction pathway ferrihydrite–magnetite, resulting in siderite or goethite formation. Fe L2,3 and V L2,3 X-ray absorption spectra and data from X-ray magnetic circular dichroism analysis revealed the magnetite to contain the V in the Fe(III) Oh site, predominately as V(III) but always with a component of V(VI), present a consistent V(IV)/V(III) ratio in the range 0.28 to 0.33. The bacteriogenic production of V-doped magnetite nanoparticles from V-doped ferrihydrite is confirmed and the work reveals that microbial reduction of contaminant V(V) to V(III)/V(IV) in the environment will occur below the Fe-redox boundary where it will be immobilised in biomagnetite nanoparticles.
To examine the factors that are associated with changes in depression in people with type 2 diabetes living in 12 different countries.
People with type 2 diabetes treated in out-patient settings aged 18–65 years underwent a psychiatric assessment to diagnose major depressive disorder (MDD) at baseline and follow-up. At both time points, participants completed the Patient Health Questionnaire (PHQ-9), the WHO five-item Well-being scale (WHO-5) and the Problem Areas in Diabetes (PAID) scale which measures diabetes-related distress. A composite stress score (CSS) (the occurrence of stressful life events and their reported degree of ‘upset’) between baseline and follow-up was calculated. Demographic data and medical record information were collected. Separate regression analyses were conducted with MDD and PHQ-9 scores as the dependent variables.
In total, there were 7.4% (120) incident cases of MDD with 81.5% (1317) continuing to remain free of a diagnosis of MDD. Univariate analyses demonstrated that those with MDD were more likely to be female, less likely to be physically active, more likely to have diabetes complications at baseline and have higher CSS. Mean scores for the WHO-5, PAID and PHQ-9 were poorer in those with incident MDD compared with those who had never had a diagnosis of MDD. Regression analyses demonstrated that higher PHQ-9, lower WHO-5 scores and greater CSS were significant predictors of incident MDD. Significant predictors of PHQ-9 were baseline PHQ-9 score, WHO-5, PAID and CSS.
This study demonstrates the importance of psychosocial factors in addition to physiological variables in the development of depressive symptoms and incident MDD in people with type 2 diabetes. Stressful life events, depressive symptoms and diabetes-related distress all play a significant role which has implications for practice. A more holistic approach to care, which recognises the interplay of these psychosocial factors, may help to mitigate their impact on diabetes self-management as well as MDD, thus early screening and treatment for symptoms is recommended.
Silvery-Thread Moss (Bryum argenteum Hedw.) is an undesirable invader of golf course putting greens across North America, establishing colonies and proliferating despite practices to suppress it. The goal was to grow genotypes of green (growing in putting greens) and native (growing in habitats outside of putting greens) B. argenteum in a common garden experiment, allowing an experimental test of life-history traits between genotypes from these two habitats. Seventeen collections of green and 17 collections of native B. argenteum were cloned to single genotypes and raised through a minimum of two asexual generations in the lab. A culture of each genotype was initiated using a single detached shoot apex and was allowed to grow for 6 mo under conditions of inorganic nutrients present and absent. Compared with genotypes from native habitats, genotypes of B. argenteum from putting greens exhibited earlier shoot regeneration and shoot induction, faster protonemal extension, longer (higher) shoots, lower production of gemmae and bulbils, and greater aerial rhizoid cover, and showed similar tendencies of chlorophyll fluorescence properties and chlorophyll content. Cultures receiving no inorganic nutrients produced less chlorophyll content, greatly reduced growth, and bleaching of shoots. Mosses from putting greens establish more quickly, grow faster, produce more abundant rhizoids, and yet do not produce as many specialized asexual propagules compared with mosses of the same species from native habitats. The highly managed putting green environment has either selected for a suite of traits that allow the moss to effectively compete with grasses, or genotypic diversity is very high in this species, allowing a set of specialized genotypes to colonize the putting green from native habitats. Successful golf course weeds have been able to adapt to this highly competitive environment by selection acting on traits or genotypes to produce plants more successful in competing with golf course grasses.
With the increasing enthusiasm to provide cognitive remediation (CR) as an evidence-based practice, questions arise as to what is involved in implementing CR in a large system of care. This article describes the first statewide implementation of CR in the USA, with the goal of documenting the implementation issues that care providers are likely to face when bringing CR services to their patients.
In 2014, the New York State Office of Mental Health set up a Cognitive Health Service that could be implemented throughout the state-operated system of care. This service was intended to broadly address cognitive health, to assure that the cognitive deficits commonly associated with psychiatric illnesses are recognized and addressed, and that cognitive health is embedded in the vocabulary of wellness. It involved creating a mechanism to train staff to recognize how cognitive health could be prioritized in treatment planning as well as implementing CR in state-operated adult outpatient psychiatry clinics.
By 2017, CR was available at clinics serving people with serious mental illness in 13 of 16 adult Psychiatric Centers, located in rural and urban settings throughout New York state. The embedded quality assurance program evaluation tools indicated that CR was acceptable, sustainable, and effective.
Cognitive remediation can be feasibly implemented in large systems of care that provide a multilevel system of supports, a training program that educates broadly about cognitive health and specifically about the delivery of CR, and embedded, ongoing program evaluation that is linked to staff supervision.
Concerns relating to increased use of psychotropic medication contrast with those of under-treatment and under-recognition of common mental disorders in children and young people (CYP) across developed countries. Little is known about the indications recorded for antidepressant prescribing in primary care in CYP.
This was an electronic cohort study of routinely collected primary-care data from a population of 1.9 million, Wales, UK. Poisson regression was undertaken to model adjusted counts of recorded depression symptoms, diagnoses and antidepressant prescriptions. Associated indications were explored.
3 58 383 registered patients aged 6–18 years between 1 January 2003 and 31 December 2013 provided a total of 19 20 338 person-years of follow-up. The adjusted incidence of antidepressant prescribing increased significantly [incidence rate ratio (IRR) for 2013 = 1.28], mainly in older adolescents. The majority of new antidepressant prescriptions were for citalopram. Recorded depression diagnoses showed a steady decline (IRR = 0.72) while depression symptoms (IRR = 2.41) increased. Just over half of new antidepressant prescriptions were associated with depression (diagnosis or symptoms). Other antidepressant prescribing, largely unlicensed, was associated with diagnoses such as anxiety and pain.
Antidepressant prescribing is increasing in CYP while recorded depression diagnoses decline. Unlicensed citalopram prescribing occurs outside current guidelines, despite its known toxicity in overdose. Unlicensed antidepressant prescribing is associated with a wide range of diagnoses, and while accepted practice, is often not supported by safety and efficacy studies. New strategies to implement current guidance for the management of depression in CYP are required.
Defining minimal important difference (MID) is critical to interpreting patient-reported outcomes data and treatment efficacy in clinical trials. This study estimates the MID for the Weiss Functional Impairment Rating Scale–Parent Report (WFIRS-P) and the Child Health and Illness Profile–Parent Report (CHIP-CE-PRF76) among parents of young people with attention-deficit/hyperactivity disorder (ADHD) in the UK.
Parents of children (6–12 years; n=100) and adolescents (13–17 years; n=117) with ADHD completed a socio-demographic form, the CHIP-CE-PRF76, the WFIRS-P, and the Pediatric Quality of Life scale at baseline and 4 weeks later. At follow-up, a subset of parents completed anchor questions measuring change in the child/adolescent from baseline. MIDs were estimated using anchor-based and distribution-based methods, and separately for children and adolescents.
The MID estimates for overall change in the WFIRS-P total score ranged from 11.31 (standard error of measurement) to 13.47 (anchor) for the total sample. The range of MID estimates for the CHIP-CE-PRF76 varied by domain: 6.80–7.41 (satisfaction), 6.18–7.34 (comfort), 5.60–6.72 (resilience), 6.06–7.57 (risk avoidance), and 4.00–5.63 (achievement) for the total sample. Overall, MID estimates for WFIRS-P MID and CHIP-CE-PRF76 were slightly higher for adolescents than for children.
This study estimated MIDs for these instruments using several methods. The observed convergence of the MID estimates increases confidence in their reliability and could assist clinicians and decision makers in deriving meaningful interpretations of observed changes in the WFIRS-P and CHIP-CE in clinical trials and practice.
We assessed evidence of exposure to viruses and bacteria in an unmanaged and long-isolated population of Soay sheep (Ovis aries) inhabiting Hirta, in the St Kilda archipelago, 65 km west of Benbecula in the Outer Hebrides of Scotland. The sheep harbour many metazoan and protozoan parasites but their exposure to viral and bacterial pathogens is unknown. We tested for herpes viral DNA in leucocytes and found that 21 of 42 tested sheep were infected with ovine herpesvirus 2 (OHV-2). We also tested 750 plasma samples collected between 1997 and 2010 for evidence of exposure to seven other viral and bacterial agents common in domestic Scottish sheep. We found evidence of exposure to Leptospira spp., with overall seroprevalence of 6·5%. However, serological evidence indicated that the population had not been exposed to border disease, parainfluenza, maedi-visna, or orf viruses, nor to Chlamydia abortus. Some sheep tested positive for antibodies against Mycobacterium avium subsp. paratuberculosis (MAP) but, in the absence of retrospective faecal samples, the presence of this infection could not be confirmed. The roles of importation, the pathogen–host interaction, nematode co-infection and local transmission warrant future investigation, to elucidate the transmission ecology and fitness effects of the few viral and bacterial pathogens on Hirta.
Under the alkaline conditions expected in an intermediate-level waste repository, cellulosic material will undergo chemical hydrolysis. This will produce hydrolysis products, some of which can form soluble complexes with some radionuclides. Analyses of samples containing autoclaved tissue and cotton wool incubated in a saturated solution of Ca(OH)2 ( pH > 12) confirmed previous reports that isosaccharinic acid (ISA) is produced from these cellulose polymers at high pH. However, when inoculated with a sediment sample from a hyperalkaline site contaminated with lime-kiln waste, microbial activity was implicated in the enzymatic hydrolysis of cellulose and the subsequent production of acetate. This in turn led to acidification of the microcosms and a marked decrease in ISA production from the abiotic alkali hydrolysis of cellulose. DNA analyses of microbial communities present in the microcosms further support the hypothesis that bacterial activities can have a controlling influence on the formation of organic acids, including ISA, via an interplay between direct and indirect mechanisms. These and previous results imply that microorganisms could have a role in attenuating the mobility of some radionuclides in and around a geological disposal facility, via either the direct biodegradation of ISA or by catalysing cellulose fermentation and therefore preventing the formation of ISA.
North American studies show bipolar disorder is associated with elevated
rates of problem gambling; however, little is known about rates in the
different presentations of bipolar illness.
To determine the prevalence and distribution of problem gambling in
people with bipolar disorder in the UK.
The Problem Gambling Severity Index was used to measure gambling problems
in 635 participants with bipolar disorder.
Moderate to severe gambling problems were four times higher in people
with bipolar disorder than in the general population, and were associated
with type 2 disorder (OR = 1.74, P = 0.036), history of
suicidal ideation or attempt (OR = 3.44, P = 0.02) and
rapid cycling (OR = 2.63, P = 0.008).
Approximately 1 in 10 patients with bipolar disorder may be at moderate
to severe risk of problem gambling, possibly associated with suicidal
behaviour and a rapid cycling course. Elevated rates of gambling problems
in type 2 disorder highlight the probable significance of modest but
unstable mood disturbance in the development and maintenance of such
The emergence of invasive fungal wound infections (IFIs) in combat casualties led to development of a combat trauma-specific IFI case definition and classification. Prospective data were collected from 1133 US military personnel injured in Afghanistan (June 2009–August 2011). The IFI rates ranged from 0·2% to 11·7% among ward and intensive care unit admissions, respectively (6·8% overall). Seventy-seven IFI cases were classified as proven/probable (n = 54) and possible/unclassifiable (n = 23) and compared in a case-case analysis. There was no difference in clinical characteristics between the proven/probable and possible/unclassifiable cases. Possible IFI cases had shorter time to diagnosis (P = 0·02) and initiation of antifungal therapy (P = 0·05) and fewer operative visits (P = 0·002) compared to proven/probable cases, but clinical outcomes were similar between the groups. Although the trauma-related IFI classification scheme did not provide prognostic information, it is an effective tool for clinical and epidemiological surveillance and research.
The common mental disorders (CMDs) of anxiety and depression are the most common form of poor mental health in the general population. Evidence from the small number of previous cohort studies on the role of neighbourhood factors in mental health is inconclusive. We tested the hypothesis that high levels of neighbourhood social cohesion modify an adverse association between change in individual mental health and neighbourhood deprivation.
We carried out a longitudinal multilevel analysis using data from the Caerphilly Health and Social Needs Cohort Study with a 7-year follow-up (n = 4426; age range 18–74 years at baseline). Neighbourhood deprivation and neighbourhood social cohesion were assessed at baseline and change in mental health between follow-up and baseline was assessed using the five-item Mental Health Inventory (MHI-5).
Residence in the most deprived neighbourhoods was negatively associated with change in mental health, after adjusting for baseline individual socio-economic risk factors and transitions in life events. This negative effect was significantly reduced in high social cohesion neighbourhoods. The predicted change in mental health score was calculated for the 10th and 90th centiles of the household low-income distribution. The difference between them was −2.8 in the low social cohesion group and 1.1 in the high cohesion group. The difference between the groups was 3.9 [95% confidence interval (CI) 0.2–7.6].
The public health burden of poor mental health and mental health inequality could potentially be reduced by strengthening social cohesion in deprived neighbourhoods. This offers a mechanism to address the adverse effect of neighbourhood deprivation on population mental health.
Cpefat/fat mice have a point mutation in carboxypeptidase E (Cpe), an exopeptidase that removes C-terminal basic amino acids from intermediates to produce bioactive peptides. The mutation renders the enzyme inactive and unstable. The absence of Cpe activity in these mutants leads to abnormal processing of many peptides, with elevated levels of intermediates and greatly reduced levels of the mature peptides. Cpefat/fat mice develop obesity, diabetes and infertility in adulthood. We examined whether anxiety- and/or depressive-like behaviours are also present. Anxiety-like responses are not evident in young Cpefat/fat mice (∼60 d), but appear in older animals (>90 d). These behaviours are reversed by acute treatment with diazepam or fluoxetine. In contrast, increased immobilities in forced swim and tail suspension are evident in all age groups examined. These behaviours are reversed by acute administration of reboxetine. In comparison acute treatments with fluoxetine or bupropion are ineffective; however, immobility times are normalized with 2 wk treatment. These data demonstrate that Cpefat/fat mice display depressive-like responses aged ∼60 d, whereas anxiety-like behaviours emerge ∼1 month later. In tail suspension, the reboxetine findings show that noradrenergic actions of antidepressants are intact in Cpefat/fat mice. The ability of acute fluoxetine treatment to rescue anxiety-like while leaving depressive-like responses unaffected suggests that serotonin mechanisms underlying these behaviours are different. Since depressive-like responses in the Cpefat/fat mice are rescued by 2 wk, but not acute, treatment with fluoxetine or bupropion, these mice may serve as a useful model that resembles human depression.
Sex attraction studies were carried out to investigate the mate-finding behaviour of invasive Vespula vulgaris (Linnaeus) (Hymenoptera: Vespidae) wasps. Delta traps were baited with live, caged males, and gynes (virgin queens) of V. vulgaris to determine whether either sex produced a long-range sex attractant. Traps baited with gynes caught 71 males, while the controls and live-male wasp baited traps did not catch gynes. Wind tunnel trials were performed to verify if the signal produced by the gynes was chemical in nature. First, V. vulgaris males were flown to live caged gynes, where more than half of the males tested flew upwind in a zigzagging pattern and made contact with caged gynes. Males were also flown to hexane rinses of gynes and flew upwind in a zigzagging pattern towards the gyne extract, although none made contact with the cotton roll stimulus. The results presented here demonstrate conclusively that V. vulgaris gynes produce a sex pheromone.
The scientific literature contains evidence suggesting that women who have been treated for breast cancer may, as a result of their diagnosis, increase their phyto-oestrogen (PE) intake. In the present paper, we describe the creation of a dietary analysis database (based on Dietplan6) for the determination of dietary intakes of specific PE (daidzein, genistein, glycitein, formononetin, biochanin A, coumestrol, matairesinol and secoisolariciresinol), in a group of women previously diagnosed and treated for postmenopausal breast cancer. The design of the database, data evaluation criteria, literature data entry for 551 foods and primary analysis by LC–MS/MS of an additional thirty-four foods for which there were no published data are described. The dietary intake of 316 women previously treated for postmenopausal breast cancer informed the identification of potential food and beverage sources of PE and the bespoke dietary analysis database was created to, ultimately, quantify their PE intake. In order that PE exposure could be comprehensively described, fifty-four of the 316 subjects completed a 24 h urine collection, and their urinary excretion results allowed for the description of exposure to include those identified as ‘equol producers’.